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Coagulation

Acquired bleeding disorders

Factor V inhibitor


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: 17 August 2010, last major update August 2010
Copyright: (c) 2002-2010, PathologyOutlines.com, Inc.

Definition
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● An acquired alloantibody that develops against factor V that promotes either its increased clearance from the circulation or interference with its coagulation function
● Most are polyclonal IgG (which may also be associated with IgM or IgA)
● May behave like factor VIII inhibitor in mixing studies, with increasing PTT or PT after 1-2 hours

Epidemiology
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● 20% of cases are idiopathic
● In one study, 42% of cardiac surgery patients and 20% of neurosurgery patients developed factor V inhibitors after bovine thrombin exposure (Transfusion 2002;42:18)

Sites
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● Mucocutaneous and surgical site bleeding are the most common
● Hematuria, gastrointestinal bleeding, intracranial bleeding and hemospermia have also been observed

Etiology
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● Most cases of acquired factor V inhibitors are iatrogenic and are caused by exposure to bovine protein (i.e. bovine thrombin preparations)
● Antibodies are generated as an immune response to bovine factor V which then cross-reacts with endogenous factor V
● Other risk factors associated with factor V inhibitor development include recent surgery, drug exposure (e.g. aminoglycosides, B-lactam antibiotics), infections, blood transfusions, autoimmune disorders, malignancy and pregnancy

Clinical features
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● Highly variable
● Bleeding is typically severe and frequently fatal, however, in some instances there may be little to no bleeding
● Inhibitors usually manifest 7-10 days postoperatively and then disappear within 8 to 10 weeks; non-iatrogenic inhibitors may persist for significantly longer periods
● The titer of the inhibitor correlates with clinical severity
● Bovine thrombin associated factor V inhibitors are often accompanied by antibodies to other coagulation proteins such as fibrinogen, prothrombin and thrombin

Laboratory
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● Prolongation of PT and PTT with failure to correct with mixing studies
● A nonlinear curve in a factor assay is often a clue to the presence of an inhibitor
● Thrombin times may be prolonged if thrombin inhibitor is also present
● The Bethesda assay is performed to detect and quantitate the presence of inhibitor by diluting inhibitor patient plasma with pooled normal plasma
● Each Bethesda unit indicates a decrease of factor V concentration in the assay by 50% (1 unit: reduction from 100% to 50%; 2 units: to 25%; 3 units: to 12.5%, etc.)
● The Nijmegen assay is also used (Thromb Haemost 1995;73:247)

Prognostic factors
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● Non-iatrogenic inhibitors are associated with more severe bleeding and fatal outcomes

Case reports
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● Factor V inhibitor associated with cold agglutinin disease (Ann Hematol 1998;76:49)

Treatment
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● Steroids, cyclophosphamide, cyclosporine A, IV immunoglobulin
● Management of acute bleeding includes plasmapheresis, platelet transfusions and immunoabsorption

Differential diagnosis
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● May behave like factor VIII inhibitor in mixing studies, with increasing PTT or PT after 1-2 hours
● Combined factor V-factor VIII deficiency

Additional references
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Clin Appl Thromb Hemost 2006;12:485

End of Coagulation > Acquired bleeding disorders > Factor V inhibitor


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