Treatment of bleeding and perioperative management in hemophilia A and B
- W Keith Hoots, MD
W Keith Hoots, MD
- Director, Division of Blood Diseases and Resources
- National Heart, Lung and Blood Institute
- National Institutes of Health, Bethesda, Maryland
- Amy D Shapiro, MD
Amy D Shapiro, MD
- Medical Director
- Indiana Hemophilia and Thrombosis Center
- Section Editors
- Donald H Mahoney, Jr, MD
Donald H Mahoney, Jr, MD
- Section Editor — Pediatric Hematology
- Professor of Pediatrics
- Baylor College of Medicine
- Lawrence LK Leung, MD
Lawrence LK Leung, MD
- Editor-in-Chief — Hematology
- Section Editor — Disorders of Hemostasis and Coagulation
- Professor of Medicine
- Stanford University School of Medicine
Hemophilia A (factor VIII [factor 8] deficiency) and hemophilia B (factor IX [factor 9] deficiency) are X-linked coagulation factor disorders associated with bleeding of variable severity, from life-threatening to clinically silent. The availability of factor replacement products has dramatically improved care for individuals with these conditions. However, patients do present with acute bleeding symptoms that require rapid treatment, and planning is required for patients undergoing surgery or invasive procedures.
This topic review discusses the treatment of bleeding and perioperative management for individuals with hemophilia A and B. Our approach is consistent with the World Federation of Hemophilia Guideline updated in 2012 (available at http://www.wfh.org/en/resources/wfh-treatment-guidelines) .
The diagnosis, routine prophylaxis, obstetrical management, inhibitor eradication, and genetics of hemophilia are discussed in separate topic reviews:
●Diagnosis – (See "Clinical manifestations and diagnosis of hemophilia".)
●Obstetrical issues – (See "Clinical manifestations and diagnosis of hemophilia", section on 'Obstetrical issues'.)
- Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia 2013; 19:e1.
- Vanderhave KL, Caird MS, Hake M, et al. Musculoskeletal care of the hemophiliac patient. J Am Acad Orthop Surg 2012; 20:553.
- Hoots KW. Emergency management of hemophilia. In: Textbook of Hemophilia, 3rd ed, Lee CA, Berntorp EE, Hoots WK (Eds), John Wiley & Sons, Ltd, 2014. p.463.
- Berntorp E, Shapiro AD. Modern haemophilia care. Lancet 2012; 379:1447.
- Ljung RC, Knobe K. How to manage invasive procedures in children with haemophilia. Br J Haematol 2012; 157:519.
- Fowler H, Lacey R, Keaney J, et al. Emergency and out of hours care of patients with inherited bleeding disorders. Haemophilia 2012; 18:e126.
- http://www.ukhcdo.org/wp-content/uploads/2015/12/EmergencyCareStandardsFinalVersionJune2009-For-Website.pdf (Accessed on August 16, 2016).
- Hoots WK. Emergency management in hemophilia. In: Textbook of Hemophilia, 2nd ed, Lee CA, Berntorp EE, Hoots WK (Eds), Wiley-Blackwell, Oxford, UK 2010. p.394.
- Gilchrist GS, Piepgras DG, Roskos RR. Neurologic Complications in Hemophilia. In: Hemophilia in the Child and Adult, Hilgartner MW, Pochedly C (Eds), Raven Press, New York 1989. p.45.
- Schulman S, Varon D, Keller N, et al. Monoclonal purified F VIII for continuous infusion: stability, microbiological safety and clinical experience. Thromb Haemost 1994; 72:403.
- Martinowitz UP, Schulman S. Continuous infusion of factor concentrates: review of use in hemophilia A and demonstration of safety and efficacy in hemophilia B. Acta Haematol 1995; 94 Suppl 1:35.
- Hay CR, Doughty HI, Savidge GF. Continuous infusion of factor VIII for surgery and major bleeding. Blood Coagul Fibrinolysis 1996; 7 Suppl 1:S15.
- Schulman S, Wallensten R, White B, Smith OP. Efficacy of a high purity, chemically treated and nanofiltered factor IX concentrate for continuous infusion in haemophilia patients undergoing surgery. Haemophilia 1999; 5:96.
- Yamamoto M, Nakadate H, Iguchi U, et al. [Successful management of neurosurgical procedures with continuous infusion of recombinant factor IX in a child with hemophilia B]. Rinsho Ketsueki 2013; 54:300.
- Henrard S, Speybroeck N, Hermans C. Body weight and fat mass index as strong predictors of factor VIII in vivo recovery in adults with hemophilia A. J Thromb Haemost 2011; 9:1784.
- Simpson ML, Valentino LA. Management of joint bleeding in hemophilia. Expert Rev Hematol 2012; 5:459.
- Kisker CT, Burke C. Double-blind studies on the use of steroids in the treatment of acute hemarthrosis in patients with hemophilia. N Engl J Med 1970; 282:639.
- Moore MF, Tobase P, Allen DD. Meta-analysis: outcomes of total knee arthroplasty in the haemophilia population. Haemophilia 2016; 22:e275.
- Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007; 357:535.
- Paton RW, Evans DI. Silent avascular necrosis of the femoral head in haemophilia. J Bone Joint Surg Br 1988; 70:737.
- Franchini M, Favaloro EJ, Lippi G. Mild hemophilia A. J Thromb Haemost 2010; 8:421.
- Poon MC, Aledort LM, Anderle K, et al. Comparison of the recovery and half-life of a high-purity factor IX concentrate with those of a factor IX complex concentrate. Factor IX Study Group. Transfusion 1995; 35:319.
- Powell JS, Pasi KJ, Ragni MV, et al. Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med 2013; 369:2313.
- Brand B, Gruppo R, Wynn TT, et al. Efficacy and safety of pegylated full-length recombinant factor VIII with extended half-life for perioperative haemostasis in haemophilia A patients. Haemophilia 2016; 22:e251.
- Mahlangu J, Powell JS, Ragni MV, et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood 2014; 123:317.
- Kavakli K, Kurugöl Z, Göksen D, Nisli G. Should hemophiliac patients be circumcised? Pediatr Hematol Oncol 2000; 17:149.
- Rosner F. Hemophilia in the Talmud and rabbinic writings. Ann Intern Med 1969; 70:833.
- Hermans C, Altisent C, Batorova A, et al. Replacement therapy for invasive procedures in patients with haemophilia: literature review, European survey and recommendations. Haemophilia 2009; 15:639.
- Martinowitz U, Varon D, Jonas P, et al. Circumcision in hemophilia: the use of fibrin glue for local hemostasis. J Urol 1992; 148:855.
- Kearney S, Sharathkumar A, Rodriguez V, et al. Neonatal circumcision in severe haemophilia: a survey of paediatric haematologists at United States Hemophilia Treatment Centers. Haemophilia 2015; 21:52.
- Anderson JA, Brewer A, Creagh D, et al. Guidance on the dental management of patients with haemophilia and congenital bleeding disorders. Br Dent J 2013; 215:497.
- Djulbegovic B, Marasa M, Pesto A, et al. Safety and efficacy of purified factor IX concentrate and antifibrinolytic agents for dental extractions in hemophilia B. Am J Hematol 1996; 51:168.
- Kempton CL, White GC 2nd. How we treat a hemophilia A patient with a factor VIII inhibitor. Blood 2009; 113:11.
- Mauser-Bunschoten EP, Zijl JA, Mali W, et al. Successful treatment of severe bleeding in hemophilic target joints by selective angiographic embolization. Blood 2005; 105:2654.
- Lusher JM. Use of prothrombin complex concentrates in management of bleeding in hemophiliacs with inhibitors--benefits and limitations. Semin Hematol 1994; 31:49.
- Astermark J, Donfield SM, DiMichele DM, et al. A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study. Blood 2007; 109:546.
- Young G, Shafer FE, Rojas P, Seremetis S. Single 270 microg kg(-1)-dose rFVIIa vs. standard 90 microg kg(-1)-dose rFVIIa and APCC for home treatment of joint bleeds in haemophilia patients with inhibitors: a randomized comparison. Haemophilia 2008; 14:287.
- Santagostino E, Mancuso ME, Rocino A, et al. A prospective randomized trial of high and standard dosages of recombinant factor VIIa for treatment of hemarthroses in hemophiliacs with inhibitors. J Thromb Haemost 2006; 4:367.
- Kavakli K, Makris M, Zulfikar B, et al. Home treatment of haemarthroses using a single dose regimen of recombinant activated factor VII in patients with haemophilia and inhibitors. A multi-centre, randomised, double-blind, cross-over trial. Thromb Haemost 2006; 95:600.
- Schneiderman J, Rubin E, Nugent DJ, Young G. Sequential therapy with activated prothrombin complex concentrates and recombinant FVIIa in patients with severe haemophilia and inhibitors: update of our previous experience. Haemophilia 2007; 13:244.
- Gringeri A, Fischer K, Karafoulidou A, et al. Sequential combined bypassing therapy is safe and effective in the treatment of unresponsive bleeding in adults and children with haemophilia and inhibitors. Haemophilia 2011; 17:630.
- Hay C, Lozier JN. Porcine factor VIII therapy in patients with factor VIII inhibitors. Adv Exp Med Biol 1995; 386:143.
- Hay CR, Lozier JN, Lee CA, et al. Safety profile of porcine factor VIII and its use as hospital and home-therapy for patients with haemophilia-A and inhibitors: the results of an international survey. Thromb Haemost 1996; 75:25.
- Brettler DB, Forsberg AD, Levine PH, et al. The use of porcine factor VIII concentrate (Hyate:C) in the treatment of patients with inhibitor antibodies to factor VIII. A multicenter US experience. Arch Intern Med 1989; 149:1381.
- Noble S, Chitnis J. Case report: use of topical tranexamic acid to stop localised bleeding. Emerg Med J 2013; 30:509.
- Stajcić Z. The combined local/systemic use of antifibrinolytics in hemophiliacs undergoing dental extractions. Int J Oral Surg 1985; 14:339.
- Hemophilia and von Willebrand's disease: 2. Management. Association of Hemophilia Clinic Directors of Canada. CMAJ 1995; 153:147.
- Revel-Vilk S, Blanchette VS, Sparling C, et al. DDAVP challenge tests in boys with mild/moderate haemophilia A. Br J Haematol 2002; 117:947.
- Rose EH, Aledort LM. Nasal spray desmopressin (DDAVP) for mild hemophilia A and von Willebrand disease. Ann Intern Med 1991; 114:563.
- Nolan B, White B, Smith J, et al. Desmopressin: therapeutic limitations in children and adults with inherited coagulation disorders. Br J Haematol 2000; 109:865.
- Mannucci PM, Ruggeri ZM, Pareti FI, Capitanio A. 1-Deamino-8-d-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands' diseases. Lancet 1977; 1:869.
- Dunn AL, Powers JR, Ribeiro MJ, et al. Adverse events during use of intranasal desmopressin acetate for haemophilia A and von Willebrand disease: a case report and review of 40 patients. Haemophilia 2000; 6:11.
- ACUTE THERAPY FOR BLEEDING
- Serious, life-threatening bleeding and head trauma
- - Initial considerations for severe bleeding
- - Factor dosing for severe bleeding
- - Considerations for hemarthroses
- - Factor dosing for joint bleeds
- Muscle/Soft tissue bleeding
- Minor bleeding
- URGENT/EMERGENT SURGERY
- ELECTIVE SURGERY
- Overview of surgical planning
- Major surgery
- Dental procedures
- Endoscopy or tonsillectomy
- SPECIAL POPULATIONS
- - Overview of patient with an inhibitor
- - Bypassing products (rFVIIa or FEIBA)
- - Recombinant porcine factor VIII (hemophilia A)
- - Plasmapheresis
- - High-dose factor infusion
- Patients receiving longer-lasting factor
- Patient with mild hemophilia
- Resource-poor settings (no access to purified factor)
- THERAPIES OTHER THAN FACTOR REPLACEMENT
- Antifibrinolytic therapy for mucosal bleeding
- Adjunctive local therapies
- DDAVP for mild hemophilia A
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS