Coagulation
Acquired bleeding disorders
Autoimmune based inhibitors in nonhemophiliac patients
Topic Completed: 1 June 2010
Minor changes: 23 September 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: Autoimmune inhibitors
Table of Contents
Definition / general | Epidemiology | Etiology | Clinical features | Laboratory | Treatment | Additional referencesCite this page: Crookston K, Rosenbaum LS, Gober-Wilcox J. Autoimmune based inhibitors in nonhemophiliac patients. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/coagulationautoimmunenonhemophiliac.html. Accessed October 23rd, 2021.
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
Epidemiology
- 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
Etiology
- 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)
Laboratory
- 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.)
Treatment
- Prothrombin complex concentrates, recombinant factor VIIa, DDAVP, factor VIII concentrates, immunosuppressive agents (BMC Res Notes 2010;3:161), plasmapheresis (variable success)
Additional references
