University of Wisconsin Hematology

Thrombosis

VTE

Venous thromboembolism – general, risk factors

  1. Khan et al. Venous thromboembolism. Lancet 2021;398:64
  2. Akpan and Hunt. How I approach the prevention and treatment of thrombotic complications in hospitalized patients. Blood 2023;142:769
  3. Di Nisio et al. Deep vein thrombosis and pulmonary embolism. Lancet 2016;388:3060
  4. Morillo et al. DVT Management and Outcome Trends, 2001 to 2014. Chest 2016;150:374
  5. Chopard et al. Diagnosis and Treatment of Lower Extremity Venous Thromboembolism. A Review, JAMA 2020;324:1765
  6. Zakai et al. Racial and Regional Differences in Venous Thromboembolism in the United States in 3 Cohorts. Circulation 2014;129:1502(With editorial)
  7. van Langevelde et al. Broadening the factor V Leiden paradox: pulmonary embolism and deep-vein thrombosis as 2 sides of the spectrum. Blood 2012;120:933(Differences in risk factors for DVT and PE)
  8. Rosendaal F. Venous Thrombosis: The Role of Genes, Environment, and Behavior. Hematology 2005:1-12.
  9. Najem et al. Cytokine and chemokine regulation of venous thromboembolism. J Thromb Haemost 2020;18:1009
  10. Kearon et al. Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH. J Thromb Haemost 2016;14:1480
  11. Khorana et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008;111:4902
  12. Kearon C. Natural history of venous thromboembolism.  Circulation 2003;107:1-22
  13. Mearns et al. Index clinical manifestation of venous thromboembolism predicts early recurrence type and frequency: a meta-analysis of randomized controlled trials. J Thromb Haemost 2015;13:1043(Most recurrent VTE events of the same type – DVT vs PE – as index event; in PE patients, case-fatality rate for recurrent events 41%)
  14. Alving et al. Consultations on Patients with Venous or Arterial Diseases. Hematology 2003:540-558
  15. Dobromirski and Cohen. How I manage venous thromboembolism risk in hospitalized medical patients. Blood 2012;120:1562
  16. Darzi et al. Prognostic factors for VTE and bleeding in hospitalized medical patients: a systematic review and meta-analysis. Blood 2020;135:1788
  17. Bruno et al. Venous thrombosis risk during and after medical and surgical hospitalizations: The medical inpatient thrombosis and hemostasis (MITH) study. J thromb Haemost 2022;20:1645 (VTE risk markedly higher in first 3 months post discharge)
  18. Roach et al. Differential risks in men and women for first and recurrent venous thrombosis: the role of genes and environment. J Thromb Haemost 2014;12:1593
  19. Pomp et al. Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations. Br J Haematol 2007;139:289(2.4 fold increased risk of VTE in obesity, 24-fold increase in obese women using OC)
  20. Parkin et al. Body Mass Index, Surgery, and Risk of Venous Thromboembolism in Middle-Aged Women. A Cohort Study. Circulation 2012;125:1897(VTE risk increases with increasing BMI, particularly after surgery)
  21. Holst et al. Risk factors for venous thromboembolism. Results from the Copenhagen City Heart Study. Circulation 2010;121:1896(Obesity and smoking, but not dyslipidemia or diabetes, increased risk of VTE)
  22. Sweetland et al. Smoking, Surgery, and Venous Thromboembolism Risk in Women. United Kingdom Cohort Study. Circulation 2013;127:1276
  23. Enga et al. Cigarette smoking and the risk of venous thromboembolism: The Tromsø Study. J Thromb Haemost 2012;10:2068(Heavy smoking a modest risk factor for VTE)
  24. Rogers et al. Triggers of hospitalization for venous thromboembolism. Circulation 2012;125:2092(Infection, treatment with erythropoiesis-stimulating agents, and transfusion identified as possible triggers for VTE)
  25. Ocak et al. Risk of venous thrombosis in patients with major illnesses: results from the MEGA study. J Thromb Haemost 2013;11:116(Major illness + immobilization or thrombophilia → high risk)
  26. Klok et al. Risk of arterial cardiovascular events in patients after pulmonary embolism. Blood 2009;114:1484 (2-fold increased risk of arterial events following unprovoked PE)
  27. Green D. Risk of future arterial cardiovascular events in patients with idiopathic venous thromboembolism. Hematology 2009;259
  28. Huerta et al. Risk Factors and Short-term Mortality of Venous Thromboembolism Diagnosed in the Primary Care Setting in the United Kingdom. Arch Intern Med 2007;167:935
  29. Naess et al. Incidence and mortality of venous thrombosis: a population‐based study. J Thromb Haemost 2007;5:692
  30. Spencer et al. Venous thromboembolism in the outpatient setting. Arch Intern Med 2007;167:1471(More VTEs diagnosed in the 3 months after hospitalization than during hospitalization, suggesting need for extended prophylaxis)
  31. Spencer et al. Patient Outcomes After Deep Vein Thrombosis and Pulmonary Embolism. The Worcester Venous Thromboembolism Study. Arch Intern Med 2008;168:425(Patients with PE had higher mortality, but similar rate of subsequent PE as patients with DVT; 5 year recurrence rate about 5% in both groups)
  32. Palareti and Schellong. Isolated distal deep vein thrombisis: what we know and what we are doing. J Thromb Haemost 2012;10:11
  33. Palareti G. How I treat isolated distal deep vein thrombosis (IDDVT). Blood 2014;123:1802
  34. Silverstein et al. Venous thrombosis in the elderly: more questions than answers. Blood 2007;110:3097
  35. Sweetland et al. Duration and magnitude of the postoperative risk of venous thromboembolism in middle aged women: prospective cohort study. BMJ 2009;339:b4583(70-fold increased risk of VTE in 12 weeks after surgery; highest risk after hip, knee or cancer surgery)
  36. Barbar et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 2010;8:2450
  37. Januel et al. Symptomatic In-Hospital Deep Vein Thrombosis and Pulmonary Embolism Following Hip and Knee Arthroplasty Among Patients Receiving Recommended Prophylaxis: A Systematic Review. JAMA 2012;307:294(VTE rate about 1% for knee replacement, about 0.5% for hip replacement if LMWH or direct IIa or Xa inhibitor given)
  38. Dahl and Borris. Thromboembolism in major joint prosthetic surgery: False or fact. J Thromb Haemost 2019;17:1623
  39. van Adrichem et al. Risk of venous thrombosis after arthroscopy of the knee: results from a large population-based case–control study. J Thromb Haemost 2015;13:1441(18-fold increased VTE risk in first 3 mo after arthroscopy)
  40. Simon et al. Venous Thromboembolism in Total Hip and Total Knee Arthroplasty. JAMA Netw Open. 2023;6(12):e2345883 (ASA and DOACs equally effective prophylaxis; more bleeding with DOACs)
  41. Bouyer et al. Thromboembolic risk after lumbar spine surgery: a cohort study on 325 000 French patients. J Thromb Haemost 2018;16:1537(Overall risk <1%; higher risk with more invasive procedures)
  42. Engbers et al. The contribution of immobility risk factors to the incidence of venous thrombosis in an older population. J Thromb Haemost 2014;12:290
  43. Nemeth et al. High risk of recurrent venous thrombosis in patients with lower‐leg cast immobilization. J Thromb Haemost 2018;16:2218(3.2% VTE incidence within 3 mo)
  44. Houghton et al. Reduced calf muscle pump function is a risk factor for venous thromboembolism: a population-based cohort study. Blood 2021;137:3284
  45. Tang et al. Heart failure and risk of venous thromboembolism: a systematic review and meta-analysis. Lancet Haematol 2016;3:e30(Hospitalized patients with heart failure have a 1.5-fold increased risk of VTE)
  46. White et al. Incidence of Venous Thromboembolism in the Year Before the Diagnosis of Cancer in 528 693 Adults. Arch Intern Med 2005;165:1782
  47. Dennis et al. The timing, extent, progression and regression of deep vein thrombosis in immobile stroke patients: observational data from the CLOTS multicenter randomized trials. J Thromb Haemost 2011;9:2193(15% had a DVT within a month of stroke; most asymptomatic)
  48. Tøndel et al. Risk factors and predictors for venous thromboembolism in people with ischemic stroke: A systematic review. J Thromb Haemost 2022;20:2173
  49. Mauck et al. Incidence of venous thromboembolism after elective knee arthroscopic surgery: a historical cohort study. J Thromb Haemost 2013;11:1279(0.4% incidence of VTE after 35 days; higher incidence in older or hospitalized pts)
  50. Geerts et al.  A prospective study of venous thromboembolism after major trauma.  NEJM 1994;331:1601
  51. Chandra et al. Meta-analysis: travel and risk for venous thromboembolism. Ann Intern Med 2009;151:180 (VTE risk increases by 26% for each 2-hour increment in air travel duration; overall 3-fold increased VTE risk with travel by any mode)
  52. MacCallum et al. Cumulative flying time and risk of venous thromboembolism. Br J Haematol 2011;155:613.(Cumulative flying time of over 12 h in a 4-week period increased VTE risk 3-fold)
  53. Cannegieter et al. Travel-Related Venous Thrombosis: Results from a Large Population-Based Case Control Study (MEGA Study). PLoS Med 2006; e307(“risk of venous thrombosis is moderately increased for all modes of travel””)
  54. Kuipers et al. The Absolute Risk of Venous Thrombosis after Air Travel: A Cohort Study of 8,755 Employees of International Organisations. PLoS 2007;4:e290
  55. Chang et al. Association of Varicose Veins With Incident Venous Thromboembolism and Peripheral Artery Disease. JAMA 2018;319:807(5-fold higher DVT incidence in patients with varicose veins)
  56. van Stralen et al. Minor injuries as a risk factor for venous thrombosis. Arch Intern Med 2008;168:21(Minor leg injuries increased risk of DVT within subsequent 10 weeks; FVL + leg injury → 50x increased risk)
  57. Smeets et al. The risk of venous thromboembolism after minor surgical procedures: A population-based case-control study. J Thromb Haemost 2023;21:975 (3.5-fold increase in VTE risk in first 90 days; absolute risk low)
  58. Mahmoodi et al. Microalbuminuria and Risk of Venous Thromboembolism. JAMA 2009;301:1790
  59. Mahmoodi et al. Association of Mild to Moderate Chronic Kidney Disease With Venous Thromboembolism. Pooled Analysis of Five Prospective General Population Cohorts. Circulation 2012;126:1964
  60. van Zaane et al. Increasing levels of free thyroxine as a risk factor for a first venous thrombosis: a case-control study. Blood 2010:115:4344
  61. Debeij et al. High levels of procoagulant factors mediate the association between free thyroxine and the risk of venous thrombosis: the MEGA study. J Thromb Haemost 2014;12:839
  62. Johannesdottir et al. Use of Glucocorticoids and Risk of Venous Thromboembolism. A Nationwide Population-Based Case-Control Study. JAMA Intern Med 2013;173:743(Increased VTE risk with oral or inhaled steroids)
  63. Walker et al. Association of Testosterone Therapy With Risk of Venous Thromboembolism Among Men With and Without Hypogonadism. JAMA Intern Med 2020;180:190(Testosterone therapy increases VTE risk ~2-fold in men with and without hypogonadism)
  64. Baillargeon et al. Risk of venous thromboembolism in men receiving testosterone therapy. Mayo Clin Proc 2015;90:1038(No apparent increase in VTE risk with testosterone)
  65. Roetker et al. Taller height as a risk factor for venous thromboembolism: a Mendelian randomization meta-analysis. J Thromb Haemost 2017;15:1334(Risk of VTE, especially DVT, increases by 30-40% for each 10 cm increment in height)
  66. Harbin and Lutsey. May‐Thurner syndrome: History of understanding and need for defining population prevalence. J Thromb Haemost 2020;18:534
  67. Manco-Johnson M. How I treat venous thrombosis in children. Blood 2006;107:21

Pulmonary embolism

  1. Kahn and de Wit. Pulmonary Embolism. NEJM 2022;387:58
  2. Peacock and Singer. Reducing the hospital burden associated with the treatment of pulmonary embolism. J Thromb Haemost 2019;17:720
  3. Fang et al. Outcomes in Adults With Acute Pulmonary Embolism Who Are Discharged From Emergency Departments. The Cardiovascular Research Network Venous Thromboembolism Study. JAMA Intern Med 2015;175:1060
  4. Farmakis et al. Functional capacity and dyspnea during follow-up after acute pulmonary embolism. J Thromb Haemost 2024;22:163 (20% of PE patients have persistent loss of functional capacity)
  5. Bastas et al. Long-term outcomes of pulmonary embolism in children and adolescents. Blood 2024;143:631 (CTEPH uncommon; most post-PE exercise limitation due to deconditioning)
  6. Wood K. Major Pulmonary Embolism. Review of a Pathophysiologic Approach to the Golden Hour of Hemodynamically Significant Pulmonary Embolism. Chest 2002;121:877
  7. de Wit and D’Arsigny. Risk stratification of acute pulmonary embolism. J Thromb Haemost 2022;21:3016
  8. Smith et al. Early anticoagulation is associated with reduced mortality for acute pulmonary embolism. Chest 2010;137:1382(Starting heparin in ED, achieving therapeutic aPTT within 24h both associated with better outcomes)
  9. Kucher et al. Massive pulmonary embolism. Circulation 2006;113:577  (Thrombolysis did not reduce mortality or recurrent PE at 90 days; IVC filter placement associated with improved 90-day survival in this retrospective study)
  10. Laporte et al. Clinical Predictors for Fatal Pulmonary Embolism in 15 520 Patients With Venous Thromboembolism. Findings From the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry. Circulation 2008;117:1711
  11. Raja et al. Evaluation of Patients With Suspected Acute Pulmonary Embolism: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med 2015;163:701
  12. Couteraud et al. Prevalence of Pulmonary Embolism Among Patients With COPD Hospitalized With Acutely Worsening Respiratory Symptoms. JAMA 2021;325:59(PE in about 6%)
  13. Penaloza et al. Pulmonary embolism rule-out criteria (PERC) rule in European patients with low implicit clinical probability (PERCEPIC): a multicentre, prospective, observational study. Lancet Haematol 2017;4:e615
  14. Alkinj et al. Saddle vs Nonsaddle Pulmonary Embolism: Clinical Presentation, Hemodynamics, Management, and Outcomes. Mayo Clin Proc 2017;92:1511 (No difference in short term outcomes between these entities)
  15. Wiener et al. Time Trends in Pulmonary Embolism in the United States. Evidence of Overdiagnosis. Arch Intern Med 2011;171:831(CT angio finds more PE, but with minimal decrease in PE mortality and increased complications from anticoagulation)
  16. Weiner et al. When a test is too good: how CT pulmonary angiograms find pulmonary emboli that do not need to be found. BMJ 2013;347: f3368(80% rise in incidence of PE since 1998 with minimal decrease in mortality suggests that many clinically unimportant emboli are being found with newer imaging techniques)
  17. den Exter et al. Risk profile and clinical outcome of symptomatic subsegmental acute pulmonary embolism. Blood 2013;122:1144(SSPE similar to more proximal clots with respect to risk profile and clinical outcome)
  18. Le Gal et al. Risk for Recurrent Venous Thromboembolism in Patients With Subsegmental Pulmonary Embolism Managed Without Anticoagulation. A Multicenter Prospective Cohort Study. Ann Intern Med 2022;175:29 (292 patients with subsegmental PE but no proximal DVT were not anticoagulated; 3.1% VTE recurrence within 90 days, no fatalities)
  19. O’Connell C. How I treat incidental pulmonary embolism. Blood 2015;125:1877
  20. Rizkallah et al. Prevalence of Pulmonary Embolism in Acute Exacerbations of COPD. A Systematic Review and Metaanalysis. Chest 2009;135:786 (one in four COPD patients hospitalized for acute exacerbation may have PE)
  21. Aleva et al. Prevalence and Localization of Pulmonary Embolism in Unexplained Acute Exacerbations of COPD. A Systematic Review and Meta-analysis. Chest 2017;151:544(PE found in about 16% of patients with unexplained acute exacerbations of COPD)
  22. Prandoni et al. Prevalence of Pulmonary Embolism among Patients Hospitalized for Syncope. NEJM 2016;375:1524(17%)
  23. Costantino et al. Prevalence of Pulmonary Embolism in Patients With Syncope. JAMA Intern Med 2018;178:356(Much lower prevalence than found in Prandoni study)
  24. Prandoni et al. Prevalence of pulmonary embolism among patients with recent onset of dyspnea on exertion. A cross-sectional study. J Thromb Haemost 2023;21:68 (32% had PE; among those with no other findings to suggest PE incidence was about 20%)
  25. Fernandes et al. Anticoagulation for Subsegmental Pulmonary Embolism. NEJM 2019;381:1171(Arguments for and against)
  26. Ro et al. Autopsy-proven untreated previous pulmonary thromboembolism: frequency and distribution in the pulmonary artery and correlation with patients’ clinical characteristics. J Thromb Haemost 2011;9:922(Over 90% of patients dying of PE had evidence of previous emboli)
  27. Kline et al. Prospective Evaluation of Right Ventricular Function and Functional Status 6 Months After Acute Submassive Pulmonary Embolism. Frequency of Persistent or Subsequent Elevation in Estimated Pulmonary Artery Pressure. Chest 2009;136:1202(About 7% of patients getting heparin had elevated RV pressure after 6 mo, vs 11% who got thrombolytic therapy)
  28. Alonso-Fernández et al. Association Between Obstructive Sleep Apnea and Pulmonary Embolism. Mayo Clin Proc 2013;88:579(OSA prevalence increased in patients with PE)
  29. Enga et al. Atrial fibrillation and future risk of venous thromboembolism:the Tromsø study. J Thromb Haemost 2015;13:10(Increased PE risk, possibly from RA thrombi)
  30. Le Moigne et al. Patent Foramen Ovale and Ischemic Stroke in Patients With Pulmonary Embolism: A Prospective Cohort Study. Ann Intern Med 2019;170:756(Stroke 4X more common in PE patients with PFO than those without)
  31. Poterucha et al. Surgical pulmonary embolectomy. Circulation 2015;132:1146
  32. Martillotti et al. Treatment options for severe pulmonary embolism during pregnancy and the postpartum period: a systematic review. J Thromb Haemost 2017;15:1942

Diagnosis of venous thromboembolism

  1. Lim et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism. Blood Adv 2018;2:3226
  2. Needleman et al. Ultrasound for Lower Extremity Deep Venous Thrombosis. Multidisciplinary Recommendations From the Society of Radiologists in Ultrasound Consensus Conference. Circulation 2018;137:1505
  3. Wells et al. Diagnosis of Venous Thromboembolism: 20 Years of Progress. Ann Intern Med 2018;168:131
  4. Huisman and Klok. Current challenges in diagnostic imaging of venous thromboembolism. Blood 2015;126:2376
  5. Dronkers et al. Current and future perspectives in imaging of venous thromboembolism. J Thromb Haemost 2016;14:1696
  6. Huisman and Klok. Diagnostic management of acute deep vein thrombosis and pulmonary embolism. J Thromb Haemost 2013;11:412
  7. Wells et al. Accuracy of clinical assessment of deep-vein thrombosis. Lancet 1995;345:1326(The “Wells score” for determining pre-test probability of DVT)
  8. Silveira et al. Performance of Wells Score for Deep Vein Thrombosis in the Inpatient Setting. JAMA Intern Med 2015;175:1112(Wells score less useful in predicting DVT for inpatients)
  9. Büller et al. Safely Ruling Out Deep Venous Thrombosis in Primary Care. Ann Intern Med 2009;150:229
  10. Johnson et al. Risk of Deep Vein Thrombosis Following a Single Negative Whole-Leg Compression Ultrasound. A Systematic Review and Meta-analysis. JAMA 2010; 303:438(0.6% of patients with negative US have VTE in next 3 months)
  11. van Dam et al. Magnetic resonance imaging for diagnosis of recurrent ipsilateral deep vein thrombosis. Blood 2020;135:1377
  12. Tan et al. Magnetic resonance direct thrombus imaging differentiates acute recurrent ipsilateral deep vein thrombosis from residual thrombosis. Blood 2014;124:623
  13. van Dam et al. Detection of upper extremity deep vein thrombosis by magnetic resonance non-contrast thrombus imaging. J Thromb Haemost 2021;19:1973(93% sensitive, 100% specific)
  14. Stein et al. D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism.  A systematic review.  Ann Intern Med 2004;140:589
  15. Prandoni et al. D‐dimer as an adjunct to compression ultrasonography in patients with suspected recurrent deep vein thrombosis. J Thromb Haemost 2007;5:1076
  16. van der Hulle et al. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet 2017;390:289(Using higher D-dimer cutoff for patients with lower clinical suspicion of PE is safe, leads to fewer CT scans being done)
  17. Kearon et al. A Randomized Trial of Diagnostic Strategies after Normal Proximal Vein Ultrasonography for Suspected Deep Venous Thrombosis: D-Dimer Testing Compared with Repeated Ultrasonography. Ann Intern Med 2005;142:490
  18. Bernardi et al. Serial 2-Point Ultrasonography Plus D-Dimer vs Whole-Leg Color-Coded Doppler Ultrasonography for Diagnosing Suspected Symptomatic Deep Vein Thrombosis. A Randomized Controlled Trial. JAMA 2008;300:1653(proximal US + D-dimer equivalent to whole leg US)
  19. Linkins et al. Selective D-Dimer Testing for Diagnosis of a First Suspected Episode of Deep Venous Thrombosis: A Randomized Trial. Ann Intern Med 2013;158:93(Suggests that US without D-Dimer testing more cost-effective for inpatients or outpts with high pretest probability of DVT)
  20. Chan et al. Lack of consistency in the relationship between asymptomatic DVT detected by venography and symptomatic VTE in thromboprophylaxis trials. Thromb Haemost 2015;114:1049(Venography-diagnosed DVT 10-20x more prevalent than symptomatic DVT)
  21. Mumoli et al. Ultrasound elastography is useful to distinguish acute and chronic deep vein thrombosis. J Thromb Haemost 2018;16:2482
  22. Righini et al. Diagnosis of acute pulmonary embolism. J Thromb Haemost 2017;15:1251
  23. Huisman and Klock. How I diagnose acute pulmonary embolism. Blood 2013;121:4443
  24. Perrier et al.  Cost-effectiveness analysis of diagnostic strategies for suspected pulmonary embolism including helical computed tomography. Am J Respir Crit Care Med 2003;167:39
  25. Stals et al. Safety and Efficiency of Diagnostic Strategies for Ruling Out Pulmonary Embolism in Clinically Relevant Patient Subgroups. A Systematic Review and Individual-Patient Data Meta-analysis. Ann Intern Med 2022;175:244 (Raising D-dimer threshold for older patients or those with acute medical illness lowers sensitivity; with useful editorial)
  26. Freund et al. Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients. The PROPER Randomized Clinical Trial. JAMA 2018;319:559(Clinical criteria can be safely used to rule out PE in very low risk patients without further testing)
  27. PIOPED Investigators. Value of the Ventilation/Perfusion Scan in Acute Pulmonary Embolism Results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). JAMA 1990;263:2753(High probability scans had good specificity but low sensitivity; overall specificity very low)
  28. Stein et al. Multidetector Computed Tomography for Acute Pulmonary Embolism. NEJM 2006;354:2317(PIOPED II study)
  29. Robert-Ebadi et al. Safety of multidetector computed tomography pulmonary angiography to exclude pulmonary embolism in patients with a likely pretest clinical probability. J Thromb Haemost 2017;15:1584(0.6% of untreated patients with negative CTPA had VTE within next 3 mo)
  30. Carrier et al. Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies. J Thromb Haemost 2010;8:1716(“Subsegmental PE may not be clinically relevant”)
  31. Kearon et al. An Evaluation of D-Dimer in the Diagnosis of Pulmonary Embolism. Ann Intern Med 2006;144:812
  32. Anderson et al. Computed Tomographic Pulmonary Angiography vs Ventilation-Perfusion Lung Scanning in Patients With Suspected Pulmonary Embolism. JAMA 2007;2743(CT more sensitive than VQ scan, but may give more false positive results)
  33. Wiener et al. Time Trends in Pulmonary Embolism in the United States. Evidence of Overdiagnosis. Arch Intern Med 2011;171:831(CT angio finds more PE, but with minimal decrease in PE mortality and increased complications from anticoagulation)
  34. Weiner et al. When a test is too good: how CT pulmonary angiograms find pulmonary emboli that do not need to be found. BMJ 2013;347: f3368(80% rise in incidence of PE since 1998 with minimal decrease in mortality suggests that many clinically unimportant emboli are being found with newer imaging techniques)
  35. Righini et al. Diagnosis of Pulmonary Embolism During Pregnancy: A Multicenter Prospective Management Outcome Study. Ann Intern Med 2018;169:766
  36. van der Pol et al. Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism. NEJM 2019;380:1139
  37. Stals et al. Noninvasive diagnostic work-up for suspected acute pulmonary embolism during pregnancy: a systematic review and meta-analysis of individual patient data. J Thromb Haemost 2023;21:606
  38. Moody A.  Magnetic resonance direct thrombus imaging. J Thromb Haemos 2003;1:1403

Treatment of acute venous thromboembolism

  1. Kearon C. A conceptual framework for two phases of anticoagulant treatment of venous thromboembolism. J Thromb Haemost 2012;10:507(Evidence supporting a standard treatment duration of 3 months)
  2. Becattini and Agnelli. Acute treatment of venous thromboembolism. Blood 2020;135:305
  3. Jain and Cifu. Antithrombotic Therapy for Venous Thromboembolic Disease. JAMA 2017;317:2008
  4. Kearon et al. Antithrombotic therapy for VTE disease. Chest 2016;149:315
  5. Kearon and Akl. Duration of anticoagulant therapy for deep vein thrombosis and pulmonary embolism. Blood 2014;123:1794
  6. Bistervels et alSex matters: Practice 5P’s when treating young women with venous thromboembolism. J Thromb Haemost 2019;17:1417
  7. Kearon et al. Antithrombotic Therapy for VTE Disease : CHEST Guideline and Expert Panel Report. Chest 2016;149:315(Update of 2012 guidelines)
  8. Baglin et al. Duration of anticoagulant therapy after a first episode of an unprovoked pulmonary embolus or deep vein thrombosis: guidance from the SSC of the ISTH. J Thromb Haemost 2012;10:698
  9. Ageno et al. Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomised controlled trial. BMJ 2022;379:e072623 (Recurrence/progression rate 19% with six-week treatment, 11% with 3 month treatment)
  10. Castellucci et al. Clinical and Safety Outcomes Associated With Treatment of Acute Venous Thromboembolism. A Systematic Review and Meta-analysis. JAMA 2014;312:1122(UFH/VKA inferior to LMWH/VKA; rivaroxaban and apixaban appear safer than other treatments)
  11. Matisse Investigators. Subcutaneous Fondaparinux versus Intravenous Unfractionated Heparin in the Initial Treatment of Pulmonary Embolism. NEJM 2003;349:1695
  12. Hull et al.  Heparin for 5 days compared with 10 days in the initial treatment of proximal venous thrombosis.  NEJM 1990;322:1260
  13. Brandjes et al.  Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal vein thrombosis.  NEJM 1992;327:1485
  14. Hull et al.  Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis.  NEJM 1986;315:1109
  15. Heit et al. Heparin and warfarin anticoagulation intensity as predictors of recurrence after deep vein thrombosis or pulmonary embolism: a population-based cohort study. Blood 2011;118:4992(Lower-intensity heparin + standard warfarin therapy effective in preventing recurrence)
  16. Levine et al.  A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis.  NEJM 1996;334:677
  17. Quinlan et al. Low-Molecular-Weight Heparin Compared with Intravenous Unfractionated Heparin for Treatment of Pulmonary Embolism. A Meta-Analysis of Randomized, Controlled Trials.  Ann Intern Med 2004;140:175
  18. Kearon et al.  Comparison of Fixed-Dose Weight-Adjusted Unfractionated Heparin and Low-Molecular-Weight Heparin for Acute Treatment of Venous Thromboembolism. JAMA 2006;296:935(unfractionated heparin as effective as LMWH)
  19. Righini et al. Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial. Lancet Haematol 2016;3:e556(Nadroparin-treated patients had modest, non-significant decrease in clot progression vs placebo, with more bleeding)
  20. Righini et al. Effect of anticoagulant treatment on pain in distal deep vein thrombosis: an ancillary analysis from the cactus trial. J Thromb Haemost 2019;17:507(Post hoc analysis of above trial did not show any benefit of LMWH for pain control)
  21. Franco et al. Anticoagulation in patients with isolated distal deep vein thrombosis: a meta-analysis. J Thromb Haemost 2017;15:1142(Anticoagulation reduced PE risk from 2.4% to 1.4%; treatment duration of at least 6 weeks most effective)
  22. Merriman et al. Two Weeks of Low Molecular Weight Heparin for Isolated Symptomatic Distal Vein Thrombosis (TWISTER study). Thromb Res 2021;207:33(Safe to stop anticoagulation after 2 weeks if symptoms gone and US shows no clot extension)
  23. Ageno et al. Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomised controlled trial. BMJ 2022;379:e072623 (Fewer complications with 3 months of treatment vs 6 weeks)
  24. Bates and Ginsberg.  How we manage venous thromboembolism during pregnancy.  Blood 2002;100:3470
  25. Prandoni P. How I treat venous thromboembolism in patients with cancer. Blood 2005;106:4027
  26. Kyrle PA. How I treat recurrent deep-vein thrombosis. Blood 2016;127:696
  27. Goy et al. Sub-segmental pulmonary embolism in three academic teaching hospitals: a review of management and outcomes. J Thromb Haemost 2015;13:214(No recurrent clots in patients with SSPE whether or not they were anticoagulated)
  28. Comerota et al. Endovascular Thrombus Removal for Acute Iliofemoral Deep Vein Thrombosis. Analysis From a Stratified Multicenter Randomized Trial. Circulation 2019;139:1162 (Embolectomy did not reduce VTE recurrence rate but did lessen severity of post-thrombotic symptoms. With editorial)
  29. Sareyyupoglu et al. A More Aggressive Approach to Emergency Embolectomy for Acute Pulmonary Embolism. Mayo Clin Proc 2010;85:785
  30. Korayem et al. Real-World Evaluation of the Safety and Effectiveness of Apixaban & Rivaroxaban Lead-in Dosing Compared to Parenteral Lead-in Dosing in the Treatment of Venous Thromboembolism: A Multi-Center Retrospective Cohort Study. Int J Gen Med 2023;16:129 (More bleeding, more recurrent events with parenteral lead-in)
  31. May and Moll. How I treat the co-occurrence of venous and arterial thromboembolism: anticoagulation, antiplatelet therapy, or both? Blood 2024;143:2351

Thrombolytic treatment of venous thromboembolism

  1. Wang et al. The role of thrombolytic therapy in pulmonary embolism. Blood 2015;125:2191
  2. Chatterjee et al. Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality, Major Bleeding, and Intracranial Hemorrhage. A Meta-analysis. JAMA 2014;311:2414(Lower mortality, more bleeding and intracranial hemorrhage with thrombolysis in patients with hemodynamic instability or RV dysfunction; with editorial)
  3. Perlroth et al. Effectiveness and Cost-effectiveness of Thrombolysis in Submassive Pulmonary Embolism. Arch Intern Med 2007;167:74
  4. Meyer et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. NEJM 2014;370:1402(Thrombolytic Rx decreased risk of hemodynamic decompensation, increased risk of major bleeding & stroke; with editorial)
  5. Nakamura et al. Impact of the efficacy of thrombolytic therapy on the mortality of patients with acute submassive pulmonary embolism: a meta-analysis. J Thromb Haemost 2014;12:1086(Thrombolytic Rx did not lower mortality but did lower risk of clinical deterioration)
  6. Kline et al. Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double-blind, placebo-controlled randomized trial. J Thromb Haemost 2014;12:459(Better outomes with thrombolysis)
  7. Kucher et al. Randomized, Controlled Trial of Ultrasound-Assisted Catheter-Directed Thrombolysis for Acute Intermediate-Risk Pulmonary Embolism. Circulation 2014;129:479(More rapid hemodynamic improvement with thrombolysis, no increased bleeding)
  8. Sharifi et al. Moderate Pulmonary Embolism Treated With Thrombolysis (from the “MOPETT” Trial). Am J Cardiol 2013;111:273(A lower dose of TPA reduced pulmonary pressures quickly, did not cause bleeding; trend towards better survival vs placebo)
  9. Vedantham S. Endovascular procedures in the management of DVT. Hematology 2011:156
  10. Vedantham and Sista. How I use catheter-directed interventional therapy to treat patients with venous thromboembolism. Blood 2018;131:733
  11. Haig et al. Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. Lancet Haematol 2016;3:e64 (28% lower risk of PTS in patients treated with thrombolysis; no difference in QOL scores, however. With editorial)
  12. Bashir et al. Comparative Outcomes of Catheter-Directed Thrombolysis Plus Anticoagulation vs Anticoagulation Alone to Treat Lower-Extremity Proximal Deep Vein Thrombosis. JAMA Intern Med 2014;174:1494
  13. Shahjouei et al. Safety of Intravenous Thrombolysis Among Patients Taking Direct Oral Anticoagulants. A Systematic Review and Meta-Analysis. Stroke 2019 (Epub).
  14. Planer et al. Catheter-directed thrombolysis compared with systemic thrombolysis and anticoagulation in patients with intermediate- or high-risk pulmonary embolism: systematic review and network meta-analysis. CMAJ 2023;195:E833 (Catheter-directed treatment associated with better outcomes)

Prophylaxis of venous thromboembolism

  1. Schünemann et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv 2018;2:3198
  2. Kahn et al. Prevention of VTE in Nonsurgical Patients. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e195S
  3. Gould et al. Prevention of VTE in Nonorthopedic Surgical Patients. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e227S
  4. Falck-Ytter et al. Prevention of VTE in Orthopedic Surgery Patients Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e278S
  5. Klemen et al. Mortality risk associated with venous thromboembolism: a systematic review and Bayesian meta-analysis. Lancet Haematol 2020;7:e583(Finds no evidence of mortality benefit from VTE prophylaxis)
  6. Sobieraj et al. Prolonged Versus Standard-Duration Venous Thromboprophylaxis in Major Orthopedic Surgery. A Systematic Review. Ann Intern Med 2012;156:720
  7. Heit et al. Effect of a near-universal hospitalization-based prophylaxis regimen on annual number of venous thromboembolism events in the US. Blood 2017;130:109(No change in VTE rates between 2005 and 2010 despite near-universal prophylaxis, possibly due to short duration of prophylaxis)
  8. Kapoor et al. Comparative effectiveness of venous thromboembolism prophylaxis options for the patient undergoing total hip and knee replacement: a network meta-analysis. J Thromb Haemost 2017;15:284(Direct Xa inhibitors prevent 4 times as many symptomatic DVTs as LMWH, without an increased bleeding risk)
  9. Qaseem et al. Venous Thromboembolism Prophylaxis in Hospitalized Patients: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med 2011;155:625
  10. Dobromirski and Cohen. How I manage venous thromboembolism risk in hospitalized medical patients. Blood 2012;120:1562
  11. Selby and Geerts. Prevention of venous thromboembolism: consensus, controversies, and challenges. Hematology 2009;286
  12. Leonardi et al. The Rate of Bleeding Complications After Pharmacologic Deep Venous Thrombosis Prophylaxis. Arch Surg 2006;141:790(“most patients undergoing general surgery can receive pharmacologic prophylaxis safely”)
  13. Dentali et al.  Meta-analysis: Anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients.  Ann Intern Med 2007;146:278
  14. Flanders et al. Hospital Performance for Pharmacologic Venous Thromboembolism Prophylaxis and Rate of Venous Thromboembolism. A Cohort Study. JAMA Intern Med 2014;174:1577(No difference in VTE rates between high-performing and low-performing hospitals; with editorial)
  15. Phung et al. Dosing frequency of unfractionated heparin thrombophrophylaxis. A meta-analysis. Chest 2011;140:374(Twice daily dosing as effective as three times daily)
  16. Kakkar et al. Low-molecular-weight heparin and mortality in acutely ill medical patients. NEJM 2011;365:2463(LMWH prophylaxis did not alter mortality from any cause)
  17. Samama et al.  A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients.  NEJM 1999;341:793
  18. Kakkar et al. Low-molecular-weight heparin and mortality in acutely ill medical patients. NEJM 2011;365:2463(LMWH prophylaxis did not decrease mortality)
  19. Fowler et al. Cost-effectiveness of Dalteparin vs Unfractionated Heparin for the Prevention of Venous Thromboembolism in Critically Ill Patients. JAMA 2014;312:2135(LMWH more effective, lower overall cost due to lower PE and HIT rates)
  20. Paciaroni et al. Efficacy and safety of anticoagulants in the prevention of venous thromboembolism in patients with acute cerebral hemorrhage: a meta-analysis of controlled studies. J Thromb Haemost 2011;9:893(Significant reduction in PE, non-significant decrease in mortality, increased risk of enlarging hematoma)
  21. Gage et al. Effect of Low-Intensity vs Standard-Intensity Warfarin Prophylaxis on Venous Thromboembolism or Death Among Patients Undergoing Hip or Knee ArthroplastyA Randomized Clinical Trial. JAMA 2019;322:834(Target INR 1.8 resulted in higher rate of VTE or death than target 2.5)
  22. Camporese et al. Low-Molecular-Weight Heparin versus Compression Stockings for Thromboprophylaxis after Knee Arthroscopy. A Randomized Trial. Ann Intern Med 2008;149:73(LMWH superior)
  23. van Adrichem et al. Thromboprophylaxis after Knee Arthroscopy and Lower-Leg Casting. NEJM 2017;376:515(No significant benefit from LMWH prophylaxis – incidence of VTE low in both treatment and control groups; with editorial)
  24. Ettema et al. Prevention of venous thromboembolism in patients with immobilization of the lower extremities: a meta-analysis of randomized controlled trials. J Thromb Haemost 2008;6:1093 (40% reduction in VTE risk, no excess bleeding risk with LMWH)
  25. Wein et al. Pharmacological venous thromboembolism prophylaxis in hospitalized medical patients. A meta-analysis of randomized controlled trials. Arch Intern Med 2007;167:1476(Both UFH and LMWH reduce VTE risk; LMWH more effective in preventing DVT)
  26. Hull et al. Extended-Duration Venous Thromboembolism Prophylaxis in Acutely Ill Medical Patients With Recently Reduced Mobility. A Randomized Trial. Ann Intern Med 2010;153:8(Prophylaxis for 28 days vs 10 days reduces VTE more than it increases bleeding in older patients and women)
  27. Chi et al. Effect of extended-duration thromboprophylaxis on venous thromboembolism and major bleeding among acutely ill hospitalized medical patients: a bivariate analysis. J Thromb Haemost 2017;15:1913(Compares safety & efficacy of LMWH vs 3 DOACs)
  28. Cohen et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 2006;332:325
  29. Ageno et al. Safety and efficacy of low-dose fondaparinux (1.5 mg) for the prevention of venous thromboembolism in acutely ill medical patients with renal impairment: the FONDAIR study. J Thromb Haemost 2012;10:2291(Low dose fondaparinux safe and “relatively effective” in patients with CCr between 20 and 50)
  30. Shatzel et al. Safety and efficacy of pharmacological thromboprophylaxis for hospitalized patients with cirrhosis: a single-center retrospective cohort study. J Thromb Haemost 2015;13:1245(Low rate of VTE in hospitalized cirrhotics, not affected by thromboprophylaxis; UFH caused more bleeding than LMWH)
  31. Glynn et al. Effect of low-dose aspirin on the occurrence of venous thromboembolism. Ann Intern Med 2007;147:525(ASA 100 mg qod had no apparent effect on occurence of VTE in women)
  32. Anderson et al. Aspirin Versus Low-Molecular-Weight Heparin for Extended Venous Thromboembolism Prophylaxis After Total Hip Arthroplasty: A Randomized Trial. Ann Intern Med 2013;158:800(ASA as effective as LMWH for extended prophylaxis following 10 days of LMWH)
  33. Matharu et al. Clinical Effectiveness and Safety of Aspirin for Venous Thromboembolism Prophylaxis After Total Hip and Knee Replacement. A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Intern Med 2020;180:376(Safety and efficacy of ASA comparable to other anticoagulants)
  34. Major Extremity Trauma Research Consortium. Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture. NEJM 2023;388:203 (Aspirin non-inferior; with editorial; see also letters to the editor regarding the low-risk trial population and the generalizability of the data)
  35. CRISTAL Study Group. Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty. The CRISTAL Randomized Trial. JAMA 2022;328:719 (Symptomatic VTE rate with ASA 3.45%, vs 1.82% with LMWH)
  36. Roberts et al. Thromboprophylaxis for venous thromboembolism prevention in hospitalized patients with cirrhosis: Guidance from the SSC of the ISTH. J Thromb  Haemost 2022;20:2237
  37. CLOTS Trials Collaboration: Thigh-length versus below-knee stockings for deep venous prophylaxis after stroke. A randomized trial. Ann Intern Med 2010;153:553. (More VTE events in patients using below-knee stockings. See editorialdiscussing this and the previous article)
  38. CLOTS Trials Collaboration. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial. Lancet 2013;382:616(Significant decrease in DVT risk when IPC added to standard thromboprophylaxis)
  39. Arabi et al. Adjunctive Intermittent Pneumatic Compression for Venous Thromboprophylaxis. NEJM 2019;380:1305(No benefit to adding IPC to standard pharmacologic thromboprophylaxix in critically ill patients; with editorial)
  40. Evans and Green. ASH evidence-based guidelines: statins in the prevention of venous thromboembolism. Hematology 2009;273
  41. Kunutsor et al. Statins and primary prevention of venous thromboembolism: a systematic review and meta-analysis. Lancet Haematol 2017;4:e83(25% risk reduction with statins; rosuvastatin appears most effective)
  42. Orsi et al. Rosuvastatin use reduces thrombin generation potential in patients with venous thromboembolism: a randomized controlled trial. J Thromb Haemost 2019;17:319

VTE recurrence risk

  1. Baglin et al. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study.  Lancet 2003;362:523 (Unprovoked VTE has highest recurrence risk; thrombophilia testing not an independent predictor of risk)
  2. Kyrle et al. The long-term recurrence risk of patients with unprovoked venous thromboembolism: an observational cohort study. J Thromb Haemost 2016;14: 2402(Male sex, proximal DVT or PE associated with highest recurrence risk)
  3. Bjøri et al. Hospital-related first venous thromboembolism and risk of recurrence. J Thromb Haemost 2016;14:2368
  4. Tosetto et al. External validation of the DASH prediction rule: a retrospective cohort study. J Thromb Haemost 2017;15:1963(Prediction rule for recurrence of unprovoked VTE)
  5. Alikhan et al. Risk Factors for Venous Thromboembolism in Hospitalized Patients With Acute Medical Illness. Analysis of the MEDENOX Study. Arch Intern Med 2004;164:963
  6. Christiansen et al. Thrombophilia, Clinical Factors, and Recurrent Venous Thrombotic Events.  JAMA. 2005;293:2352(Clinical factors are probably more important than laboratory abnormalities in determining the duration of anticoagulation therapy)
  7. Khan et al. Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis. BMJ 2019;366: I4363(Recurrence risk 10% at 1 year, 25% at 5 years, 36% at 10 years; 4% of recurrences fatal)
  8. Iorio et al. Risk of Recurrence After a First Episode of Symptomatic Venous Thromboembolism Provoked by a Transient Risk Factor. A Systematic Review. Arch Intern Med 2010;170:1710(“The risk of recurrence is low if VTE is provoked by surgery, intermediate if provoked by a nonsurgical risk factor, and high if unprovoked”)
  9. Farren-Dai et al. Association between remote major venous thromboembolism risk factors and the risk of recurrence after a first unprovoked episode. J Thromb Haemost 2017;15:1977(Exposure to potential provoking factor more than 3 mo prior to VTE event did not reduce recurrence risk; such events should be considered unprovoked)
  10. Jørgensen et al. Incidence of bleeding and recurrence in isolated distal deep vein thrombosis: findings from the Venous Thrombosis Registry in Østfold Hospital. J Thromb Haemost 2023;21:2824 (5 and 10 year recurrence rates 14.7% and 27.2% respectively; 29% of recurrences were PE)
  11. Kearon et al. Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial. Blood 2008; 112:4432(single or multiple thrombophilic defects not associated with higher risk of recurrence during warfarin Rx; possible increased risk with APL antibody)
  12. Roach et al. Sex Difference in Risk of Second but Not of First Venous Thrombosis. Paradox Explained. Circulation 2014;129:51(Hormone Rx, pregnancy major contributors to risk of first VTE episode in women; men have 2x higher recurrence risk)
  13. Eichinger et al. Risk Assessment of Recurrence in Patients With Unprovoked Deep Vein Thrombosis or Pulmonary Embolism. The Vienna Prediction Model. Circulation 2010;121:1630(Male sex, proximal DVT or PE, and high D-dimer independent predictors of recurrence)
  14. Roach et al. Sex difference in the risk of recurrent venous thrombosis: a detailed analysis in four European cohorts. J Thromb Haemost 2015;13:1815(Men have 2x higher recurrence risk then women without “reproductive risk factors”)
  15. Tritschler et al. Predicting recurrence after unprovoked venous thromboembolism: prospective validation of the updated Vienna Prediction Model. Blood 2015;126:1949 (Model does not work well in older patients)
  16. Eischer et al. The risk of recurrence in women with venous thromboembolism while using estrogens: a prospective cohort study. J Thromb Haemost 2014;12:635(Low risk of recurrence – 6% in 5 yrs – after stopping anticoagulation)
  17. Aziz et al. Long-term risk of recurrent venous thromboembolism after a first contraceptive-related event: Data from REVERSE cohort study. J Thromb Haemost 2021;19:1526(Recurrence risk 1.1%/pt-yr vs 3.2% for non-OC users)
  18. Wiegers et al. Risk of recurrence in women with venous thromboembolism related to estrogen-containing contraceptives: Systematic review and meta-analysis. J Thromb Haemost 2022;20: 1158 (Low recurrence risk favors short-term anticoagulation)
  19. Palla et al. The clinical course of pulmonary embolism patients anticoagulated for 1 year: results of a prospective, observational, cohort study. J Thromb Haemos 2010;8:68.(9.6% recurrence rate. 80% of recurrences happened within 10 days of dx and 75% of recurrences were fatal)
  20. Douketis et al. The Risk for Fatal Pulmonary Embolism after Discontinuing Anticoagulant Therapy for Venous Thromboembolism. Ann Intern Med 2007;147:766(0.19-0.49 events per 100 person-years)
  21. Palareti et al.  D-dimer testing to determine the duration of anticoagulation therapy. NEJM 2006;355:1780
  22. Verhovsek et al. Systematic Review: D-Dimer to Predict Recurrent Disease after Stopping Anticoagulant Therapy for Unprovoked Venous Thromboembolism. Ann Intern Med 2008;149:481(positive D-dimer associated with 9% annual recurrence risk after stopping treatment, vs 3.5% for negative D-dimer)
  23. Palareti et al. D-dimer to guide the duration of anticoagulation in patients with venous thromboembolism: a management study. Blood 2014;124:196(Negative D-dimer, using age- and gender-specific cutoffs, during and after anticoagulant therapy predicts a lower risk of recurrent VTE after stopping treatment)
  24. Kearon et al. D-Dimer Testing to Select Patients With a First Unprovoked Venous Thromboembolism Who Can Stop Anticoagulant Therapy: A Cohort Study. Ann Intern Med 2015;162:27(Negative D-dimer not sufficient evidence to stop treatment in men with unprovoked VTE; test was helpful in women with estrogen-associated VTE)
  25. Prandoni et al.  The long-term clinical course of acute deep venous thrombosis.  Ann Intern Med 1996;125:1
  26. Seinturier et al. Site and clinical outcome of deep vein thrombosis of the lower limbs: an epidemiological study. J Thromb Haemost 2006;3:1362(Proximal DVT has higher recurrence risk than distal DVT)
  27. Galanaud et al. Incidence and predictors of venous thromboembolism recurrence after a first isolated distal deep vein thrombosis. J Thromb Haemost 2014;12:436(2.7% annualized recurrence rate, vs 5.2% for proximal DVT)
  28. Prandoni et al.  Residual Venous Thrombosis as a Predictive Factor of Recurrent Venous Thromboembolism. Ann Intern Med. 2002;137:955
  29. Siragusa et al. Residual vein thrombosis to establish duration of anticoagulation after a first episode of deep vein thrombosis: the Duration of Anticoagulation based on Compression UltraSonography (DACUS) study. Blood 2008;112:511(absence of residual clot by US associated with low rate of VTE recurrence)
  30. Eichinger et al. Overweight, Obesity, and the Risk of Recurrent Venous Thromboembolism. Arch Intern Med 2008;168:1678(1.6-fold higher recurrence rate in obese individuals)
  31. Stewart and Kline. Metabolic syndrome increases risk of venous thromboembolism recurrence after acute deep vein thrombosis. Blood Adv 2020;4:127
  32. Grifoni et al.Association of Persistent Right Ventricular Dysfunction at Hospital Discharge After Acute Pulmonary Embolism With Recurrent Thromboembolic Events. Arch Intern Med 2006;166:2151
  33. Becattini et al. Risk of recurrent venous thromboembolism after acute pulmonary embolism: Role of residual pulmonary obstruction and persistent right ventricular dysfunction. A meta‐analysis. J Thromb Haemost 2019;17:1217(Residual obstructive detected by lung scan doubles recurrence risk)
  34. Evensen et al. Physical activity and risk of recurrence and mortality after incident venous thromboembolism. J Thromb Haemost 2019;17:901(Physical activity does not lower recurrence risk but does predict lower mortality)

Secondary prevention of venous thromboembolism

  1. Kearon and Kahn. Long-term treatment of venous thromboembolism. Blood 2020;135:317
  2. Rodger and Le Gal. Who should get long-term anticoagulant therapy for venous thromboembolism and with what? Blood Adv 2018;2:3081
  3. Khan et al. Indefinite Anticoagulant Therapy for First Unprovoked Venous Thromboembolism. A Cost-Effectiveness Study. Ann Intern Med 2023;176:949 (Long-term DOAC treatment would prevent about 14 fatal PE events and cause about 11 fatal bleeds per 1000 patients at a cost of about $12000/patient)
  4. Schulman S. How I treat recurrent venous thromboembolism in patients receiving anticoagulant therapy. Blood 2017;129:3285
  5. Hull et al.  Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis. NEJM 1982;307:1676
  6. Kearon et al.  Comparison of Low-Intensity Warfarin Therapy with Conventional-Intensity Warfarin Therapy for Long-Term Prevention of Recurrent Venous Thromboembolism.  NEJM 2003;349:631
  7. Ridker et al.  Long-Term, Low-Intensity Warfarin Therapy for the Prevention of Recurrent Venous Thromboembolism.  NEJM 2003;348:1425
  8. Ost et al. Duration of Anticoagulation Following Venous Thromboembolism. A Meta-analysis.  JAMA 2005;294:706
  9. Palareti et al.  D-dimer testing to determine the duration of anticoagulation therapy. NEJM 2006;355:1780
  10. Schulman et al. A Comparison of Six Weeks with Six Months of Oral Anticoagulant Therapy after a First Episode of Venous Thromboembolism. NEJM 1995;332:1661
  11. Prandoni et al. Residual Thrombosis on Ultrasonography to Guide the Duration of Anticoagulation in Patients With Deep Venous Thrombosis. A Randomized Trial. Ann Intern Med 2009;150:577 (Prolonging duration of anticoagulation benefits patients with residual clot) (see also the accompanying editorial)
  12. Schulman et al. The Duration of Oral Anticoagulant Therapy after a Second Episode of Venous Thromboembolism. NEJM 1997;336:393
  13. Kearon et al.  A Comparison of Three Months of Anticoagulation with Extended Anticoagulation for a First Episode of Idiopathic Venous Thromboembolism. NEJM 1999;340:901
  14. Agnelli et al. Three Months versus One Year of Oral Anticoagulant Therapy for Idiopathic Deep Venous Thrombosis. NEJM 2001;345:165
  15. Agnelli et al.  Extended Oral Anticoagulant Therapy after a First Episode of Pulmonary Embolism.  Ann Intern Med 2003;139:19
  16. Couturaud et al. Six Months vs Extended Oral Anticoagulation After a First Episode of Pulmonary Embolism: The PADIS-PE Randomized Clinical Trial. JAMA 2015;314:31(24 mo vs 6 mo of anticoagulation after unprovoked PE decreased recurrence risk, increased bleeding risk, did not affect mortality. Benefit not maintained after therapy stopped)
  17. Mai et al. Extended Anticoagulation for VTE: A Systematic Review and Meta-Analysis. Chest 2019;155:1199(DOACs reduce overall mortality vs observation alone)
  18. Lee et al.  Low-Molecular-Weight Heparin versus a Coumarin for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer. NEJM 2003;349:146
  19. Becattini et al. Aspirin for preventing the recurrence of venous thromboembolism. NEJM 2012;366:1959(100 mg/day aspirin reduced recurrence rate from 11.2% to 6.6% with no increase in major bleeding; with editorial)
  20. Simes et al Aspirin for the Prevention of Recurrent Venous Thromboembolism. The INSPIRE Collaboration. Circulation 2014;130:1062(ASA reduces recurrence rate by about one-third, does not increase bleeding risk; with editorial)
  21. Lyman et al. American Society of Clinical Oncology Guideline: Recommendations for Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer. J Clin Oncol 2007;25:5490
  22. Schmidt et al. Statin use and venous thromboembolism recurrence: a combined nationwide cohort and nested case–control study. J Thromb Haemost 2014;12:1207(Statin use reduced VTE recurrence risk by about 30%; with commentary)
  23. Weitz et al. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism. NEJM 2017;376:1211 (Recurrent VTE incidence reduced by 75% with 10 mg/day rivaroxaban, major bleeding rate 0.4%/yr vs 0.3% with ASA; with editorial)
  24. Wells et al. Long-term anticoagulation with rivaroxaban for preventing recurrent VTE: A benefit–risk analysis of EINSTEIN EXTENSION. Chest 2016;150:1059 (Rivaroxaban reduced VTE incidence from 9.6% to 3% in one year; 0.7% incidence of major bleeding)
  25. Agnelli et al. Apixaban for extended treatment of venous thromboembolism. NEJM 2013;368:699 (Apixaban lowered VTE recurrence rate from 8.8% to 1.7% over 12 mo without increasing bleeding risk; with editorial)
  26. Couturaud et al. Extended treatment of venous thromboembolism with reduced-dose versus full-dose direct oral anticoagulants in patients at high risk of recurrence: a non-inferiority, multicentre, randomised, open-label, blinded endpoint trial. Lancet 2025;405:725 (Reduced dose apixaban or rivaroxaban associated with modest increase in recurrent VTE and substantial decrease in bleeding risk vs full-dose)

Postphlebitic syndrome and chronic venous insufficiency

  1. Fukaya and Kolluri. Nonsurgical Management of Chronic Venous Insufficiency. NEJM 2024;391:2350
  2. Rabinovich and Kahn. How I treat the postthrombotic syndrome. Blood 2018;131:2215
  3. Jain and Cifu. Prevention, diagnosis and treatment of postthrombotic syndrome. JAMA 2016;315:1048
  4. Baldwin et al. Post-thrombotic syndrome: a clinical review. J Thromb Haemost 2013;11:795
  5. Galanaud et al. Long‐term risk of postthrombotic syndrome after symptomatic distal deep vein thrombosis: The CACTUS‐PTS study. J Thromb Haemost 2020;18:857(24% developoed moderate or severe PTS)
  6. Singer et al. Evaluation and Management of Lower-Extremity Ulcers. NEJM 2017;377:1559
  7. Kahn et al. Determinants and Time Course of the Postthrombotic Syndrome after Acute Deep Venous Thrombosis. Ann Intern Med 2008;149:698
  8. Kahn S. How I treat postthrombotic syndrome. Blood 2009;114:4624
  9. de Araujo et al.  Managing the patient with venous ulcers.  Ann Intern Med 2003;138:326
  10. Gohel et al. A Randomized Trial of Early Endovenous Ablation in Venous Ulceration. NEJM 2018;278:2105(Ablation speeds healing)
  11. Raju and Neglén. Chronic venous insufficiency and varicose veins. NEJM 2009;360:2319
  12. Appelen et al. Compression therapy for prevention of post‐thrombotic syndrome. Cochrane Database Syst Rev 2017;9:CD004174(“Low quality evidence suggests that… stockings may reduce the occurrence of PTS after DVT”)
  13. Prandoni et al. Thigh-length versus below-knee compression elastic stockings for prevention of the postthrombotic syndrome in patients with proximal-venous thrombosis: a randomized trial. Blood 2012;119:1561(No advantage to thigh-high stockings)
  14. Kahn et al. Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial. Lancet 2014;383:880(Stockings did not prevent PTS)
  15. Cushman et al. Risk factors for peripheral venous disease resemble those for venous thrombosis: the San Diego Population Study. J Thromb Haemost 2010;8:1730
  16. Galanaud et al. Predictors of post-thrombotic syndrome in a population with a first deep vein thrombosis and no primary venous insufficiency. J Thromb Haemost 2013;11:474(Obesity and contralateral venous insufficiency increase risk of PTS)
  17. Bharath et al. Genetic polymorphisms of vein wall remodeling in chronic venous disease: a narrative and systematic review. Blood 2014;124:1242
  18. Amin et al. Reduced incidence of vein occlusion and postthrombotic syndrome after immediate compression for deep vein thrombosis. Blood 2018;132:2298
  19. Soares et al. Comparison of the recanalization rate and postthrombotic syndrome in patients with deep venous thrombosis treated with rivaroxaban or warfarin. Surgery 2019 (Epub). (Postthrombotic syndrome in 29% of warfarin treated patients vs 9% of rivaroxaban treated patients after 1 year in this small randomized trial)

VTE and oral contraceptives or hormone replacement therapy

  1. Vinogradova et al. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2019;364:k4810(Transdermal preparations did not increase VTE risk)
  2. Roach et al. The risk of venous thrombosis in women over 50 years old using oral contraception or postmenopausal hormone therapy. J Thromb Haemost 2013;11:124(OC users had 6.3 fold greater VTE risk, HRT uses had 4-fold greater risk; non-oral HRT safe)
  3. van Vlijmen et al. The impact of a male or female thrombotic family history on contraceptive counseling: a cohort study. J Thromb Haemost 2016;14:1741(FH of hormone-related VTE increases risk)
  4. van Vlijmen et al. Combined oral contraceptives, thrombophilia and the risk of venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost 2016;14:1393(FVL or prothrombin mutation alone not sufficient reason to withhold OC)
  5. Sweetland et al. Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study. J Thromb Haemost 2012;10:2277(Highest risk with estrogen-progestin combination, no increased risk with transdermal estrogen)
  6. Hugon-Rodin  et al. Longitudinal profile of estrogen-related thrombotic biomarkers after cessation of combined hormonal contraceptives. Blood 2024;143:70 (Thrombotic risk declines 2-4 weeks after stopping)
  7. Bird et al. Drospirenone and non-fatal venous thromboembolism: is there a risk difference by dosage of ethinyl-estradiol? J Thromb Haemost 2013;11:1059
  8. Holmegard et al. Endogenous sex hormones and risk of venous thromboembolism in women and men. J Thromb Haemost 2014;12:297(High endogenous estradiol or testosterone levels did not increase VTE risk)
  9. Eischer et al. The risk of recurrence in women with venous thromboembolism while using estrogens: a prospective cohort study. J Thromb Haemost 2014;12:635(Low risk of recurrence – 6% in 5 yrs – after stopping anticoagulation)
  10. Martinelli et al. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use. Blood 2016;127:1417 (Estrogen-containing hormonal therapy is safe in an anticoagulated patient)
  11. Verlaan et al. Hormonal contraceptive use after a first venous thrombotic event and the risk of recurrence in premenopausal women. J Thromb Haemost 2024;22:2150 (OCP use safe during anticoagulation treatment but VTE risk high if OCP continued after stopping AC)
  12. Li et al. Association of Risk for Venous Thromboembolism With Use of Low-Dose Extended- and Continuous-Cycle Combined Oral Contraceptives. A Safety Study Using the Sentinel Distributed Database. JAMA Intern Med 2018;178:1482 (Small increase in VTE risk with greater estrogen exposure)
  13. Scheres et al. Effect of gender-affirming hormone use on coagulation profiles in transmen and transwomen. J Thromb Haemost 2021;19:1029 (Androgens cause procoagulant changes, estrogens do not)
  14. Mullins and Mullins. Thrombotic risk associated with gender-affirming hormone therapy. J Thromb Haemost 2024;22:2129

Pregnancy

  1. Bates et al. VTE, Thrombophilia, Antithrombotic Therapy, and Pregnancy. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e691S
  2. Merz et al. Thrombotic complications in pregnancy: a case-based review of the evidence. J Thromb Haemost 2025;23:417
  3. Greer I. Pregnancy complicated by venous thrombosis. NEJM 2015;373:540
  4. Middeldorp and Ganzevoort. How I treat venous thromboembolism in pregnancy. Blood 2020;136:2133
  5. Sultan et al. Development and validation of risk prediction model for venous thromboembolism in postpartum women: multinational cohort study. BMJ 2016;355:ir253
  6. Righini et al. Diagnosis of Pulmonary Embolism During Pregnancy: A Multicenter Prospective Management Outcome Study. Ann Intern Med 2018;169:766
  7. Sultan et al. Impact of risk factors on the timing of first postpartum venous thromboembolism: a population-based cohort study from England. Blood 2014;124:2872(Preeclampsia and postpartum infection, BMI>30 or C-section associated with increased risk for 6 weeks pospartum; postpartum hemorrhage and preterm birth increased risk during 1st 3 weeks only)
  8. Romualdi et al. Anticoagulant therapy for venous thromboembolism during pregnancy: a systematic review and a meta-analysis of the literature. J Thromb Haemost 2013;11:270
  9. Heit et al. Trends in the Incidence of Venous Thromboembolism during Pregnancy or Postpartum: A 30-Year Population-Based Study. Ann Intern Med 2005;143:697
  10. Heit et al. Trends in the Incidence of Venous Thromboembolism during Pregnancy or Postpartum: A 30-Year Population-Based Study. Ann Intern Med 2005;143:697
  11. Kamel et al. Risk of a thrombotic event after the 6-week postpartum period. NEJM 2014;370:1307(11-fold increased risk of thrombosis in first 6 weeks after delivery, 2-fold increased risk in next 6 weeks)
  12. Sultan et al. Risk factors for first venous thromboembolism around pregnancy: a population-based cohort study from the United Kingdom. Blood 2013;121:3953(Stillbirth, C-section, obstetric hemorrhage, medical comorbidities and BMI > 30 strong risk factors for postpartum VTE)
  13. Olausson et al. Incidence of pulmonary and venous thromboembolism in pregnancies after in vitro fertilization with fresh respectively frozen‐thawed embryo transfer: Nationwide cohort study. J Thromb Haemost 2020;18:1965(> 8-fold higher VTE incidence than in pregnancies following natural conception)
  14. Greer and Nelson-Piercy. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood 2005;106:401
  15. Patel et al. Population Pharmacokinetics of Enoxaparin During the Antenatal Period. Circulation 2013;128:1462(Half-life of enoxaparin prolonged in later pregnancy, once-daily administration may be appropriate)
  16. Salim et al. Adjusting enoxaparin dosage according to anti-FXa levels and pregnancy outcome in thrombophilic women. A randomised controlled trial. Thromb Haemost 2016; 116:687(Adjusting dose according to anti-Xa levels did not improve outcomes)
  17. Cox et al. Effectiveness and safety of thromboprophylaxis with enoxaparin for prevention of pregnancy‐associated venous thromboembolism. J Thromb Haemost 2019;17:1160(40 mg/d of enoxaparin associated with low rate of VTE)
  18. Bistervels et al. Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial. Lancet 2022;400:1777 (Modest, non-significant reduction in VTE with intermediate dose LMWH; no difference in bleeding)
  19. Mazzolai et al. Fondaparinux is a safe alternative in case of heparin intolerance during pregnancy. Blood 2006;108:1569
  20. Bates and Ginsberg.  How we manage venous thromboembolism during pregnancy.  Blood 2002;100:3470
  21. Bistervels et al. Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial. Lancet 2022;400:1777 (Low dose LMWH as effective as weight-adjusted intermediate dose LMWH)
  22. Mantha et al. Low molecular weight heparin to achieve live birth following unexplained pregnancy loss: a systematic review. J Thromb Haemost 2010;8:263(Not enough evidence to justify routine use of LMWH in this setting)
  23. Rodger et al. Meta-analysis of low-molecular-weight heparin to prevent recurrent placenta-mediated pregnancy complications. Blood 2014;123:822(LMWH treatment reasonable in women with hx of late pregnancy loss, pre-eclampsia, placental abruption, or SGA newborn)
  24. Rodger et al. Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials. Lancet 2016;388:2629(No apparent benefit to LMWH in this setting)
  25. Kaandorp et al. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. NEJM 2010;362:1586(Neither treatment improved live-birth rate)
  26. Clark et al. SPIN: the Scottish Pregnancy Intervention Study: a multicentre randomised controlled trial of low molecular weight heparin and low dose aspirin in women with recurrent miscarriage. Blood 2010;115:4162(Antithrombotic treatment did not improve live-birth rate)
  27. Schleussner et al. Low-Molecular-Weight Heparin for Women With Unexplained Recurrent Pregnancy Loss: A Multicenter Trial With a Minimization Randomization Scheme. Ann Intern Med 2015;162:601(No improvement in live-birth rates with LMWH injections)
  28. Martinelli et al. Heparin in pregnant women with previous placenta-mediated pregnancy complications: a prospective, randomized, multicenter, controlled clinical trial. Blood 2012;119:3269(LMWH did not prevent late pregnancy complications)
  29. Pasquier et al. Enoxaparin for prevention of unexplained recurrent miscarriage: a multicenter randomized double-blind placebo-controlled trial. Blood 2015;125:2200(No apparent benefit from enoxaparin treatment)
  30. Kingdom and Drewlo. Is heparin a placental anticoagulant in high-risk pregnancies? Blood 2011;118:4780
  31. Özkan et al. Thrombolytic Therapy for the Treatment of Prosthetic Heart Valve Thrombosis in Pregnancy With Low-Dose, Slow Infusion of Tissue-Type Plasminogen Activator. Circulation 2013;128:532
  32. van Hagen et al. Pregnancy in Women With a Mechanical Heart Valve. Data of the European Society of Cardiology Registry of Pregnancy and Cardiac Disease (ROPAC). Circulation 2015;132:132(Only 58% of pregnancies were uncomplicated and resulted in a live birth; with editorial)

Venous thrombosis in unusual locations

  1. Abbattista et al. Treatment of unusual thrombotic manifestations. Blood 2020;135:326
  2. Janczak et al. Rivaroxaban and Apixaban for Initial Treatment of Acute Venous Thromboembolism of Atypical Location. Mayo Clin Proc 2018; 93:40(Efficacy and safety similar to that in patients with VTE in typical locations)
  3. Lamontagne et al. Nonleg Venous Thrombosis in Critically Ill Adults. A Nested Prospective Cohort Study. JAMA Int Med 2014;174:689
  4. Martinelli et al. How I treat rare venous thromboses. Blood 2008;112:4818

Upper extremity vein thrombosis

  1. Kucher N. Deep-vein thrombosis of the upper extremities. NEJM 2011; 364:861
  2. Bleker et al. Current management strategies and long-term clinical outcomes of upper extremity venous thrombosis. J Thromb Haemost 2016;14:973
  3. Kleinjan et al. Safety and Feasibility of a Diagnostic Algorithm Combining Clinical Probability, d-Dimer Testing, and Ultrasonography for Suspected Upper Extremity Deep Venous Thrombosis: A Prospective Management Study. Ann Intern Med 2014;160:451
  4. Sartori et al. Whole-Arm Ultrasound to Rule Out Suspected Upper-Extremity Deep Venous Thrombosis in Outpatients. JAMA Intern Med 2015;175:1226(>98% sensitivity; editorial)
  5. Lechner et al. Comparison between idiopathic deep vein thrombosis of the upper and lower extremity regarding risk factors and recurrence. J Thromb Haemost 2008; 6:1269(lower incidence of thrombophilia, PE risk, and recurrence risk with arm DVT)
  6. Muñoz et al. Clinical outcome of patients with upper-extremity deep vein thrombosis. Results from the RIETE registry. Chest 2008;133:143
  7. Flinterman et al. Recurrent Thrombosis and Survival After a First Venous Thrombosis of the Upper Extremity. Circulation 2008;118:1366

Catheter-associated thrombosis

  1. Barco et al. Home parenteral nutrition-associated thromboembolic and bleeding events: results of a cohort study of 236 individuals. J Thromb Haemost 2016;14:1364
  2. Evans et al. Risk of symptomatic DVT associated with peripherally inserted central catheters. Chest 2010;138:803(Prior DVT, larger catheter, longer surgery duration predicted DVT)
  3. Winters et al. Central venous catheters and upper extremity deep vein thrombosis in medical inpatients: the Medical Inpatients and Thrombosis (MITH) Study. J Thromb Haemost 2015;13:2155(Catheter-associated upper extremity clots account for half of hospital-acquired DVTs in medical patients; risk higher with peripherally-inserted catheters)
  4. Kizhakkedathu and Conway. Biomaterial and cellular implants: foreign surfaces where immunity and coagulation meet. Blood 2022;139:1987
  5. Guan et al. Rivaroxaban and apixaban are less effective than enoxaparin for the prevention of catheter-induced clotting in vitro. J Thromb Haemost 2023;21:76 (Not a clinical study)

Splanchnic vein thrombosis

  1. Barnum et al. Splanchnic vein thrombosis: management for the thrombosis specialist. J Thromb Haemost 2025;23:404
  1. Guerrero et al. Anticoagulation improves survival in patients with cirrhosis and portal vein thrombosis: The IMPORTAL competing-risk meta-analysis. J Hepatol 2023;79:69
  2. Carlin et al. Anticoagulation for stroke prevention in atrial fibrillation and treatment of venous thromboembolism and portal vein thrombosis in cirrhosis: guidance from the SSC of the ISTH. J Thromb Haemost 2024;22:2653
  3. Chrysafi et al. Anticoagulation for splanchnic vein thrombosis in myeloproliferative neoplasms: a systematic review and meta-analysis. J Thromb Haemost 2024;22:3479
  4. Di Nisio et al. Anticoagulant therapy for splanchnic vein thrombosis. ISTH SSC Subcommittee Control of Anticoagulation. J Thromb Haemost 2020;18:1562
  5. Valeriani et al. Anticoagulant therapy for splanchnic vein thrombosis: a systematic review and meta-analysis. Blood 2021;137:1233(“Anticoagulant therapy improves SVT recanalziation and reduces risk of thrombosis progression without increasing major bleeding”)
  6. Ageno et al. Rivaroxaban for the treatment of noncirrhotic splanchnic vein thrombosis: an interventional prospective cohort study. Blood Adv 2022;6:3569 (Supports DOAC use in this setting)
  7. Plessier et al. Rivaroxaban Prophylaxis in Noncirrhotic Portal Vein Thrombosis. NEJM Evid 2022 (Epub) (Long term DOAC treatment reduced incidence of recurrent thrombosis from 19.7/100 patient-yrs to zero, with minimal difference in bleeding events)
  8. Garcia-Pagán and Valla. Primary Budd-Chiari Syndrome. NEJM 2023;388:1307
  9. Ageno et al. Incidence rates and case fatality rates of portal vein thrombosis and Budd-Chiari Syndrome. Thromb Haemost 2017;117:794
  10. Clair et al. Mesenteric ischemia. NEJM 2016;374:959
  11. Murad et al. Etiology, management, and outcome of the Budd-Chiari syndrome. Ann Interm Med 2009;151:167(50% of patients in this series had a myeloproliferative disorder)
  12. Ageno et al. How I treat splanchnic vein thrombosis. Blood 2014;124:3685
  13. Ageno et al. Long-term Clinical Outcomes of Splanchnic Vein Thrombosis. Results of an International Registry. JAMA Intern Med 2015;175:1474(“Most patients with SVT have a substantial long-term risk of thrombotic events…anticoagulant treatment appears to be safe and effective in most patients”)
  14. Candeloro et al. Clinical course and treatment of incidentally detected splanchnic vein thrombosis: an individual patient data meta-analysis. J Thromb Haemost 2023;21:1592 (Anticoagulant therapy reduced recurrence risk, caused little bleeding)
  15. De Gottardi et al. Antithrombotic treatment with direct-acting oral anticoagulants (DOACs) in patients with splanchnic vein thrombosis and cirrhosis. Liver Int 2016 (Epub) (Retrospective analysis of 94 cases; DOACs appear effective and safe)
  16. Naymagon et al. The efficacy and safety of direct oral anticoagulants in noncirrhotic portal vein thrombosis. Blood Adv 2020;4:655
  17. Boissinot et al. Latent myeloproliferative disorder revealed by the JAK2-V617F mutation and endogenous megakaryocytic colonies in patients with splanchnic vein thrombosis. Blood 2006;108:3223
  18. De Stefano et al. Incidence of the JAK2 V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders. J Thromb Haemost 2007;5:708(22% of patients with SVT without overt MPD were JAK2-positive)
  19. Smalberg et al. Myeloproliferative neoplasms in Budd-Chiari syndrome and portal vein thrombosis: a meta-analysis. Blood 2012;120:4921(30-40% of patients with splanchnic vein thrombosis have a myeloproliferative disorder or bear the JAK2 mutation)
  20. Spaander et al. Anticoagulant therapy in patients with non-cirrhotic portal vein thrombosis: effect on new thrombotic events and gastrointestinal bleeding. J Thromb Haemost 2013;11:452(Recurrent thrombosis more common in patients with inherited or acquired prothrombotic conditions)
  21. Villa et al. Enoxaparin Prevents Portal Vein Thrombosis and Liver Decompensation in Patients With Advanced Cirrhosis. Gastroenterology 2012;143:1263(Lower incidences of PVT, liver decompensation & death in enoxaparin-treated pts; no bleeding events)
  22. Hoekstra et al. Long-term follow-up of patients with portal vein thrombosis and myeloproliferative neoplasms. J Thromb Haemost 2011;9:2208(Recurrent or progressive thrombosis in up to 50%; mortality mainly due to underlying disease rather than thrombosis)
  23. Riva et al. Safety of vitamin K antagonist treatment for splanchnic vein thrombosis: a multicenter cohort study. J Thromb Haemost 2015;13:1019(Major bleeding rate 1.24/100 pt-yrs in this cohort of selected patients, similar to rates reported for other VTE patients; presence of varices an independent predictor of bleeding)
  24. Riva et al. Clinical history and antithrombotic treatment of incidentally detected splanchnic vein thrombosis: a multicentre, international prospective registry. Lancet Haematol 2016;3:e267(Prognosis similar to that of clinically suspected SVT, antithrombotic therapy appeared beneficial; most patients had cirrhosis or cancer)
  25. Duceppe et al. Incidence and predictors of splanchnic vein thrombosis and mortality following hepatobiliary and pancreatic surgery. J Thromb Haemost 2021;19:797(Incidence about 1/30, associated with 3-fold higher mortatlity within 90 days)
  26. Shang et al. Natural history of cancer-associated splanchnic vein thrombosis. J Thromb Haemost 2024;22:1421

Cerebral venous thrombosis

  1. Dix and Hunt. The changing face of cerebral venous sinus thrombosis—emerging new causes and treatments. J Thromb Haemost 2024;22:3346
  2. Ropper and Klein. Cerebral venous thrombosis. NEJM 2021;385:59
  3. Capecchi et al. Cerebral venous sinus thrombosis. J Thromb Haemost 2018;16:1918
  4. Dentali et al. Natural history of cerebral vein thrombosis: a systematic review.  Blood 2006;108:1129
  5. Stam J. Thrombosis if the cerebral veins and sinuses.  NEJM 2005;352:1791
  6. Martinelli et al. Long-term evaluation of the risk of recurrence after cerebral sinus-venous thrombosis. Circulation 2010;121:2740(3% had recurrent CST and 7% had DVT or PE; most recurrences in first year after stopping treatment)
  7. Pires et al. Risk factors associated with recurrent venous thromboembolism after a first cerebral venous thrombosis event: A cohort study. Thromb Res 2019;178:85 (6.9% recurrence rate within 3 yrs; men and FVL carriers had higher risk)
  8. Ferro et al. Safety and Efficacy of Dabigatran Etexilate vs Dose-Adjusted Warfarin in Patients With Cerebral Venous Thrombosis: A Randomized Clinical Trial. JAMA Neurol 2019 (Epub)
  9. Bose et al. Direct oral anticoagulants in treatment of cerebral venous thrombosis: a systematic review. BMJ Open 2021;11:e040212(New ICH in 0.7%, recurrent CVT in 1.5% of DOAC-treated patients)

Retinal vein thrombosis

  1. Scott et al. Retinal vascular occlusions. Lancet 2020;396:1927
  2. Wong and Scott. Retinal-vein occlusion. NEJM 2010;363:2135
  3. Valeriani et al. Antithrombotic treatment for retinal vein occlusion: a systematic review and meta-analysis. J Thromb Haemost 2023;21:284 (Better outcomes with anticoagulation than antiplatelet therapy)
  4. Romiti et al. Inherited and acquired thrombophilia in adults with retinal vascular occlusion: A systematic review and meta‐analysis. J Thromb Haemost 2020;18:3249 (No increase in prevalence of inherited thrombophilia in RVO patients vs healthy controls)

Ovarian vein/ and other GU sites

  1. Monnet et al. Epidemiology, natural history, diagnosis, and management of ovarian vein thrombosis: a scoping review. J Thromb Haemost 2024;2991
  2. Sterlicchi and Henry. Ovarian vein thrombus: is treatment necessary? Blood 2016;128:1433 (abstract) (Incidentally discovered OVT may not require anticoagulation)
  3. Amin et al. The prevalence of incidental uterine venous plexus thrombosis in women attending a gynecology clinic. J Thromb Haemost 2020;18:2557
  4. Wouterlood et al. Pregnancy-associated pelvic vein thrombosis: Insights from a multicenter case series. J Thromb Haemost 2021;19:1926

Superficial venous thrombosis

  1. Piazza et al. Superficial Vein Thrombosis: A Review. JAMA 2025 (Epub)
  2. Cosmi B. Management of superficial venous thrombosis. J Thromb Haemost 2015;13:1175
  3. Kitchens CS. How I treat superficial venous thrombosis. Blood 2011;117:39
  4. Decousus et al. Superficial Venous Thrombosis and Venous Thromboembolism. A Large, Prospective Epidemiologic Study. Ann Intern Med 2010;152:218(25% of patients had DVT or PE at diagnosis; another 10% had VTE within 3 months)
  5. Galanaud et al. Long-term risk of venous thromboembolism recurrence after isolated superficial vein thrombosis. J Thromb Haemost 2017;15:1123(Recurrence rate about 5% per year, most recurrences as superficial clots)
  6. Barco et al. Clinical course of patients with symptomatic isolated superficial vein thrombosis: the ICARO follow-up study. J Thromb Haemost 2017;15:2176(Men and cancer patients at higher risk for DVT/PE; negligible risk of death in patients without cancer)
  7. Decousus et al. Fondaparinux for the Treatment of Superficial-Vein Thrombosis in the Legs. NEJM 2010;363:1222(Plus editorial)
  8. Beyer-Westendorf et al. Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, non-inferiority SURPRISE phase 3b trial. Lancet Haematol 2017; 4:e105(Rivaroxaban 10 mg/d as effective and safe as fondaparinux 2.5 mg/d)
  9. Leizorovicz et al. Clinical relevance of symptomatic superficial-vein thrombosis extension: lessons from the CALISTO study. Blood 2013;122:1724 (Symptomatic extension of SVT occured in 7.3% of placebo-treated patients in above study; about 9% of patients with extension developed DVT or PE)
  10. van Langevelde et al. Increased risk of venous thrombosis in persons with clinically diagnosed superficial vein thrombosis: results from the MEGA study. Blood 2011;118:4239(6-fold increased risk of DVT, 4-fold increased risk of PE)
  11. Roach et al. The risk of venous thrombosis in individuals with a history of superficial vein thrombosis and acquired venous thrombotic risk factors. Blood 2013;122:4264(Surgery, cast immobilization, pregnancy, or cancer + hx SVT = 30x higher DVT risk)
  12. Cannegieter et al. Risk of venous and arterial thrombotic events in patients diagnosed with superficial vein thrombosis: a nationwide cohort study. Blood 2015;125:229(3.4% incidence of DVT or PE within 3 mo of isolated SVT; risk remains high for over 5 y)
  13. Di Minno et al. Prevalence of deep vein thrombosis and pulmonary embolism in patients with superficial vein thrombosis: a systematic review and meta-analysis. J Thromb Haemost 2016;14:964 (DVT and PE prevalence in patients with SVT about 18% and 7% respectively)
  14. Frappé et al. Annual diagnosis rate of superficial vein thrombosis of the lower limbs: the STEPH community-based study. J Thromb Haemost 2014;12:831(Incidence 0.64%/yr; 25% had concomitant DVT, 5% had PE)

Chronic thromboembolic pulmonary hypertension

  1. Fauché et al. Frequency and predictors for chronic thromboembolic pulmonary hypertension after a first unprovoked pulmonary embolism: Results from PADIS studies. J Thromb Haemost 2022;20:2850 (Incidence 1-2%; predictors include degree of pulm. vascular obstruction at diagnosis & at 6 mo, age >65, APL antibodies and non-O blood type)
  2. Klok et al. Chronic thromboembolic pulmonary hypertension from the perspective of patients with pulmonary embolism. J Thromb Haemost 2018;16:1040
  3. Piazza and Goldhaber. Chronic thromboembolic pulmonary hypertension. NEJM 2011;364:351
  4. Pengo et al. Incidence of Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Embolism.  NEJM 2004;350:2257
  5. Condliffe et al. Improved Outcomes in Medically and Surgically Treated Chronic Thromboembolic Pulmonary Hypertension. Am J Respir Crit Care Med 2008; 177:1122
  6. Pepke-Zaba et al. Chronic thromboembolic pulmonary hypertension (CTEPH). Results from an international prospective registry. Circulation 2011;124:1973
  7. Delcroix et al. Long-Term Outcome of Patients With Chronic Thromboembolic Pulmonary Hypertension. Results From an International Prospective Registry. Circulation 2016;133:859(3-year survival nearly 90% in both operated and non-operated patients)
  8. Guérin et al. Prevalence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Prevalence of CTEPH after pulmonary embolism. Thromb Haemost 2014;112:598(Higher incidence than previously thought; presentation can mimic acute PE)
  9. Suntharalingam et al. Long-term Use of Sildenafil in Inoperable Chronic Thromboembolic Pulmonary Hypertension. Chest 2008;134:229
  10. Bunclark et al. A multicenter study of anticoagulation in operable chronic thromboembolic pulmonary hypertension. J Thromb Haemost 2020;18:114 (Retrospective analysis suggesting higher rates of recurrent VTE with DOACs vs VKA)
  11. Hosokawa et al. Long-term outcome of chronic thromboembolic pulmonary hypertension using direct oral anticoagulants and warfarin: a Japanese prospective cohort study. J Thromb Haemost 2023;21:2151 (DOACS as efficacious as warfarin, safer)
  12. Gerges et al. Microvascular Disease in Chronic Thromboembolic Pulmonary Hypertension. Hemodynamic Phenotyping and Histomorphometric Assessment. Circulation 2020;141:376 (Small vessel disease detected by pulmonary artery occlusion waveform analysis predicts worse outcomes after pulmonary endarterectomy)
  13. Klok et al. Incidence and clinical course of chronic thromboembolic pulmonary hypertension with or without a history of venous thromboembolism in Denmark. J Thromb Haemost 2024;22:3562  (Higher incidence of VTE in patients with history of same, and better survival)

Vena cava filters/venous stents

  1. Duffett and Carrier. Inferior vena cava filters. J Thromb Haemost 2017;15:3
  2. White et al. High Variation Between Hospitals in Vena Cava Filter Use for Venous Thromboembolism. JAMA Intern Med 2013;173:506
  3. Saeed et al. Trends in Inferior Vena Cava Filter Placement by Indication in the United States From 2005 to 2014. JAMA Intern Med 2017;177:1861 (IVC filter placement rate increased from 2005 to 2010, decreased thereafter)
  4. Warren et al. Trends in FDA Adverse Events Reporting for Inferior Vena Cava Filters and Estimated Insertions in the US, 2016 to 2020. JAMA Intern Med 2023;183:271
  5. Decousus et al. A Clinical Trial of Vena Caval Filters in the Prevention of Pulmonary Embolism in Patients with Proximal Deep-Vein Thrombosis. NEJM 1998;338:409
  6. The PREPIC Study Group. Eight-Year Follow-Up of Patients With Permanent Vena Cava Filters in the Prevention of Pulmonary Embolism. The PREPIC (Prévention du Risque d�Embolie Pulmonaire par Interruption Cave) Randomized Study. Circulation 2005;112:416(8 year followup of above trial; filters decreased PE risk, increased DVT risk, and did not affect survival)
  7. Mismetti et al. Effect of a Retrievable Inferior Vena Cava Filter Plus Anticoagulation vs Anticoagulation Alone on Risk of Recurrent Pulmonary Embolism: A Randomized Clinical Trial. JAMA 2015;313:1627(More recurrent PE in filter group than in control group)
  8. White et al. Outcomes After Vena Cava Filter Use in Noncancer Patients With Acute Venous Thromboembolism. A Population-Based Study. Circulation 2016;133:2018(Filters reduced mortality in patients with acute VTE and contraindication to anticoagulation, not in other patients; they markedly increased risk of subsequent DVT. With editorial)
  9. Spencer et al. A Population-Based Study of Inferior Vena Cava Filters in Patients With Acute Venous Thromboembolism. Arch Intern Med 2010;170:1456(13% of patients had IVC filters placed after acute VTE. Filters used inappropriately in at least 26% of cases)
  10. Ho et al. A Multicenter Trial of Vena Cava Filters in Severely Injured Patients. NEJM 2019;381:328(Filters did not reduce incidence of PE or death)
  11. Sarosiek et al. Indications, Complications, and Management of Inferior Vena Cava FiltersThe Experience in 952 Patients at an Academic Hospital With a Level I Trauma Center. JAMA Intern Med 2013;173:513(Only 8.5% of “removable” filters removed; 7.8% incidence of VTE with filter in place. With editorial)
  12. Hajduk et al. Vena Cava Filter Occlusion and Venous Thromboembolism Risk in Persistently Anticoagulated Patients. A Prospective, Observational Cohort Study.Chest 2010;137:877
  13. Streiff M.  Vena caval filters: a comprehensive review.  Blood 2000;95:3669
  14. Nicholson et al. Prevalence of Fracture and Fragment Embolization of Bard Retrievable Vena Cava Filters and Clinical Implications Including Cardiac Perforation and Tamponade. Arch Intern Med 2010;170:1827(16% incidence of strut fracture, some with life-threatening consequences)
  15. Desai et al. Retrieval of Inferior Vena Cava Filters With Prolonged Dwell Time. A Single-Center Experience in 648 Retrieval Procedures. JAMA Intern Med 2015;175:1572(Removing retrievable filters safe regardless of dwell time)
  16. Rajasekhar and Crowther. ASH evidence-based guidelines: what is the role of inferior vena cava filters in the perioperative prevention of venous thromboembolism in bariatric surgery patients? Hematology 2009;302
  17. Jia et al. Caval Penetration by Inferior Vena Cava Filters. A Systematic Literature Review of Clinical Significance and Management. Circulation 2015;132:944(19% incidence; most patients asymptomatic but about 1/5 had organ or structural damage)
  18. Notten et al Postinterventional antithrombotic management after venous stenting of the iliofemoral tract in acute and chronic thrombosis: A systematic review. J Thromb Haemost 2021;19:753(“The impact of postinterventional antithrombotic therapy on stent patency remains unknown because of limited and insufficient data”)
  19. Barco et al. Aspirin Plus Rivaroxaban Versus Rivaroxaban Alone for the Prevention of Venous Stent Thrombosis Among Patients With Post-Thrombotic Syndrome: The Multicenter, Multinational, Randomized, Open-label ARIVA Trial. Circulation 2025 (Epub) (ASA + rivaroxaban gave patency rates similar to rivaroxaban alone; both > 90% at 6 mo)

Arterial disease

Arterial thrombosis: general

  1. Vandvik et al. Primary and Secondary Prevention of Cardiovascular Disease. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e637S
  2. Swan et al. Dilemmas in hematology: consults in patients with arterial thrombosis. J Thromb Haemost 2023;21:421 (Discusses LV thrombus, stroke with PFO, thrombophilia testing)
  3. Davi et al. Platelet activation and atherothrombosis. NEJM 2007;357:2482
  4. Swan et al. Dilemmas in hematology: consults in patients with arterial thrombosis. J Thromb Haemost 2023;21:421
  5. May and Moll. How I treat unexplained arterial thrombosis. Blood 2020;136:1487
  6. Lidegaard et al. Thrombotic stroke and myocardial infarction with hormonal contraception. NEJM 2012;366:2257(Relative risk of arterial events increased with increasing dose of ethinyl estradiol)
  7. Vidula et al. Biomarkers of Inflammation and Thrombosis as Predictors of Near-Term Mortality in Patients with Peripheral Arterial Disease: A Cohort Study. Ann Intern Med 2008;148:85
  8. Green D. Risk of future arterial cardiovascular events in patients with idiopathic venous thromboembolism. Hematology 2009;259
  9. Fries and Grosser. The Cardiovascular Pharmacology of COX-2 Inhibition. Hematology 2005:445-451
  10. Ridker et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. NEJM 2005;352:1293  (aspirin lowered risk of stroke, but not risk of MI or cardiovascular death, in healthy women over 45 years)
  11. Dentali et al. Combined Aspirin and Oral Anticoagulant Therapy Compared With Oral Anticoagulant Therapy Alone Among Patients at Risk for Cardiovascular Disease. A Meta-analysis of Randomized Trials. Arch Intern Med 2007;167:117
  12. The Warfarin Antiplatelet Vascular Evaluation Trial Investigators. Oral Anticoagulant and Antiplatelet Therapy and Peripheral Arterial Disease. NEJM 2007;357:217(Adding warfarin to antiplatelet therapy did not increase efficacy but did increase bleeding risk. See also the accompanying editorial)
  13. Patrono et al. Low-dose aspirin for the prevention of atherothrombosis. NEJM 2005;353:2373
  14. Antithrombotic Trialists’ Collaboration.  Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71
  15. Bhatt et al. Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events. NEJM 2006;354:1706  (Addition of clopidogrel to aspirin not significantly more effective than aspirin alone in reducing rate of MI, stroke, or death from cardiovascular disease)

Acute coronary syndromes/myocardial infarction

  1. Rodriguez and Harrington. Management of Antithrombotic Therapy after Acute Coronary Syndromes. NEJM 2021;384:452
  2. Anand et al. Relationship of Activated Partial Thromboplastin Time to Coronary Events and Bleeding in Patients With Acute Coronary Syndromes Who Receive Heparin. Circulation. 2003;107:2884
  3. FUTURA/OASIS-8 Trial Group. Low-Dose vs Standard-Dose Unfractionated Heparin for Percutaneous Coronary Intervention in Acute Coronary Syndromes Treated With Fondaparinux. JAMA 2010;304:1339(Higher rates of death, MI and vessel occlusion, no less major bleeding with low-dose heparin)
  4. Erlinge et al. Bivalirudin versus Heparin Monotherapy in Myocardial Infarction. NEJM 2017;377:1132(No apparent advantage to using bivalirudin in patients undergoing PCI for MI)
  5. Li et al. Bivalirudin plus a high-dose infusion versus heparin monotherapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomised trial. Lancet 2022;400:1847 (Better outcomes with bivalirudin)
  6. LaPointe et al. Enoxaparin Dosing and Associated Risk of In-Hospital Bleeding and Death in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes. Arch Intern Med 2007;167:1539
  7. Fox et al. Influence of Renal Function on the Efficacy and Safety of Fondaparinux Relative to Enoxaparin in Non–ST-Segment Elevation Acute Coronary Syndromes. Ann Intern Med 2007;147:304(Fondaparinux safer in patients with impaired renal function)
  8. Blasco-Colmenares et al. Aspirin Plus Clopidogrel and Risk of Infection After Coronary Artery Bypass Surgery. Arch Intern Med 2009;169: 788(50% increased incidence of infection associated with dual antiplatelet therapy, vs aspirin alone)
  9. Resor et al. Impact of Optimal Medical Therapy in the Dual Antiplatelet Therapy Study. Circulation 2016;134:989(Extending dual antiplatelet therapy beyond 1 yr post stenting reduced cardiovascular events regardless of other therapies, but increased bleed risk)
  10. Andersson et al. Association of Clopidogrel Treatment With Risk of Mortality and Cardiovascular Events Following Myocardial Infarction in Patients With and Without Diabetes. JAMA 2012;308:882(Less benefit from clopidogrel in diabetics)
  11. Wiviott et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. NEJM 2007;357:2001(Prasugrel treatment associated with fewer ischemic events but more bleeding)
  12. Morrow et al. Effect of the Novel Thienopyridine Prasugrel Compared With Clopidogrel on Spontaneous and Procedural Myocardial Infarction in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38. Circulation 2009;119:2758(24% reduction in MI risk with prasugrel)
  13. Wallentin et al. Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes. NEJM 2009;361:1045(see also the accompanying editorial)
  14. You et al. Association of Ticagrelor vs Clopidogrel With Net Adverse Clinical Events in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention. JAMA 2020;324:1640(No difference in coronary events, more toxicity with ticagrelor in this retrospective study)
  15. Bhatt et al. Effect of Platelet Inhibition with Cangrelor during PCI on Ischemic Events. NEJM 2013;368:1303(Cangrelor + ASA arm had fewer ischemic events than clopidogrel + ASA arm, no increased bleeding; with editorial)
  16. Stone et al. Antithrombotic Strategies in Patients With Acute Coronary Syndromes Undergoing Early Invasive Management. JAMA 2007;298:2497(no benefit from adding IIb-IIIa inhibitors to bilvalirudin in angioplasty patients)
  17. Valgimigli et al. Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk. NEJM 2021;385:1643(One month of DAPT as effective as 3 months, with less bleeding)
  18. Dumaine et al. Intravenous Low-Molecular-Weight Heparins Compared With Unfractionated Heparin in Percutaneous Coronary Intervention. Quantitative Review of Randomized Trials. Arch Intern Med 2007;167:2423(LMWH heparin as effective as UH, causes less bleeding)
  19. Fox et al. Influence of Renal Function on the Efficacy and Safety of Fondaparinux Relative to Enoxaparin in Non–ST-Segment Elevation Acute Coronary Syndromes. Ann Intern Med 2007;147:304(Fondaparinux safer in patients with impaired renal function)
  20. Szummer et al. Association Between the Use of Fondaparinux vs Low-Molecular-Weight Heparin and Clinical Outcomes in Patients With Non–ST-Segment Elevation Myocardial Infarction. JAMA 2015;313:707(Fondaparinux treatment associated with less bleeding and lower mortality)
  21. Alexander et al. Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome. NEJM 2011;365:699(Apixaban increased bleeding, did not reduce ischemic events significantly)
  22. Mega et al. Rivaroxaban in patients with a recent acute coronary syndrome. NEJM 2012;366:9(Rivaroxaban reduced risk of death from cardiovascular events, with some increased risk of major bleeding)
  23. Eikelboom et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. NEJM 2017;377:1319(Rivaroxaban 2.5 mg bid +ASA had better cardiac outcomes but more bleeding than ASA alone; with editorial)
  24. Gibson et al. Recurrent Hospitalization Among Patients With Atrial Fibrillation Undergoing Intracoronary Stenting Treated With 2 Treatment Strategies of Rivaroxaban or a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy. Circulation 2017;135:323(Rivaroxaban 15 mg/d plus thienopyridine, or rivaroxaban 2.5 mg bid plus dual antiplatelet therapy, superior to VKA plus dual antiplatelet therapy)
  25. Lopes et al. Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. NEJM 2019;380:1509 (Apixaban + P2Y12 inhibitor superior to VKA + P2Y12 inhibitor; no clear benefit from addidntgASA. With editorial )
  26. Dewilde et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013;381:1107(Double therapy associated with less bleeding, no increase in thrombotic events vs triple therapy)
  27. Yeh et al. Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention. JAMA 2016;315:1735
  28. Steg et al. Anticoagulation With Otamixaban and Ischemic Events in Non–ST-Segment Elevation Acute Coronary Syndromes. The TAO Randomized Clinical Trial. JAMA 2013;310:1145(No reduction in ischemic events vs heparin, more bleeding with this intravenous Xa inhibitor)

Stroke/embolism in heart disease (AF, CHF)

  1. Joglar et al. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2023 (Epub)
  2. Hankey G. Antithrombotic Therapy for Stroke Prevention. What’s New? Circulation 2019;139:1131
  3. Lip et al. Antithrombotic Therapy for Atrial Fibrillation. CHEST Guideline and Expert Panel Report. Chest 2018;154:1121
  4. Whitlock et al. Antithrombotic and Thrombolytic Therapy for Valvular Disease. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e576S
  5. Lip and Lane. Stroke prevention in atrial fibrillation: a systematic review. JAMA 2015;313:1950
  6. Steinberg BA..How I use anticoagulation in atrial fibrillation. Blood 2016;128:2891
  7. Cools et al. Risks associated with discontinuation of oral anticoagulation in newly diagnosed patients with atrial fibrillation: Results from the GARFIELD-AF Registry. J Thromb Haemost 2021;19:2322(Stopping therapy for 7 days or more increased mortality, stroke and MI risk significantly)
  8. Hernandez et al. Comparison of the Effectiveness and Safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in Newly Diagnosed Atrial Fibrillation. Am J Cardiol 2017;(epub)(Apixaban had most favorable safety/efficacy profile)
  9. Kuno et al. Meta-analysis of Antithrombotic Therapy in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention. Am J Cardiol 2019 (Epub)(Apixaban + P2Y12 inhibitor safest)
  10. Mazurek et al. Guideline-Adherent Antithrombotic Treatment Improves Outcomes in Patients With Atrial Fibrillation: Insights From the Community-Based Darlington Atrial Fibrillation Registry. Mayo Clin Proc 2017;92:1203(Over- and undertreatment both increased risk of stroke; undertrreatment increased mortality rate)
  11. Healey et al. Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation. NEJM 2024;390:107 (ARTESIA trial. 0.78%/pt-year stroke rate with apixaban vs 1.21% with ASA. Higher nonfatal bleeding risk with apixaban; with editorial)
  12. Lip et al. Refining Clinical Risk Stratification for Predicting Stroke and Thromboembolism in Atrial Fibrillation Using a Novel Risk Factor-Based Approach. The Euro Heart Survey on Atrial Fibrillation. Chest 2010;137:263(CHADS2-VASc score)
  13. Focks et al. Low performance of bleeding risk models in the very elderly with atrial fibrillation using vitamin K antagonists. J Thromb Haemost 2016;14:1715
  14. Melgaard et al. Assessment of the CHA2DS2-VASc Score in Predicting Ischemic Stroke, Thromboembolism, and Death in Patients With Heart Failure With and Without Atrial Fibrillation. JAMA 2015;314:1030(Higher score → higher risk, but predictive accuracy “modest”)
  15. Berg et al. Performance of the ABC Scores for Assessing the Risk of Stroke or Systemic Embolism and Bleeding in Patients with Atrial Fibrillation in ENGAGE AF-TIMI 48. Circulation 2018 (Epub)(These tools outperformed CHA2DS2-VASc and HAS-BLED scores)
  16. Bekwelem et al. Extracranial Systemic Embolic Events in Patients With Nonvalvular Atrial Fibrillation. Incidence, Risk Factors, and Outcomes. Circulation 2015;132:796(0.24 events/100 patient-years or 11% of thromboembolic events in AF; 25% mortality; with editorial)
  17. McAlister elt al. The prediction of postoperative stroke or death in patients with preoperative atrial fibrillation undergoing non-cardiac surgery: a VISION sub-study. J Thromb Haemost 2015;13:1768
  18. Westenbrink et al. Anemia predicts thromboembolic events, bleeding complications and mortality in patients with atrial fibrillation: insights from the RE-LY trial. J Thromb Haemost 2015;13:699
  19. Marijon et al. Causes of Death and Influencing Factors in Patients with Atrial Fibrillation: A Competing Risk Analysis from the Randomized Evaluation of Long-Term Anticoagulant Therapy Study. Circulation 2013 (Epub)(Most deaths in anticoagulated patients not due to stroke)
  20. Gómez-Outes et al. Causes of death in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol 2016;23:2508(Most deaths due to cardiac problems, with a small fraction of deaths due to stroke and bleeding; with editorial)
  21. Xian et al. Association of Preceding Antithrombotic Treatment With Acute Ischemic Stroke Severity and In-Hospital Outcomes Among Patients With Atrial Fibrillation. JAMA 2017;317: 1057(84% of stroke patients with AF were inadequately anticoagulated; inadequately treated patients had more severe strokes and higher mortality)
  22. Torn et al. Optimal Level of Oral Anticoagulant Therapy for the Prevention of Arterial Thrombosis in Patients With Mechanical Heart Valve Prostheses, Atrial Fibrillation, or Myocardial Infarction. A Prospective Study of 4202 Patients. Arch Intern Med 2009;169:1203(Optimal range 2.5-2.9 for prosthetic valves, 3.0-3.4 for AF, 3.5-3.9 for MI)
  23. Adam et al. Comparative Effectiveness of Warfarin and New Oral Anticoagulants for the Management of Atrial Fibrillation and Venous Thromboembolism: A Systematic Review. Ann Intern Med 2012;157:796
  24. Reynolds et al. Warfarin Anticoagulation and Outcomes in Patients With Atrial Fibrillation. Chest 2004126:1938(Supports target INR range of 2-3)
  25. Singer et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 2009;151:297(Patients over 85 and patients with a history of ischemic stroke benefit most; see also the accompanying editorial)
  26. Friberg et al. Net clinical benefit of warfarin in patients with atrial fibrillation. Circulation 2012;125:2298(Risk of ischemic stroke without treatment exceeds risk of intracranial bleeding with treatment in almost all patients)
  27. Agarwal et al. Current Trial-Associated Outcomes With Warfarin in Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation: A Meta-analysis. Arch Intern Med 2012;172:623(Annual incidence of stroke or embolism in warfarin-treated patients about 1.7%)
  28. Chao et al. Use of Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation Who Have a History of Intracranial Hemorrhage. Circulation 2016;133:1540(Warfarin may benefit those with CHA2DS2-VASc score ≧6)
  29. Carrero et al. Warfarin, Kidney Dysfunction, and Outcomes Following Acute Myocardial Infarction in Patients With Atrial Fibrillation. JAMA 2014;311:991(Benefits of warfarin not reduced in the presence of CKD)
  30. Shah et al. Warfarin Use and the Risk for Stroke and Bleeding in Patients With Atrial Fibrillation Undergoing Dialysis. Circulation 2014;129:1196(Warfarin did not reduce stroke risk but did increase bleeding risk in dialysis pts with Afib)
  31. ACTIVE Investigators. Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation. NEJM 2009;360:2066 (fewer strokes, more bleeding)
  32. Connolly et al. Net Clinical Benefit of Adding Clopidogrel to Aspirin Therapy in Patients With Atrial Fibrillation for Whom Vitamin K Antagonists Are Unsuitable. Ann Intern Med 2011;155:579(Post-hoc analysis of the ACTIVE trial. “Modest” net clinical benefit from adding clopidogrel)
  33. Hart et al. Meta-analysis: Antithrombotic Therapy to Prevent Stroke in Patients Who Have Nonvalvular Atrial Fibrillation. Ann Intern Med 2007;146:857 (Warfarin reduces stroke risk by 60%, ASA by 20%)
  34. Olesen et al Stroke and bleeding in atrial fibrillation with chronic kidney disease. NEJM 2012;367:625 (Increased risk of stroke or embolism in CKD; warfarin decreased risk, ASA did not; both drugs increased bleeding risk)
  35. Connolly et al. Benefit of Oral Anticoagulant Over Antiplatelet Therapy in Atrial Fibrillation Depends on the Quality of International Normalized Ratio Control Achieved by Centers and Countries as Measured by Time in Therapeutic Range. Circulation 2008;118:2029
  36. Steinberg et al. Use and Associated Risks of Concomitant Aspirin Therapy With Oral Anticoagulation in Patients With Atrial Fibrillation. Insights From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry. Circulation 2013;128:721 (Adding ASA to warfarin increases major bleeding risk by 50%)
  37. Hansen et al. Risk of Bleeding With Single, Dual, or Triple Therapy With Warfarin, Aspirin, and Clopidogrel in Patients With Atrial Fibrillation. Arch Intern Med 2010;170:1433
  38. Lamberts et al. Relation of Nonsteroidal Anti-inflammatory Drugs to Serious Bleeding and Thromboembolism Risk in Patients With Atrial Fibrillation Receiving Antithrombotic Therapy: A Nationwide Cohort Study. Ann Intern Med 2014;161:690(Higher risk of bleeding and thromboembolism with NSAID use)
  39. Connolly et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. NEJM 2009;361:1139(Dabigatran as efficacious as warfarin, caused less bleeding. See also the accompanying editorial)
  40. Calkins et al. Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation. NEJM 2017;376:1627(Less bleeding with dabigatran)
  41. Connolly et al. Apaxaban in patients with atrial fibrillation. NEJM 2011;364:806 (Apixaban better than aspirin in patients for whom warfarin treatment deemed “unsuitable”)
  42. Gibson et al. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. NEJM 2016;375:2423 (Low dose rivaroxaban plus antiplatelet therapy caused less bleeding than warfarin plus antiplatelet therapy)
  43. Yasuda et al. Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease. NEJM 2019;381:1103 (Rivaroxaban 10-15 mg/d as effective as R + antiplatelet drug, caused less bleeding; with editorial)
  44. Cho et al. Edoxaban Antithrombotic Therapy for Atrial Fibrillation and Stable Coronary Artery Disease. NEJM 2024;391:2075 (Edoxaban alone superior to edoxaban + antiplatelet therapy)
  45. Oldgren et al. Risks for Stroke, Bleeding, and Death in Patients With Atrial Fibrillation Receiving Dabigatran or Warfarin in Relation to the CHADS2 Score: A Subgroup Analysis of the RE-LY Trial. Ann Intern Med 2011;115:660(Higher CHADS2 score→ more complications)
  46. Graham et al. Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation. JAMA Int Med 2016;176:1662(Relatively high risk of intra- and extracranial bleeding with rivaroxaban)
  47. Paciaroni et al. Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non–Vitamin‐K Oral Anticoagulants (RAF‐NOACs) Study. J Am Heart Assoc 2017;6:e007034(Starting DOACs within 2 weeks of stroke associated with combined 5% rate of recurrent stroke or severe bleeding)
  48. Cannon et al. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. NEJM 2017;377:1513(Less bleeding, similar stroke risk with dabigatran plus P2Y12 inhibitor, vs warfarin plus dual antiplatelet Rx)
  49. Tannu et al. Antithrombotic Therapy to Minimize Total Events After ACS or PCI in Atrial Fibrillation: Insights From AUGUSTUS. J Am Coll Cardiol 2025 (Epub) (Apixaban safer than VKA; clopidogrel safer than ticagrelor or prasugrel; ASA increased bleeding risk)
  50. Oral et al. Risk of Thromboembolic Events After Percutaneous Left Atrial Radiofrequency Ablation of Atrial Fibrillation. Circulation 2006;114:759(1% risk of thromboembolism, usually within 2 weeks of procedure)
  51. Homma et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. NEJM 2012; 366:1859(Warfarin reduced risk of ischemic stroke vs aspirin but increased bleeding risk)
  52. Massie et al. Randomized Trial of Warfarin, Aspirin, and Clopidogrel in Patients With Chronic Heart Failure. The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) Trial. Circulation 2009;119:1616(No advantage to either warfarin or clopidogrel vs ASA)
  53. Delewi et al. Left ventricular thrombus formation after acute myocardial infarction. Heart 2012;98:1743
  54. Lee et al. Anticoagulation in ischemic left ventricular aneurysm. Mayo Clin Proc 2015;90:441(Anticoagulation may not protect against embolism in this setting)
  55. Sherwood et al. Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from ROCKET AF. Circulation 2014 (ePub).(Risk of stroke less than 0.5% per 30 days with either drug)
  56. Mas et al. Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke. NEJM 2017;377:1011(Recurrent stroke risk reduced by PFO closure)
  57. Mi et al. PFO Closure for Cryptogenic Stroke. NEJM 2018;131:1639 (Discusses the pros and cons of this procedure)
  58. Saver et al. Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke. NEJM 2017;377:1022(PFO closure reduced stroke recurrence vs medical therapy)
  59. Søndergaard et al. Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke. NEJM 2017;377:1033(PFO closure + antiplatelet therapy superior to antiplatelet therapy alone)
  60. Friedman et al. Association Between Left Atrial Appendage Occlusion and Readmission for Thromboembolism Among Patients With Atrial Fibrillation Undergoing Concomitant Cardiac Surgery. JAMA 2018;319:365(LAAO associated with lower risk of subsequent thromboembolism in this retrospective study)
  61. Chew et al. Left Atrial Appendage Occlusion Versus Oral Anticoagulation in Atrial Fibrillation. A Decision Analysis. Ann Intern Med 2022;175:1230
  62. Kirchhof et al. Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes. NEJM 2023;389:1167 (Patients with brief Afib-like events detected by monitors do not benefit from anticoagulation. With editorial)
  63. Hsieh et al. Comparing Efficacy and Safety Between Patients With Atrial Fibrillation Taking Direct Oral Anticoagulants or Warfarin After Direct Oral Anticoagulant Failure. J Am Heart Assoc 2023 (Epub) (Continuing DOAC better than switching to VKA)

Cardiac surgery/Prosthetic valves

  1. Baumann Kreuziger et al. Antithrombotic therapy management of adult and pediatric cardiac surgery patients. J Thromb Haemost 2018;16:2133
  2. Eikelboom et al. Dabigatran versus warfarin in patients with mechanical heart valves. NEJM 2013;369:1206(Dabigatran treatment associated with more thrombosis and more bleeding; see also letters to the editor)
  3. Wang et al. Apixaban or Warfarin in Patients with an On-X Mechanical Aortic Valve. NEJM Evid 2023 (Epub) (Rate of valve thrombosis or embolism almost 3x higher in apixaban-treated patients)
  4. Jaffer et al. Rivaroxaban and dabigatran for suppression of mechanical heart valve-induced thrombin generation. Ann Thorac Surg 2019 (Epub) (Combination is more effective than either drug alone in suppressing thrombin formation)
  5. Duan et al. Comparison of Direct Oral Anticoagulants versus Warfarin in Patients with Atrial Fibrillation and Bioprosthetic Heart Valves. Am J Cardiol 2021 (Epub) (DOACs had comparable efficacy, better safety than warfarin)
  6. Guimarães et al. Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve. NEJM 2020;383:2117 (Rivaroxaban non-inferior to warfarin)
  7. Andreas et al. Increased Thromboembolic Events With Dabigatran Compared With Vitamin K Antagonism in Left Ventricular Assist Device Patients A Randomized Controlled Pilot Trial. Circ Heart Fail 2017;10:e003709
  8. Dangas et al. A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement. NEJM 2020;382:120 (Rivaroxaban treatment less effective than antiplatelet Rx and caused more bleeding)
  9. van Ginkel et al. Continuation versus Interruption of Oral Anticoagulation during TAVI. NEJM 2025; 392:438 (No overall difference in adverse events with continuation of anticoagulation, but slightly more bleeding)
  10. Brouwer et al. Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation. NEJM 2020;383:1447(ASA alone led to better outcomes)
  11. Mérie et al. Association of Warfarin Therapy Duration After Bioprosthetic Aortic Valve Replacement With Risk of Mortality, Thromboembolic Complications, and Bleeding. JAMA 2012;308:2118 (Stopping warfarin within 6 mo of valve replacement associated with increased cardiovascular death)
  12. Makkar et al. Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves. NEJM 2015;373:2015 (22/55 patients had reduced leaflet motion after bioprosthetic valve placement; this resolved in all those patients treated with anticoagulation. With editorial)
  13. Chakravarty et al. Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study. Lancet 2017;389:2383 (Subclinical thrombosis is common; warfarin and DOACs more effective than dual antiplatelet therapy in preventing it)
  14. Meurin et al. Low-Molecular-Weight Heparin as a Bridging Anticoagulant Early After Mechanical Heart Valve Replacement. Circulation 2006;113:564
  15. Caldeira et al. Efficacy and safety of low molecular weight heparin in patients with mechanical heart valves: systematic review and meta-analysis. J Thromb Haemost 2014;12:650
  16. Gherli et al.  Comparing Warfarin With Aspirin After Biological Aortic Valve Replacement. A Prospective Study.  Circulation. 2004;110:496
  17. Castilho et al. Thrombolytic therapy or surgery for valve prosthesis thrombosis: systematic review and meta-analysis. J Thromb Haemost 2014;12:1218(Significantly less mortality with thrombolysis, more bleeding and embolic events with thrombolysis; no randomized trials. With editorial commentary)
  18. Özkan et al. Thrombolytic Therapy for the Treatment of Prosthetic Heart Valve Thrombosis in Pregnancy With Low-Dose, Slow Infusion of Tissue-Type Plasminogen Activator. Circulation 2013;128:532
  19. Nijenhuis et al. Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation. NEJM 2020;382:1696(Worse outcomes with adding clopidogrel)

LVADs, ECMO etc

  1. Nascimbene et al. Hemocompatibility and biophysical interface of left ventricular assist devices and total artificial hearts. Blood 2024;143:661
  2. Muslem et al. Acquired coagulopathy in patients with left ventricular assist devices. J Thromb Haemost 2018;16:429
  3. Kreuziger et al. Antithrombotic therapy for left ventricular assist devices in adults: a systematic review. J Thromb Haemost 2015;13:946
  4. Eckman and John. Bleeding and thrombosis in patients with continuous-flow ventricular assist devices. Circulation 2012;125:3038
  5. Susen et al. Circulatory support devices: fundamental aspects and clinical management of bleeding and thrombosis. J Thromb Haemost 2015;13:1757
  6. Nascimbene et al. Acquired von Willebrand syndrome associated with left ventricular assist device. Blood 2016;127:3133
  7. Staessens et al. Thrombus formation during ECMO: Insights from a detailed histological analysis of thrombus composition. J thromb Haemost 2022;20:2058
  8. Helms et al. Anticoagulation in adult patients supported with extracorporeal membrane oxygenation: guidance from the Scientific and Standardization Committees on Perioperative and Critical Care Haemostasis and Thrombosis of the International Society on Thrombosis and Haemostasis. J Thromb Haemost 2023;21:373 (Suggest using UFH with target anti-Xa 0.3-0.5)

Vascular access devices

  1. Fan et al. Preventing arteriovenous shunt failure in hemodialysis patients: a population‐based cohort study. J Thromb Haemost 2019;17:77(ASA reduced access failure rate without increasing major bleeding; warfarin, clopidogrel and aggrenox performed less well. Very large retrospective study using insurance claims database)

Stroke/TIA

  1. Powers WJ. Acute ischemic stroke. NEJM 2020;383:252
  2. O’Toole et al. Hematological causes of acute ischemic stroke in younger individuals. J Thromb Haemost 2025;23:11
  3. Lansberg et al. Antithrombotic and Thrombolytic Therapy for Ischemic Stroke. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e601S
  4. GBD 2016 Lifetime Risk of Stroke Collaborators. Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016. NEJM 2018;379:2429
  5. Paciaroni et al. Timing of anticoagulation therapy in patients with acute ischaemic stroke and atrial fibrillation. Thromb Haemost 2016;116:403
  6. Fischer et al. Early versus Later Anticoagulation for Stroke with Atrial Fibrillation. NEJM 2023;388:2411 (Neither option clearly better; with editorial)
  7. Grosse et al. Prior Anticoagulation and Risk of Hemorrhagic Transformation in Acute Stroke: A Post Hoc Analysis of the PRODAST Study. J Am Heart Assoc 2025 (Epub) (Prior anticoagulation associated with less severe strokes and lower risk of hemorrhagic transformation)
  8. Chang et al. Incidence of Ischemic Stroke in Patients With Asymptomatic Severe Carotid Stenosis Without Surgical Intervention. JAMA 2022;327:1974 (5% incidence of stroke within 5 years)
  9. Saver J. Cryptogenic stroke. NEJM 2016;374:2065
  10. Amarenco P. Transient ischemic attack. NEJM 2020;382:1933
  11. Rothwell et al. Medical treatment in acute and long-term secondary prevention after transient ischaemic attack and ischaemic stroke. Lancet 2011;377:1681
  12. Pezzini et al. Predictors of Long-Term Recurrent Vascular Events After Ischemic Stroke at Young Age. The Italian Project on Stroke in Young Adults. Circulation 2014;129:1668
  13. Amarenco et al. Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke. NEJM 2017;378:2182(Risk of stroke 6.4%/yr over 5 years, did not drop with time)
  14. Hart et al. Predictors of Recurrent Ischemic Stroke in Patients with Embolic Strokes of Undetermined Source and Effects of Rivaroxaban Versus Aspirin According to Risk Status: The NAVIGATE ESUS Trial. J Stroke Cerebrovasc Dis 2019 (Epub)
  15. Kamel et al. Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy: The ARCADIA Randomized Clinical Trial. JAMA 2024 (Epub) (No apparent benefit from apixaban vs ASA)
  16. Del Brutto et al. Predictors of Recurrent Stroke After Embolic Stroke of Undetermined Source in the RE‐SPECT ESUS Trial. J Am Heart Assoc. 2022;11 (Epub)
  17. Geisler et al. Apixaban versus Aspirin for Embolic Stroke of Undetermined Source. NEJM Evid 2023 (Epub) (No difference in outcomes)
  18. Blustin et al. The Association Between Thromboembolic Complications and Blood Group in Patients With Atrial Fibrillation. Mayo Clin Proc 2015;90:216(Blood group O protective)
  19. Stoll et al. Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment. Blood 2008;112:3555
  20. Scott and Smith. Moyamoya Disease and Moyamoya Syndrome. NEJM 2009;360:1226
  21. Cramer and White. Cerebral autosomal dominant arteriopathy (CADASIL). Stat Pearls Nov 1 2017
  22. Tikka et al. CADASIL and CARASIL. Brain Pathol 2014;24:525
  23. Gladstone et al. Atrial fibrillation in patients with cryptogenic stroke. NEJM 2014;370:2467 (16% of patients with cryptogenic stroke aged 55 or older had episodes of AF when monitored for 30 days; editorial)
  24. Israel et al. Detection of atrial fibrillation in patients with embolic stroke of undetermined source by prolonged monitoring with implantable loop recorders. Thromb Haemost 2017; 117:1962(AF found in 25% of patients with embolic stroke of undetermined source)
  25. Sanna et al. Cryptogenic stroke and underlying atrial fibrillation. NEJM 2014;370:2478 (9% of patients 40 and older with cryptogenic stroke found to have AF when monitored for 6 months with an insertable cardiac monitor; incidence rose to 12% at 12 mo; editorial)
  26. Shen et al. Plasma L5 levels are elevated in ischemic stroke patients and enhance platelet aggregation. Blood 2016;127:1336
  27. Hacke et al. Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke. NEJM 2008;359:1317 (more favorable neurologic outcome with thrombolysis, despite higher rate of intracranial hemorrhage)
  28. Li et al. Reteplase versus Alteplase for Acute Ischemic Stroke. NEJM 2024;390:2264 (Reteplase superior)
  29. Thomalia et al. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. NEJM 2018;379:611(Use of alteplase in patients with MRI findings suggesting a recent event resulted in better outcomes than placebo treatment)
  30. Parsons et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. NEJM 2012;366:1099 (Tenecteplase gave superior outcomes)
  31. Campbell et al. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. NEJM 2018;378:1573 (Tenecteplase superior)
  32. Tsai et al. Risk of Bleeding Following Non–Vitamin K Antagonist Oral Anticoagulant Use in Patients With Acute Ischemic Stroke Treated With Alteplase. JAMA Intern Med 2024;184:37 (Prior treatment with DOAC does not increase bleed risk)
  33. Mitchell et al. Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4·5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trial. Lanccet 2022;400:116 (Thrombolysis + thrombectomy superior to thrombectomy alone)
  34. Fischer et al. Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial. Lancet 2022;400:104 (tPA + thrombectomy superior)
  35. Qiu et al. Intravenous Tenecteplase before Thrombectomy in Stroke.  NEJM 2025;393:139 (Better outcomes than with thrombectomy alone)
  36. Jovin et al. Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysis. Lancet 2022;399:249 (Thrombectomy up to 24 h after stroke appears beneficial)
  37. Bendszus et al. Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial. Lancet 2023;402:1753
  38. van der Steen et al. Safety and efficacy of aspirin, unfractionated heparin, both, or neither during endovascular stroke treatment (MR CLEAN-MED): an open-label, multicentre, randomised controlled trial. Lancet 2022;399:1059 (Increased risk of ICH with either drug)
  39. IST-3 Collaborative Group. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet 2012;379:2352
  40. Anderson et al. Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke. NEJM 2016;374:2313(Outcomes similar with 0.6 mg/kg vs 0.9 mg/kg altepase in Asian patients; with editorial)
  41. Kim et al. Treatment With Tissue Plasminogen Activator in the Golden Hour and the Shape of the 4.5-Hour Time-Benefit Curve in the National United States Get With The Guidelines-Stroke Population. Circulation 2017;135:128(Treatment within 60 minutes associated with best outcomes)
  42. Khatri et al. Effect of Alteplase vs Aspirin on Functional Outcome for Patients With Acute Ischemic Stroke and Minor Nondisabling Neurologic Deficits. The PRISMS Randomized Clinical Trial. JAMA 2018;320:156(No difference in outcome at 90 days)
  43. Emberson et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014;384:1929(Treatment within 4-5 h beneficial regardless of age or stroke severity)
  44. Ma et al. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. NEJM 2019;380:1795(Less severe neuro deficits, more ICH with thrombolysis 4.5-9 hours after stroke onset; with editorial)
  45. Campell et al. Extending thrombolysis to 4·5–9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data. Lancet 2019;394:139
  46. Thomalla et al. Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data. Lancet 2020;396:1574 (More favorable outcomes with altepase, but more bleeding)
  47. Xiong et al. Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without Thrombectomy. NEJM 2024;391:203 (Better neurologic outcomes, more ICH, similar mortality with thrombolysis vs standard care; with editorial)
  48. Zhu et al. Combination of the Immune Modulator Fingolimod With Alteplase in Acute Ischemic Stroke. A Pilot Trial. Circulation 2015;132:1104(25 pts; treatment appeared beneficial)
  49. Xian et al. Use of Intravenous Recombinant Tissue Plasminogen Activator in Patients With Acute Ischemic Stroke Who Take Non–Vitamin K Antagonist Oral Anticoagulants Before Stroke. Circulation 2017;135:1024(rt-PA “reasonably well tolerated” in this population)
  50. Kam et al. Association of Recent Use of Non–Vitamin K Antagonist Oral Anticoagulants With Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase. JAMA 2022;337:760 (Recent DOAC use did not increase risk of IC hemorrhage)
  51. Berkhemer et al. A randomized trial of intraarterial treatment for acute ischemic stroke. NEJM 2015;372:11(Mechanical or thrombolytic intra-arterial treatment appears superior to standard care)
  52. van den Berg et al. Two-Year Outcome after Endovascular Treatment for Acute Ischemic Stroke. NEJM 2017;376:1341 (Mechanical thrombectomy superior to medical management)
  53. Yoshimura et al. Endovascular Therapy for Acute Stroke with a Large Ischemic Region. NEJM 2022;386:1303
  54. Martins et al. Thrombectomy for Stroke in the Public Health Care System of Brazil. NEJM 2020;383:2316 (Thrombectomy improved outcomes vs medical management)
  55. Sarraj et al. Trial of Endovascular Thrombectomy for Large Ischemic Strokes. NEJM 2023;388:1259 (Better functional outcomes, similar mortality, more vascular complications with thrombectomy; with editorial)
  56. Huo et al. Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct. NEJM 2023;388:1272 (Better functional outcomes, more intrancranial bleeds with thrombectomy; with editorial)
  57. LeCouffe et al. A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke. NEJM 2021;385:1833 (Altepase prior to thrombectomy appears superior to thrombectomy alone)
  58. Xian et al. Risks of Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Receiving Warfarin and Treated With Intravenous Tissue Plasminogen Activator. JAMA 2012;307:2600(No increase in ICH rate for patients with INR 1.7 or less)
  59. Su et al. Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke. Nat Med 2008;14:731 (Imatinib reduces hemorrhagic complications following tPA treatment of stroke in mice)
  60. Saver et al. Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone in Stroke. NEJM 2015;372:2285(with editorial)
  61. Jovin et al. Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke. NEJM 2015;372:2296(with editorial)
  62. Badhiwala et al. Endovascular Thrombectomy for Acute Ischemic Stroke. A Meta-analysis. JAMA 2015;314:1832 (Thrombectomy associated with improved functional outcome vs standard care with tPA)
  63. Albers et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. NEJM 2018;378:708 (Better outcomes when thrombectomy added to standard medical therapy)
  64. Tao et al. Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion. NEJM 2022:1361 (Better functional outcomes but more complications with thrombectomy)
  65. Zinkstock et al. Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial. Lancet 2013;380:26(Higher risk of ICH, no improvement in neuro outcomes if ASA given prior to 24h after tPA)
  66. Chimowitz et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. NEJM 2005;352:1305(Warfarin caused more bleeding and was no more effective in preventing stroke, brain hemorrhage, or death from vascular causes than aspirin)
  67. Sacco et al. Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke. NEJM 2008;359:1238(Combined risk of stroke and major bleeding similar in both groups)
  68. SPS3 Investigators. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. NEJM 2012;367:817(Adding clopidogrel did not reduce stroke risk, increased risk of bleedig & death)
  69. Wang et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. NEJM 2013;369:11 (Adding clopidogrel to aspirin reduced stroke risk by about 30%, without increasing bleeding risk; with editorial)
  70. Hao et al. Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis. BMJ 2018;363:k5108(Clopidogrel + ASA given within 24 hours superior to ASA alone in preventing subsequent stroke)
  71. Bath et al. Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial. Lancet 2018;391:850(Triple antiplatelet therapy did not reduce risk of recurrence but did cause more bleeding)
  72. Johnston et al. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. NEJM 2018;379:215(Adding clopidogrel to ASA decreased rate of major ischemic events from 6.5% to 5% and increased rate of major bleeding from 0.4% to 0.9%; with editorial)
  73. Gao et al. Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke. NEJM 2023;389:2413 (DAPT lowers risk of recurrent stroke with modest increase in bleed risk vs ASA alone)
  74. Johnston et al. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. NEJM 2016;375:35(Ticagrelor not superior to ASA)
  75. Johnston et al. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. NEJM 2020;383:207(THALES trial; modest improvement in stroke+death incidence @ 30 days, more bleeding with adding ticagrelor. With editorial)
  76. Zi et al. Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion. NEJM 2023;388:2025 (Better outcomes with tirofiban than ASA; with editorial)
  77. Wu et al. Early risk of stroke after transient ischemic attack. A systematic review and meta-analysis. Arch Intern Med 2007;167:2417 (9% risk of stroke within 30 days)
  78. Bos et al. Incidence and prognosis of transient neurological attacks. JAMA 2007;298:2877
  79. Paciaroni et al. Efficacy and safety of anticoagulants in the prevention of venous thromboembolism in patients with acute cerebral hemorrhage: a meta-analysis of controlled studies. J Thromb Haemost 2011;9:893(Significant reduction in PE, non-significant decrease in mortality, increased risk of enlarging hematoma)
  80. Sharma et al. Stroke Outcomes in the Cardiovascular OutcoMes for People using Anticoagulation StrategieS (COMPASS) Trial. Circulation 2019;139:1134 (Rivaroxaban + ASA lowered stroke rate by 40% vs ASA alone in patients with stable coronary or peripheral vascular disease)
  81. Diener et al. Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source. NEJM 2019;380:1906 (Dabigatran no more effective than ASA, caused more bleeding)
  82. Hart et al. Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source. NEJM 2018;378:2191 (Rivaroxaban 15 mg daily not superior to ASA 100 mg/day, caused more bleeding)

PFO and stroke

  1. De Rosa et al. Percutaneous Closure Versus Medical Treatment in Stroke Patients With Patent Foramen Ovale: A Systematic Review and Meta-analysis. Ann Intern Med 2018;168:343
  2. Kizer and Devereux.  Patent foramen ovale in young adults with unexplained stroke.  NEJM 2005;353:2361
  3. Handke et al. Patent Foramen Ovale and Cryptogenic Stroke in Older Patients. NEJM 2007;:357:2262
  4. Anzola et al. Patent foramen ovale (PFO) and cryptogenic stroke. J Thromb Haemost 2010;8:1675
  5. Furlan et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. NEJM 2012;366:991(No advantage to closure vs medical therapy)
  6. Meier et al. Percutaneous Closure of Patent Foramen Ovale in Cryptogenic Embolism. NEJM 2013;368:1083(No advantage to closure vs medical therapy)
  7. Carroll et al. Closure of Patent Foramen Ovale versus Medical Therapy after Cryptogenic Stroke. NEJM 2013;368:1092(Possible advantage to closure; with editorial)
  8. Ng et al. Association of Preoperatively Diagnosed Patent Foramen Ovale With Perioperative Ischemic Stroke. JAMA 2018;319:452(Perioperatve stroke risk 6-fold higher in patients with PFO)

Peripheral vascular disease

  1. Alonso-Coello et al. Antithrombotic Therapy in Peripheral Artery Disease. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e669S
  2. Cameron et al. Antithrombotic therapy in abdominal aortic aneurysm: beneficial or detrimental? Blood 2018;132:2619
  3. Bonaca et al. Rivaroxaban in Peripheral Artery Disease after Revascularization. NEJM 2020;382:1994(Rivaroxaban 2.5 mg bid modestly reduced incidence of vascular events vs ASA, no difference in bleeding)
  4. Bauersachs et al. Total Ischemic Event Reduction with Rivaroxaban after Peripheral Arterial Revascularization in the VOYAGER PAD Trial. J Am Coll Cardiol 2021 (Epub)
  5. Hiatt et al. Rivaroxaban and Aspirin in Peripheral Artery Disease Lower Extremity Revascularization. Impact of Concomitant Clopidogrel on Efficacy and Safety. Circulation 2020;142:2219 (<30 day course of clopidogrel safer)
  6. Creager et al. Acute limb ischemia. NEJM 2012;366:2198
  7. Andersen et al. Upper limb arterial thromboembolism: a systematic review on incidence, risk factors, and prognosis, including a meta-analysis of risk-modifying drugs. J Thromb Haemost 2013;11:836