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Coagulation

Acquired bleeding disorders

Autoimmune based inhibitors in nonhemophiliac patients


Reviewers: Kendall Crookston, M.D., Ph.D., University of New Mexico; Lizabeth Rosenbaum, MD, University of New Mexico; Julie Gober-Wilcox, M.D., Resident, University of New Mexico (see Reviewers page)
Revised: 9 April 2013, last major update June 2010
Copyright: (c) 2002-2013, PathologyOutlines.com, Inc.

Definition
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● An acquired hemophilia that occurs after development of an autoantibody directed against a specific coagulation protein in patients with no prior coagulation defect

Epidemiology
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● 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
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● 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
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● 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
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● 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: to 12.5%, etc.)

Treatment
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● Prothrombin complex concentrates, recombinant factor VIIa, DDAVP, factor VIII concentrates, immunosuppressive agents (BMC Res Notes 2010;3:161), plasmapheresis (variable success)

Additional references
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Blood 2008;112:250, Arch Pathol Lab Med 2000;124:730

End of Coagulation > Acquired bleeding disorders > Autoimmune based inhibitors in nonhemophiliac patients


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