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Acquired inhibitors of coagulation

Steven Coutre, MD
Section Editor
Lawrence LK Leung, MD
Deputy Editor
Jennifer S Tirnauer, MD


Acquired inhibitors of coagulation are antibodies that either inhibit the activity or increase the clearance of a clotting factor. A common clinical manifestation in affected patients is a hemorrhagic diathesis. The natural history and management of these inhibitors are quite different from inhibition due to alloantibodies that occur in patients with various inherited bleeding disorders (eg, congenital deficiencies of factors VIII, IX, or XI) treated with factor replacement. Acquired coagulation inhibitors that lead to bleeding will be reviewed here. Inhibitors in patients with hemophilia and factor XI deficiency are discussed separately. (See "Factor VIII and factor IX inhibitors in patients with hemophilia" and "Factor XI deficiency", section on 'FXI inhibitors'.)

Some disorders may be associated with antibodies to a variety of clotting factors. In systemic lupus erythematosus, for example, antiphospholipid antibodies and antibodies directed against factors II, VIII, IX, XI, XII, and XIII have been described [1]. (See "Clinical manifestations of antiphospholipid syndrome" and "Hematologic manifestations of systemic lupus erythematosus", section on 'Autoantibodies'.)

Antiphospholipid antibodies represent a special problem; these antibodies prolong certain clotting assays, but typically result in thrombosis rather than bleeding. The pathogenesis, diagnosis, and treatment of conditions associated with antiphospholipid antibodies are discussed elsewhere in UpToDate. (See "Pathogenesis of antiphospholipid syndrome" and "Clinical manifestations of antiphospholipid syndrome" and "Treatment of antiphospholipid syndrome".)


The most common autoantibodies that affect clotting factor activity and lead to a bleeding disorder are directed against, and interfere with, the activity of factor VIII, a condition also called acquired hemophilia A [2-7]. Although there are no large series describing the immunoglobulin class of the factor VIII autoantibodies, most have been IgG antibodies that do not bind complement.

The reasons for the production of factor VIII autoantibodies in a particular individual are not clear, but may involve the presence of certain gene polymorphisms (eg, HLA, CTLA4) and/or autoreactive CD4+ T lymphocytes [8,9].

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Literature review current through: Nov 2017. | This topic last updated: Oct 23, 2017.
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