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Acquired hemophilia: a rare but life-threatening potential cause of bleeding in the intensive care unit

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Abstract

Objective

There are a number of potential etiologies of severe bleeding encountered in the intensive care unit. Although rare, acquired hemophilia is one such etiology that often presents with major bleeding requiring intensive care. Despite the introduction of effective treatments, the reported mortality rate of patients with acquired hemophilia ranges from 6 to 8% and is in part attributable to sequential delays in diagnosis and appropriate treatment. The purpose of this review is to familiarize the intensive care specialist with this underrecognized cause of bleeding, with an emphasis on diagnosis and treatment.

Methods

As the objective of this article was to provide a concise overview of the diagnosis and management of acquired hemophilia, a directed search of English-language literature was undertaken using the PubMed database, targeting such topics as the differential diagnosis of bleeding in the intensive care unit and the epidemiology, diagnosis, and treatment of acquired hemophilia. Clinical study findings pertaining to the efficacy of specific treatments for acquired hemophilia were summarized.

Results and conclusion

Recognition of acquired hemophilia presents a clinical challenge, given the rarity of this condition, a general lack of familiarity with acquired hemophilia, and the potential for confusion with other more common causes of bleeding in the intensive care unit. Nevertheless, there are sentinel clinical and laboratory findings that should raise suspicion of this diagnosis. The treatment of acquired hemophilia is a multi-step, physiologically focused process aimed at controlling both active and recurrent bleeding. Therefore, prompt diagnosis is central to prognosis. Consultation with a hematologist may facilitate efficient diagnosis and management.

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References

  1. Handin RI (2005) Inherited platelet disorders. Hematology Am Soc Hematol Educ Program 2005:396–402

  2. Hassan AA, Kroll MH (2005) Acquired disorders of platelet function. Hematology Am Soc Hematol Educ Program 2005:403–408

  3. Levi M, Opal SM (2006) Coagulation abnormalities in critically ill patients. Crit Care 10:222

    Article  PubMed  Google Scholar 

  4. Rice TW, Wheeler AP (2009) Coagulopathy in critically ill patients: part 1: platelet disorders. Chest 136:1622–1630

    Article  PubMed  Google Scholar 

  5. Thomas A, Chalmers E (2005) The neonate with hemophilia. In: Lee CA, Berntorp EE, Hoots WK (eds) Textbook of hemophilia, 1st edn. Blackwell Publ, Oxford, pp 125–130

    Chapter  Google Scholar 

  6. Ogura H, Gando S, Iba T, Eguchi Y, Ohtomo Y, Okamoto K, Koseki K, Mayumi T, Murata A, Ikeda T, Ishikura H, Ueyama M, Kushimoto S, Saitoh D, Endo S, Shimazaki S, Japanese Association for Acute Medicine Disseminated Intravascular Coagulation Study Group (2007) SIRS-associated coagulopathy and organ dysfunction in critically ill patients with thrombocytopenia. Shock 28:411–417

    Article  PubMed  Google Scholar 

  7. Baudo F, de Cataldo F (2008) Acquired hemophilia in the elderly. In: Balducci L, Ershler W, de Gaetano G (eds) Blood disorders in the elderly, 1st edn. Cambridge University Press, Cambridge, pp 387–405

    Google Scholar 

  8. Franchini M, Lippi G (2008) Acquired factor VIII inhibitors. Blood 112:250–255

    Article  PubMed  CAS  Google Scholar 

  9. Hay CRM, Negrier C, Ludlam CA (1997) The treatment of bleeding in acquired haemophilia with recombinant factor VIIa: a multicentre study. Thromb Haemost 78:1463–1467

    PubMed  CAS  Google Scholar 

  10. Morrison AE, Ludlam CA, Kessler C (1993) Use of porcine factor VIII in the treatment of patients with acquired hemophilia. Blood 81:1513–1520

    PubMed  CAS  Google Scholar 

  11. Zeitler H, Ulrich-Merzenich G, Goldmann G, Vidovic N, Brackmann H-H, Oldenburg J (2010) The relevance of the bleeding severity in the treatment of acquired haemophilia––an update of a single-centre experience with 67 patients. Haemophilia 16:95–101

    Article  PubMed  CAS  Google Scholar 

  12. Tufano A, Coppola A, Guida A, Cimino E, De Gregorio AM, Cerbone AM, Di Minno G (2010) Acquired haemophilia A in the elderly: case reports. Curr Gerontol Geriatr Res 2010:927503. doi:10.1155/2010/927503

    PubMed  Google Scholar 

  13. Franchini M, Gandini G, Di Paolantonio T, Mariani G (2005) Acquired hemophilia A: a concise review. Am J Hematol 80:55–63

    Article  PubMed  CAS  Google Scholar 

  14. Collins PW, Percy CL (2010) Advances in the understanding of acquired haemophilia A: implications for clinical practice. Br J Haematol 148:183–194

    Article  PubMed  Google Scholar 

  15. Huth-Kühne A, Baudo F, Collins P, Ingerslev J, Kessler CM, Levesque H, Mingot Castellano ME, Shima M, St-Louis J (2009) International recommendations on the diagnosis and treatment of patients with acquired hemophilia A. Haematologica 94:566–575

    Article  PubMed  Google Scholar 

  16. Delgado J, Jimenez-Yuste V, Hernandez-Navarro F, Villar A (2003) Acquired haemophilia: review and meta-analysis focused on therapy and prognostic factors. Br J Haematol 121:21–35

    Article  PubMed  CAS  Google Scholar 

  17. Collins P, Baudo F, Huth-Kühne A, Ingerslev J, Kessler CM, Castellano ME, Shima M, St-Louis J, Lévesque H (2010) Consensus recommendations for the diagnosis and treatment of acquired hemophilia A. BMC Res Notes 3:161

    Google Scholar 

  18. Harper M, Obolensky L, Roberts P, Mercer M (2007) A case report of acute upper and lower airway obstruction due to retropharyngeal haemorrhage secondary to acquired haemophilia A. Anaesthesia 62:627–630

    Article  PubMed  CAS  Google Scholar 

  19. Hendricks MV, Hendricks LK, Davis WB (2002) A 54-year-old woman with acute airway obstruction. Chest 122:348–351

    Article  PubMed  Google Scholar 

  20. Bonnaud I, Saudeau D, de Toffol B, Autret A (2003) Recurrence of spontaneous subdural haematoma revealing acquired haemophilia. Eur Neurol 49:253–254

    Article  PubMed  Google Scholar 

  21. Baudo F, Caimi T, de Cataldo F (2010) Diagnosis and treatment of acquired haemophilia. Haemophilia 16:102–106

    Article  PubMed  CAS  Google Scholar 

  22. Shapiro SS (1996) The lupus anticoagulant/antiphospholipid syndrome. Annu Rev Med 47:533–553

    Article  PubMed  CAS  Google Scholar 

  23. Wheeler AP, Rice TW (2010) Coagulopathy in critically ill patients: part 2: soluble clotting factors and hemostatic testing. Chest 137:185–194

    Article  PubMed  CAS  Google Scholar 

  24. Lusher JM (1996) Screening and diagnosis of coagulation disorders. Am J Obstet Gynecol 175:778–783

    Article  PubMed  CAS  Google Scholar 

  25. Collins PW (2003) Management of acquired haemophilia A–more questions than answers. Blood Coagul Fibrinolysis 14:S23–S27

    Article  PubMed  Google Scholar 

  26. Buczma A, Windyga J (2007) Acquired haemophilia (in Polish). Pol Arch Med Wewn 117:241–245

    PubMed  Google Scholar 

  27. Ma AD, Carrizosa D (2006) Acquired factor VIII inhibitors: pathophysiology and treatment. Hematology Am Soc Hematol Educ Program 2006:432–437

  28. Zeitler H, Ulrich-Merzenich G, Hess L, Konsek E, Unkrig C, Walger P, Vetter H, Brackmann H-H (2005) Treatment of acquired hemophilia by the Bonn-Malmö protocol: documentation of an in vivo immunomodulating concept. Blood 105:2287–2293

    Article  PubMed  CAS  Google Scholar 

  29. Siow BL, Nadarajah K, Jayaratnam FJ (1982) Acquired hemophilia. A case report. Singapore Med J 23:328–330

    PubMed  CAS  Google Scholar 

  30. Kaufmann JE, Oksche A, Wollheim CB, Günther G, Rosenthal W, Vischer UM (2000) Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP. J Clin Invest 106:107–116

    Article  PubMed  CAS  Google Scholar 

  31. Hoffman M, Monroe DM, Roberts HR (2002) Platelet-dependent action of high-dose factor VIIa. Blood 100:364–365

    Article  PubMed  CAS  Google Scholar 

  32. Novo Nordisk A/S (2010) NovoSeven RT Coagulation Factor VIIa (Recombinant) (package insert). Novo Nordisk A/S, Bagsvaerd, Denmark

  33. Sumner MJ, Geldziler BD, Pedersen M, Seremetis S (2007) Treatment of acquired haemophilia with recombinant activated FVII: a critical appraisal. Haemophilia 13:451–461

    Article  PubMed  CAS  Google Scholar 

  34. Levi M, Levy JH, Andersen HF, Truloff D (2010) Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med 363:1791–1800

    Article  PubMed  CAS  Google Scholar 

  35. Neufeld EJ, Kessler CM, Gill JC, Wilke CT, Cooper DL, investigators on behalf of the HTRS investigators (2011) Exposure and safety of higher doses of recombinant factor VIIa ≥ 250 μg kg−1 in individuals with congenital haemophilia complicated by alloantibody inhibitors: the Haemophilia and Thrombosis Research Society Registry experience (2004–2008). Haemophilia. doi:10.1111/j.1365-2516.2010.02483.x

  36. Baxter Healthcare Corporation (2005) FEIBA VH Anti-Inhibitor Coagulant Complex (package insert). Baxter Healthcare Corp, Westlake Village

  37. Baxter Healthcare Corporation (2010) FEIBA NF (Anti-Inhibitor Coagulant Complex), Nanofiltered and Vapor Heated (package insert). Baxter Healthcare Corp, Westlake Village

  38. Sallah S (2004) Treatment of acquired haemophilia with factor eight inhibitor bypassing activity. Haemophilia 10:169–173

    Article  PubMed  CAS  Google Scholar 

  39. Luu H, Ewenstein B (2004) FEIBAR safety profile in multiple modes of clinical and home-therapy application. Haemophilia 10[Suppl 2]:10–16

    Article  PubMed  CAS  Google Scholar 

  40. Astermark J, Donfield SM, DiMichele DM, Gringeri A, Gilbert SA, Waters J, Berntorp E, Group ftFS (2007) A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study. Blood 109:546–551

    Article  PubMed  CAS  Google Scholar 

  41. Kessler CM (2005) New perspectives in hemophilia treatment. Hematology Am Soc Hematol Educ Program 2005:429–435

  42. Berntorp E (2009) Differential response to bypassing agents complicates treatment in patients with haemophilia with inhibitors. Haemophilia 15:3–10

    Article  PubMed  CAS  Google Scholar 

  43. Schneiderman J, Nugent DJ, Young G (2004) Sequential therapy with activated prothrombin complex concentrate and recombinant factor VIIa in patients with severe haemophilia and inhibitors. Haemophilia 10:347–351

    Article  PubMed  CAS  Google Scholar 

  44. Schneiderman J, Rubin E, Nugent DJ, Young G (2007) Sequential therapy with activated prothrombin complex concentrates and recombinant FVIIa in patients with severe haemophilia and inhibitors: update of our previous experience. Haemophilia 13:244–248

    Article  PubMed  CAS  Google Scholar 

  45. Martinowitz U, Livnat T, Zivelin A, Kenet G (2009) Concomitant infusion of low doses of rFVIIa and FEIBA in haemophilia patient’s with inhibitors. Haemophilia 15:904–910

    Article  PubMed  CAS  Google Scholar 

  46. Kelesidis T, Raphael J, Blanchard E, Parameswaran R (2010) Acquired hemophilia as the cause of life-threatening hemorrhage in a 94-year-old man: a case report. J Med Case Rep 4:231

    Article  Google Scholar 

  47. Jy W, Gagliano-DeCesare T, Kett DH, Horstman LL, Jimenez JJ, Ruiz-Dayao Z, Santos ES, Ahn YS (2003) Life-threatening bleeding from refractory acquired FVIII inhibitor successfullly treated with rituximab. Acta Haematol 109:206–208

    Article  PubMed  Google Scholar 

  48. Guillet B, Kriaa F, Huysse MG, Proulle V, George C, Tchernia G, D’Oiron R, Laurian Y, Charpentier B, Lambert T, Dreyfus M (2001) Protein A sepharose immunoadsorption: immunological and haemostatic effects in two cases of acquired haemophilia. Br J Haematol 114:837–844

    Article  PubMed  CAS  Google Scholar 

  49. Green D, Rademaker AW, Briet E (1993) A prospective, randomized trial of prednisone and cyclophosphamide in the treatment of patients with factor VIII autoantibodies. Thromb Haemost 70:753–757

    PubMed  CAS  Google Scholar 

  50. Brack A, Vogeler S, Hilpert J, Berger G, Buhr HJ, Koscielny J (2009) Acquired factor VIII inhibitor. Anesthesiology 111:1151–1154

    Article  PubMed  Google Scholar 

  51. Huth-Kühne A, Lages P, Hampel H, Zimmermann R (2003) Management of severe hemorrhage and inhibitor elimination in acquired hemophilia: the modified Heidelberg–Malmo protocol. Haematologica 88:86–92

    Google Scholar 

  52. Nemes L, Pitlik E (2000) New protocol for immune tolerance induction in acquired hemophilia. Haematologica 85:64–68

    PubMed  CAS  Google Scholar 

  53. Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CRM (2007) Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors’ Organisation. Blood 109:1870–1877

    Article  PubMed  CAS  Google Scholar 

  54. Collins P, Budde U, Rand JH, Federici AB, Kessler CM (2008) Epidemiology and general guidelines of the management of acquired haemophilia and von Willebrand syndrome. Haemophilia 14:49–55

    Article  PubMed  Google Scholar 

  55. Levy JH, Dutton RP, Hemphill JC III, Shander A, Cooper D, Paidas MJ, Kessler CM, Holcomb JB, Lawson JH (2010) Multidisciplinary approach to the challenge of hemostasis. Anesth Analg 110:354–364

    Article  PubMed  Google Scholar 

  56. McGilvray ID, Rotstein OD (2001) Assessment of coagulation in surgical critical care patients. In: Holzheimer RG, Mannick JA (eds) Surgical treatment: evidence-based and problem-oriented. Zuckschwerdt, Munich

    Google Scholar 

  57. Neparidze N, Kriz N, Ornstein DL (2009) Hetastarch haemophilia. Haemophilia 15:976–979

    Article  PubMed  CAS  Google Scholar 

  58. Schöchl H, Nienaber U, Hofer G, Voelckel W, Jambor C, Scharbert G, Kozek-Langenecker S, Solomon C (2010) Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM)-guided administration of fibrinogen concentrate and prothrombin complex concentrate. Crit Care 14:R55

    Article  PubMed  Google Scholar 

  59. Tiede A, Priesack J, Werwitzke S, Bohlmann K, Oortwijn B, Lenting P, Eisert R, Ganser A, Budde U (2008) Diagnostic workup of patients with accquired von Willebrand syndrome: a retrospective single-centre cohort study. J Thromb Haemost 6:569–576

    Article  PubMed  CAS  Google Scholar 

  60. Seegmiller A, Sarode R (2008) Acquired bleeding disorders. In: Irwin RS, Rippe JM (eds) Irwin and Rippe’s intensive care medicine, 6th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1323–1334

    Google Scholar 

  61. Angstwurm MWA, Dempfle CE, Spannagl M (2006) New disseminated intravascular coagulation score: a useful tool to predict mortality in comparison with Acute Physiology and Chronic Health Evaluation II and Logistic Organ Dysfunction scores. Crit Care Med 34:314–320

    Article  PubMed  Google Scholar 

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Acknowledgments

Writing support was provided by Lara Primak, MD, of ETHOS Health Communications, Newtown, Pennsylvania, with financial assistance from Novo Nordisk, Inc., in compliance with international guidelines for Good Publication Practice.

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Authors and Affiliations

  1. Department of Anesthesiology and Critical Care Medicine, Englewood Hospital and Medical Center, 350 Engle Street, Englewood, NJ, 07631, USA

    Aryeh Shander

  2. Division of Hematology and Medical Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA

    Christopher E. Walsh & Caroline Cromwell

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  1. Aryeh Shander
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  2. Christopher E. Walsh
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Correspondence to Aryeh Shander.

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Shander, A., Walsh, C.E. & Cromwell, C. Acquired hemophilia: a rare but life-threatening potential cause of bleeding in the intensive care unit. Intensive Care Med 37, 1240–1249 (2011). https://doi.org/10.1007/s00134-011-2258-5

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