Acquired bleeding disorders

Autoimmune based inhibitors in nonhemophiliac patients

Last author update: 1 June 2010
Last staff update: 23 September 2020

Copyright: 2002-2022,, Inc.

PubMed Search: Autoimmune inhibitors

Kendall Crookston, M.D., Ph.D.
Julie Kim Harrington, M.D.
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Cite this page: Crookston K, Rosenbaum LS, Gober-Wilcox J. Autoimmune based inhibitors in nonhemophiliac patients. website. Accessed May 18th, 2022.
Definition / general
  • An acquired hemophilia that occurs after development of an autoantibody directed against a specific coagulation protein in patients with no prior coagulation defect
  • Incidence of 0.2 to 1.0 per million per year
  • Median age at presentation is 60 - 70 years and is seen equally in males and females
  • Associated with autoimmune disorders, solid tumors, hematologic malignancies, dermatologic disorders, inflammatory bowel disease, respiratory diseases, diabetes, acute hepatitis (B and C), severe drug reactions, post-childbirth
  • 50% occur in patients with no known medical problems
Clinical features
  • Most common inhibitor is anti-factor VIII (Semin Thromb Hemost 2009;35:760)
  • Mortality rate of 8 - 22% with severe bleeding in up to 90% of affected individuals
  • Patients present with soft tissue bleeding such as gastrointestinal, urinary tract or intramuscular (vs. intra-articular bleeding in hereditary hemophilia)
  • An acquired hemophilia should be suspected in patients with a new onset bleeding disorder accompanied by an isolated prolonged PTT (Curr Gerontol Geriatr Res 2010;2010:927503)
  • Patients should be referred to a hemophilia center with expertise in managing inhibitors (Haematologica 2009;94:566)
  • Poor prognostic factors are advanced age and lack of treatment (Semin Thromb Hemost 2009;35:769)
  • Prolonged PTT that does not correct with mixing studies
    • Note: PTT may initially be normal and then increases after 1 - 2 hours incubation
  • Normal PT
  • A nonlinear curve in a factor assay is often a clue to the presence of an inhibitor
  • The Bethesda assay is performed to detect and quantitate presence of inhibitor by diluting inhibitor patient plasma with pooled normal plasma
    • Each Bethesda unit of inhibitor indicates a decrease of factor VIII concentration in assay by 50% (1 unit → a reduction from 100% to 50%, 2 units → to 25%, 3 units → 12.5%, etc.)
  • Prothrombin complex concentrates, recombinant factor VIIa, DDAVP, factor VIII concentrates, immunosuppressive agents (BMC Res Notes 2010;3:161), plasmapheresis (variable success)
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