University of Wisconsin Hematology

Acquired bleeding disorders

Vitamin K deficiency/vitamin K antagonists

  1. Alperin J. Coagulopathy caused by vitamin K deficiency in critically ill, hospitalized patients. JAMA 1987; 258:1916
  2. van der Meer et al. Bleeding complications in oral anticoagulant therapy. An analysis of risk factors. Arch Intern Med 1993;153:1557
  3. Weibert et al.  Correction of Excessive Anticoagulation with Low-Dose Oral Vitamin K1. Ann Intern Med 1997;126:959
  4. van Rein et al. Vitamin K1 in oral solution or tablets: a crossover trial and two randomized controlled trials to compare effects. J Thromb Haemost 2014;12:2017(Tablets as effective as solution)
  5. Sarin et al.  Prolonged coagulopathy related to superwarfarin overdose. Ann Intern Med 2005;142:156
  6. Schulman and Furie. How I treat poisoning with vitamin K antagonists. Blood 2015;125:438(Superwarfarin and warfarin poisoning)
  7. Kelkar et al. An Outbreak of Synthetic Cannabinoid–Associated Coagulopathy in Illinois. NEJM 2018;379:1216
  8. Arepally and Ortel. Bad weed: synthetic cannabinoid-associated coagulopathy. Blood 2019;133:902
  9. Yip et al. Vitamin K1 Treatment Duration in Patients with Brodifacoum Poisoning. NEJM 2020;382:1764(Suggests using serial brodifacoum levels to calculate elimination half-life)
  10. Chen et al. A cell-based high-throughput screen identifies drugs that cause bleeding disorders by off-targeting the vitamin K cycle. Blood 2020;136:898(Identified 9 drugs that can cause vit K deficiency)

Liver disease

  1. Lisman T. How to assess hemostasis in patients with severe liver disease. Hematology Am Soc Hematol Educ Program (2023): 267
  2. Northrup et al. Treatment of bleeding in patients with liver disease. J Thromb Haemost 2021;109:1644
  3. Lisman et al. The concept of rebalanced hemostasis in patients with liver disease: Communication from the ISTH SSC working group on hemostatic management of patients with liver disease. J Thromb Haemost 2021;19:1116
  4. Sinegre et al. Intraindividual variability over time of thrombin generation in patients with cirrhosis. J Thromb Haemost 2023;21:1441 (Unstable thrombin generation profile correlates with severity of liver disease)
  5. Roberts et al. Periprocedural management of abnormal coagulation parameters and thrombocytopenia in patients with cirrhosis: Guidance from the SSC of the ISTH. J Thromb Haemost 2022;20:39
  6. 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
  7. Bissonnette et al. Predicting bleeding after liver biopsy using comprehensive clinical and laboratory investigations: A prospective analysis of 302 procedures. J Thromb Haemost 2022;20:2786 (Hemostatic parameters do not predict bleeding risk)
  8. Tripodi and Mannucci. The coagulopathy of chronic liver disease. NEJM 2011;365:147
  9. Lisman and Porte. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood 2010; 116:878
  10. Dabbagh et al. Coagulopathy Does Not Protect Against Venous Thromboembolism in Hospitalized Patients With Chronic Liver Disease. Chest 2010;137:1145
  11. Ambrosino et al. The risk of venous thromboembolism in patients with cirrhosis. A systematic review and meta-analysis. Thromb Haemost 2017;117:139 (1.5-2-fold increase in risk of VTE)
  12. De Pietri et al. Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy. A randomized controlled trial. Hepatology 2015 (Epub)(Less than 10% of TEG-guided group got blood products, with no bleeding complications, vs 100% of patients treated based on INR and plt count)
  13. Sinegre et al. Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis. J Thromb Haemost 2018;16:1132
  14. von Meijenfeldt et al. Prophylactic fresh frozen plasma and platelet transfusion have a prothrombotic effect in patients with liver disease. J Thromb Haemost 2021;19:664
  15. Afzal et al. Different risks of hemorrhage in patients with elevated international normalized ratio from chronic liver disease versus warfarin therapy, a population-based retrospective cohort study. J Thromb Haemost 2022;20:1610 (Lower bleeding risk at high INRs in liver disease vs warfarin treatment)

Autoimmune clotting factor deficiency (factor VIII and other antibodies)

  1. Arruda et al. Immune complications and their management in inherited and acquired bleeding disorders. Blood 2022;140:1075
  2. Ma and Carrizosa. Acquired Factor VIII Inhibitors: Pathophysiology and Treatment. Hematology 2006;426
  3. Baglin et al. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors’ Organisation. Blood 2007; 109:1870(1 case/1.5 million people/yr; median age 78; 9% died of bleeding; 20% relapse rate)
  4. Knoebl et al. Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). J Thromb Haemost 2012;10:622
  5. Holstein et al Bleeding and response to hemostatic therapy in acquired hemophilia A: results from the GTH-AH 01/2010 study. Blood 2020;136:279
  6. Baudo et al. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry. Blood 2012;120:39 (Both rVIIa and activated prothrombin complex concentrate over 90% effective)
  7. Collins et al. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). Blood 2012;120:47 (Corticosteroids plus cyclophosphamide more effective than steroids alone or rituximab)
  8. Tiede et al. Prognostic factors for remission of and survival in acquired hemophilia A (AHA): results from the GTH-AH 01/2010 study. Blood 2015;125:1091 (FVIII activity and inhibitor titer at presentation have prognostic utility)
  9. Tiede et al. Anti–factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study. Blood 2016;127:2289
  10. Donohoe and Levine. Acquired factor V inhibitor after exposure to topical human thrombin related to an otorhinolaryngological procedure. J Thromb Haemost 2015;13:1787
  11. Muszbek et al. Auto- and alloantibodies against factor XIII: laboratory diagnosis and clinical consequences J Thromb Haemost 2018;16:822
  12. Tiede et al. Should emicizumab be used in patients with acquired hemophilia A? J Thromb Haemost 2021;19:637(Maybe)
  13. Knoebl et al. Emicizumab for the treatment of acquired hemophilia A. Blood 2021;137:410 (Effective, avoids prolonged need for bypassing agent)
  14. Shima et al. A prospective, multicenter, open-label phase III study of emicizumab prophylaxis in patients with acquired hemophilia A. J Thromb Haemost 2023;21:534 (Safe and effective)
  15. Hart et al. Emicizumab versus immunosuppressive therapy for the management of acquired hemophilia A. J Thromb Haemost 2024;22:2692 (Early emicizumab treatment reduced bleeding rate and improved survival)
  16. Simon et al. Combined immunosuppression for acquired hemophilia A: CyDRi is a highly effective low-toxicity regimen. Blood 2022;140:1983
  17. Liu et al. Anti-CD38 antibody for refractory acquired hemophilia A. J Thromb  Haemost 2023;21:1515 (Daratumumab effective in 4/4 patients)
  18. Wang et al. Single-dose rituximab plus glucocorticoid versus cyclophosphamide plus glucocorticoid in patients with newly diagnosed acquired hemophilia A: A multicenter, open-label, randomized noninferiority trial. Am J Hematol 2024;99:28

Acquired von Willebrand disease

  1. Frere et al. Acquired von Willebrand syndrome during extracorporeal membrane oxygenation support: a comprehensive review of current evidence: communication from the ISTH SSC on perioperative and critical care thrombosis and hemostasis. J Thromb Haemost 2024;22:2608
  2. Blackshear et al. Remission of recurrent gastrointestinal bleeding after septal reduction therapy in patients with hypertrophic obstructive cardiomyopathy-associated acquired von Willebrand syndrome. J Thromb Haemost 2015;13:191
  3. Blackshear et al. Shear stress-associated acquired von Willebrand syndrome in patients with mitral regurgitation. J Thromb Haemost 2014;12:1966
  4. Lavin et al. Lenalidomide as a novel treatment for refractory acquired von Willebrand syndrome associated with monoclonal gammopathy. J Thromb Haemost 2016;14:1200
  5. Nascimbene et al. Acquired von Willebrand syndrome associated with left ventricular assist device. Blood 2016;127:3133
  6. Van Belle et al. Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement. NEJM 2016;375:335 (VWF multimer defects following TAVR associated with aortic regurgitation and higher mortality)
  7. Buguzzi et al. How I treat gastrointestinal bleeding in congenital and acquired von Willebrand disease. Blood 2020;136:1125

Trauma and massive transfusion

  1. Hess J. Blood and coagulation support in trauma care. Hematology 2007:187
  2. White et al. Early hemostatic responses to trauma identified with hierarchical clustering analysis. J Thromb Haemost 2015;13:978(Lower fibrinogen, more fibrinolysis, more bleeding in most severely injured patients)
  3. Juffermans et al. Towards patient‐specific management of trauma hemorrhage: the effect of resuscitation therapy on parameters of thromboelastometry. J Thromb Haemost 2019;17:441
  4. Innerhoffer et al. Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial. Lancet Haematol 2017;4:e258(Fibrinogen supplementation guided by thromboelastometry superior to FFP treatment; with editorial)
  5. Cardenas et al. Platelet transfusions improve hemostasis and survival in a substudy of the prospective, randomized PROPPR trial. Blood Adv 2018;2:1696

Complications of pregnancy

  1. Bienstock et al. Postpartum hemorrhage. NEJM 2021;384:1635(<1% of cases due to hemostatic defect)
  2. Gallos et al. Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage. NEJM 2023;389:11
  3. Henriquez et al. Management of postpartum hemorrhage: how to improve maternal outcomes? J Thromb Haemost 2018;16:1523
  4. Collins et al. Fibrin-based clot formation as an early and rapid biomarker for progression of postpartum hemorrhage: a prospective study. Blood 2014;124:1727(Viscoelastic measurements predict progression to severe hemorrhage)
  5. Wei et al. Clinical diagnosis and treatment of acute fatty liver of pregnancy: A literature review and 11 new cases. J Obst Gyn Res 2010; 36:751
  6. Gillissen et al. Coagulation parameters during the course of severe postpartum hemorrhage: a nationwide retrospective cohort study. Blood Adv 2018;2:2433(Fibrinogen < 2 g/L predicted poor outcome)
  7. de Lloyd et al. Acute obstetric coagulopathy during postpartum hemorrhage is caused by hyperfibrinolysis and dysfibrinogenemia: an observational cohort study. J Thromb Haemost 2023;21:862
  8. Castle et al. Outcomes and management of pregnancy in women with bleeding disorder of unknown cause. J Thromb Haemost 2022;20:2519  (Prophylaxis with TXA, DDAVP or platelet transfusion reduced incidence of postpartum hemorrhage from 78% to 36%)

Other/general

  1. Bannow and Konkle.  How I approach bleeding in hospitalized patients. Blood 2023;142:761
  2. Konkle BA. Acquired disorders of platelet function. Hematology 2011:391
  3. Bartoszko and Karkouti. Managing the coagulopathy associated with cardiopulmonary bypass. J Thromb Haemost 2021;19:617
  4. Meijer et al. Association of Risk of Abnormal Bleeding With Degree of Serotonin Reuptake Inhibition by Antidepressants. Arch Intern Med 2004;164:2357
  5. Jackson et al. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood 2019;133:906
  6. Saes et al. Hemorrhagic disorders of fibrinolysis: a clinical review. J Thromb Haemost 2018;16:1498
  7. Kolev and Longstaff. Bleeding related to disturbed fibrinolysis. Br J Haematol 2016;175:12
  8. Noris and Remuzzi. Uremic bleeding: closing the circle after 30 years of controversies? Blood 1999;94:2569
  9. Elbers et al. The influence of thyroid function on the coagulation system and its clinical consequences. J Thromb Haemost 2018;16:634
  10. Hunt BJ. Bleeding and coagulopathies in critical care. NEJM 2014;370:847
  11. Weiss et al. Acquired platelet GPVI receptor dysfunction in critically ill patients with sepsis. Blood 2021;137:3105
  12. Biancari et al. Prediction of severe bleeding after coronary surgery: the WILL-BLEED Risk Score. Thromb Haemost 2017; 117: 429
  13. Müller et al. Fresh frozen plasma transfusion fails to influence the hemostatic balance in critically ill patients with a coagulopathy. J Thromb Haemost 2015;13:989(12 ml/kg FFP raised clotting factor levels by 10-12% but did not enhance thrombin generation in non-bleeding critically ill patients with a long INR)
  14. Ocak et al. Mortality due to bleeding, myocardial infarction and stroke in dialysis patients. J Thromb Haemost 2018;16:1953
  15. Sachetto and Mackman. Modulation of the mammalian coagulation system by venoms and other proteins from snakes, arthropods, nematodes and insects. Thromb Res 2019;178:145
  16. Gutiérrez et al. Progress and challenges in the field of snakebite envenoming therapeutics. Annu Rev Pharmacol Toxicol 2025;65:465.
  17. Kern and Gardner. Mucocutaneous manifestations of scurvy. NEJM 2020;382:e56
  18. Bodilsen et al. Association of Lumbar Puncture With Spinal Hematoma in Patients With and Without Coagulopathy. JAMA 2020;324:1419(Prolonged INR or PTT, but not thrombocytopenia, increased rsk of traumatic LP)
  19. Sheth KN. Spontaneous Intracerebral Hemorrhage. NEJM 2022;387:1589
  20. Mehic et al. Risk factors for future bleeding in patients with mild bleeding disorders: longitudinal data from the Vienna Bleeding Biobank. J Thromb Haemost 2023;21:1757