Coagulation
Acquired bleeding disorders
Factor V inhibitor

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 August 2010

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

PubMed Search: Factor V inhibitor [title]
Definition / General
  • 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
  • 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
  • Mucocutaneous and surgical site bleeding are the most common
  • Hematuria, gastrointestinal bleeding, intracranial bleeding and hemospermia have also been observed
Etiology
  • 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
  • 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
  • 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
  • Non-iatrogenic inhibitors are associated with more severe bleeding and fatal outcomes
Case Reports
Treatment
  • Steroids, cyclophosphamide, cyclosporine A, IV immunoglobulin
  • Management of acute bleeding includes plasmapheresis, platelet transfusions and immunoabsorption
Differential Diagnosis
  • May behave like factor VIII inhibitor in mixing studies, with increasing PTT or PT after 1 - 2 hours
  • Combined factor V-factor VIII deficiency