Contents

Search

coagulation factor VIII autoantibody (acquired hemophilia)

Etiology: 1) autoimmune diseases 2) postpartum state 3) hypersensitivity reactions to drugs 4) low-grade lymphocytic malignancy a) low-grade non-Hodgkin's lymphoma b) chronic lymphocytic leukemia 5) may occur in older patients without known underlying disorder Epidemiology: - postpartum: occurs most often after birth of 1st child Clinical manifestations: 1) massive subcutaneous or intramuscular bleeding 2) subdural hematoma [8] 2) postpartum a) commonly 1-3 month delay prior to onset of symptoms b) bleeding tendency, bleeding gums c) variable course Laboratory: - severely prolonged aPTT, NOT corrected with addition of normal plasma* - coagulation factor VIII inhibitor in plasma - prothrombin time is normal [8] * an incomplete correction consistent with autoantibody (from 95 to 45 seconds) [5] Differential diagnosis: - von Willebrand disease - family history, symptoms < 25 years - lesser prolongations of aPTT [8] although not expressed in numbers Management: 1) immunosuppressive therapy 2) acute bleeding a) recombinant factor VIIa concentrate - acts to bypass need for factor VIII by binding to surface of activated platelets, where it can generate factor Xa [1] - treatment of choice [1] b) prothrombin complex concentrate c) porcine factor VIII (generally less reactive with anti-human factor VIII) d) plasmapheresis 3) low titers of autoantibody (< 5 Bethesda units, without acute bleeding) may be treated with factor VIII concentrate or desmopressin [1] 4) immunosuppressive therapy - high-dose oral corticosteroids with cyclophosphamide 2 mg/kg/day or rituximab to eradicate inhibitor [1] 5) postpartum a) spontaneous resolution in most patients with 12-18 months of delivery b) recombinant factor VIIa [1] c) course shortened by immunosuppressive agents but not by corticosteroids alone

Interactions

drug adverse effects of antithrombotic agent(s)

Related

coagulation factor VIII alloantibody coagulation factor VIII inhibitor in plasma coagulation factor VIII; antihemophilic factor; AHF; procoagulant component; contains: factor VIIIa heavy chain, 200 kD & 92 isoforms; factor VIII B chain; factor VIIIa light chain (F8, F8C)

General

autoantibody coagulation factor VIII antibody

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2012, 2015. 2018, 2022.
  2. Schiller G, in: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  3. Barnett B, Kruse-Jarres R, Leissinger CA. Current management of acquired factor VIII inhibitors. Curr Opin Hematol. 2008 Sep;15(5):451-5. PMID: 18695367
  4. Gibson CJ, Berliner N, Miller AL et al A Bruising Loss. N Engl J Med 2016; 375:76-81. July 7, 201 PMID: 27406351 http://www.nejm.org/doi/full/10.1056/NEJMcps1500127
  5. Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
  6. Franchini M, Vaglio S, Marano G et al Acquired hemophilia A: a review of recent data and new therapeutic options. Hematology. 2017 Oct;22(9):514-520. Review. PMID: 28441921
  7. Kruse-Jarres R, Kempton CL, Baudo F er al Acquired hemophilia A: Updated review of evidence and treatment guidance. Am J Hematol. 2017 Jul;92(7):695-705. Review. PMID: 28470674 Free Article
  8. NEJM Knowledge+ Hematology