University of Wisconsin Hematology

Treatment of bleeding disorders

(see also Transfusion Medicinesection)

  1. Callaghan et al. Novel therapeutics for hemophilia and other bleeding disorders. Blood 2018;132:23
  2. Mannucci and Levi. Prevention and treatment of major blood loss. NEJM 2007;356:2301
  3. Johansson et al. How I treat patients with massive hemorrhage. Blood 2014;124:3052(Discusses role of TEG and antifibrinolytic Rx)
  4. Cannon JW. Hemorrhagic shock. NEJM 2018;378:370
  5. Baker and O’Donnell. How I treat bleeding disorder of unknown cause. Blood 2021;138:1795
  6. Pavord and Maybury. How I treat postpartum hemorrhage. Blood 2015;125:2759
  7. Ragni MV. The old and new: PCCs, VIIa, and long-lasting clotting factors for hemophilia and other bleeding disorders. Hematology 2013:44
  8. Laan et al. DDAVP response and its determinants in bleeding disorders: a systematic review and meta-analysis. Blood 2025;145:1814
  9. Al Arishi et al. Desmopressin to prevent and treat bleeding in pregnant women with an inherited bleeding disorder: a systematic literature review. J Thromb Haemost 2024;22:126
  10. Desborough et al. Desmopressin for treatment of platelet dysfunction and reversal of antiplatelet agents: a systematic review and meta-analysis of randomized controlled trials. J Thromb Haemost 2017;15:263
  11. Colucci et al. The effect of desmopressin on platelet function: a selective enhancement of procoagulant COAT platelets in patients with primary platelet function defects. Blood 2014;123:1905
  12. van den Brink et al.Effectiveness of prothrombin complex concentrate for the treatment of bleeding: A systematic review and meta‐analysis. J Thromb Haemost 2020; 18:2457(Possible benefit in trauma and cardiac surgery)
  13. Hoots WK. Challenges in the Therapeutic Use of a “So-Called” Universal Hemostatic Agent: Recombinant Factor VIIa. Hematology 2006;426
  14. Roberts et al. The use of recombinant factor VIIa in the treatment of bleeding disorders. Blood 2004;104:3858
  15. Mayer et al. Recombinant Activated Factor VII for Acute Intracerebral Hemorrhage.  NEJM 2005;352:777
  16. Mayer et al. Efficacy and Safety of Recombinant Activated Factor VII for Acute Intracerebral Hemorrhage. NEJM 2008;358:2127(Treatment with rFVIIa reduced hematoma growth but did not improve survival or functional outcome; with editorial)
  17. O’Connell et al. Thromboembolic Adverse Events After Use of Recombinant Human Coagulation Factor VIIa. JAMA 2006;295:293
  18. Levi et al. Safety of r ecombinant activated factor VII in randomized clinical trials. NEJM 2010;363:1791(Increased incidence of arterial thromboembolism, particularly in elderly patients. See also the accompanying editorial)
  19. Logan et al. Off-Label Use of Recombinant Factor VIIa in U.S. Hospitals: Analysis of Hospital Records. Ann Intern Med 2011;154:516(97% of use off-label)
  20. Yank et al. Systematic Review: Benefits and Harms of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications. Ann Intern Med 2011;154:529(No evidence of reduced mortality, increased risk of thromboembolism)
  21. Karkouti et al. Comprehensive Canadian Review of the Off-Label Use of Recombinant Activated Factor VII in Cardiac Surgery. Circulation 2008;118:331
  22. Lavigne-Lissalde et al. Recombinant human FVIIa for reducing the need for invasive second-line therapies in severe refractory postpartum hemorrhage: a multicenter, randomized, open controlled trial. J Thromb Haemost 2015;13:520(rVIIa use reduced need for “second-line” therapies; 5% of recipients had thrombotic events)
  23. Ekezue et al. Clotting factor product administration and same-day occurrence of thrombotic events, as recorded in a large healthcare database during 2008–2013. J Thromb Haemost 2015;13:2168(Off-label use of factor IX concentrate and rVIIa associated with increased risk of thrombosis)
  24. Levy and Goodnough. How I use fibrinogen replacement therapy in acquired bleeding. Blood 2015;125:1387
  25. Bilicen et al. Effect of Fibrinogen Concentrate on Intraoperative Blood Loss Among Patients With Intraoperative Bleeding During High-Risk Cardiac Surgery. A Randomized Clinical Trial. JAMA 2017;317:738(Raising fibrinogen to 250 mg/dL did not reduce intraoperative bleeding, associated with more thrombotic complications)
  26. Falanga and Rickles. Management of thrombohemorrhagic syndromes (THS) in hematologic malignancies. Hematology 2007:165
  27. Chen et al. Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia. NEJM 2023;389:1649 (With editorial)
  28. Yashigi et al. Gastrointestinal Angiodysplasia before and after Treatment of Severe Aortic Stenosis. NEJM 2023;389:1530

Antifibrinolytic therapy

  1. McQuilten et al. When to use tranexamic acid for the treatment of major bleeding? J Thromb Haemost 2024;22:581
  2. CRASH-2 Collaborators.The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet 2011;377:1096 (Treatment within 3 hours of injury reduces death from bleeding)
  3. CRASH-3 Collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial. Lancet 2019;394:1713 (Treatment within 3 h of injury reduces death rate from head injury in patients with mild or moderate injury)
  4. The PATCH-Trauma Investigators and the ANZICS Clinical Trials Group. Prehospital Tranexamic Acid for Severe Trauma. NEJM 2023;389:127 (Modest short-term benefit, no difference in functional outcome at 6 mo. With editorial)
  5. Gayet-Ageron et al. Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients. Lancet 2018;391:125 (Immediate treatment improved survival by over 70%; benefit decreased by 10% for every 15 min of delay in treatment)
  6. Myles et al. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery. NEJM 2017;376:136 (Tranexamic acid reduced bleeding risk and transfusion requirements, and did not increase thrombotic risk; it was associated with a higher risk of seizures)
  7. Shi et al. Effect of High- vs Low-Dose Tranexamic Acid Infusion on Need for Red Blood Cell Transfusion and Adverse Events in Patients Undergoing Cardiac Surgery. The OPTIMAL Randomized Clinical Trial. JAMA 2022;328:336 (“Modest” benefit with high-dose TXA)
  8. Devereaux et al. Tranexamic Acid in Patients Undergoing Noncardiac Surgery. NEJM 2022;386:1986 (25% lower bleeding rate with TXA, small increase in cardiovascular events; with editorial)
  9. Chornenki et al. Risk of venous and arterial thrombosis in non-surgical patients receiving systemic tranexamic acid: A systematic review and meta-analysis. Thromb Res 2019;179:81(No increase in thrombotic events, 8% reduction in all-cause mortality with TXA use)
  10. WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet 2017;389:2081(TXA given within 3 hours of delivery to women with postpartum hemorrhage reduced maternal mortality by 30%; no increase in thrombotic complications. With editorial)
  11. Sentilhes et al. Tranexamic Acid for the Prevention of Blood Loss after Vaginal Delivery. NEJM 2018;379:731(No significant decrease in blood loss with treatment)
  12. Sentilhes et al. Tranexamic Acid for the Prevention of Blood Loss after Cesarean Delivery. NEJM 2021;384:1623(Modest “biologic” benefit from TXA therapy, no significant clinical benefit)
  13. Pacheco et al. Tranexamic Acid to Prevent Obstetrical Hemorrhage after Cesarean Delivery. NEJM 2023;388:1365 (No reduction in transfusion needs or maternal death)
  14. Sprigg et al. Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet 2018;391:2107(TXA treatment reduced early deaths and SAEs but did not improve functional status at 90 days)
  15. HALT-IT Trial Collaborators. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet 2020;395:10241 (No reduction in bleeding deaths, slight increase in VTE risk)
  16. Longstaff and Locke. Increased urokinase and consumption of α2‐antiplasmin as an explanation for the loss of benefit of tranexamic acid after treatment delay. J Thromb Haemost 2019;17:195
  17. Wang et al. The antifibrinolytic and anti‐inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial. J Thromb Haemost 2018;16:2442(TXA reduced postop blood loss and reduced inflammation, helped with early rehab)
  18. Chornenki et al. Risk of venous and arterial thrombosis in non-surgical patients receiving systemic tranexamic acid: A systematic review and meta-analysis. Thromb Res 2019;179:81(Treatment decreases all-cause mortatlity by 8%, with no increase in thrombotic risk)