Acquired bleeding disorders
Autoimmune based inhibitors in nonhemophiliac patients

Author: Kendall Crookston, M.D., Ph.D., Lizabeth Rosenbaum, M.D. and Julie Gober-Wilcox, M.D. (see Authors page)

Revised: 2 March 2016, last major update June 2010

Copyright: (c) 2002-2016,, Inc.

PubMed Search: Autoimmune inhibitors
Cite this page: Autoimmune based inhibitors in nonhemophiliac patients. website. Accessed October 23rd, 2016.
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)