Coagulation function and mechanisms in various clinical phenotypes of patients with acquired factor V inhibitors

J Thromb Haemost. 2014 Sep;12(9):1503-12. doi: 10.1111/jth.12660. Epub 2014 Jul 29.


Background: The clinical phenotype of individuals with acquired factor V (A-FV) inhibitors varies from asymptomatic (non-B group) to life-threatening bleeding (B group), but the mechanism(s) underlying this variation in hemorrhagic phenotype are poorly understood.

Objective: To investigate coagulation mechanistically in a range of patients with A-FV antibodies.

Methods and results: Ten cases of A-FV inhibitors in the non-B (n = 5) and B groups (n = 5) were studied. Thrombin generation assays in these plasmas revealed little thrombin generation, despite similar FV activity levels in both groups. However, prothrombin time-based clot waveform analysis revealed that the clot times were significantly prolonged and the maximum velocity and acceleration of coagulation were lower in the B group than in the non-B group, suggesting that this technique might be useful for predicting and monitoring hemorrhagic symptoms. A-FV inhibitors from the non-B group recognized predominantly the FV heavy chain, whereas those from the B group recognized the light chain. Purified anti-FV autoantibodies (autoAbs) from the B group inhibited FV binding to phospholipid by 60-90%, whereas there was little effect on this reaction in the non-B group. In addition, anti-FV autoAbs from the non-B group impaired the activated protein C (APC) cofactor activity of FV in FVIIIa inactivation mechanisms, and delayed APC-catalyzed cleavage of FVa at Arg306, but not at Arg506, indicating the presence of APC resistance in the non-B group.

Conclusions: The results suggest that the different hemorrhagic phenotypes in A-FV inhibitors depend on the specific epitope of anti-FV autoAbs, and appear to be associated with an imbalance of procoagulant and anticoagulant function.

Keywords: APC resistance; blood coagulation factor inhibitors; clinical laboratory techniques; factor V; hemostatic techniques.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants
  • Blood Coagulation Tests
  • Blood Coagulation*
  • Coagulants / chemistry
  • Epitopes / chemistry
  • Factor V / antagonists & inhibitors*
  • Factor V / chemistry*
  • Factor Va / chemistry
  • Female
  • Hemorrhage / diagnosis
  • Hemorrhage / immunology
  • Hemostasis / immunology
  • Humans
  • Male
  • Partial Thromboplastin Time
  • Phenotype
  • Protein Binding
  • Protein C / chemistry*
  • Prothrombin / chemistry
  • Prothrombin Time
  • Thromboplastin / chemistry
  • Thromboplastin / metabolism


  • Anticoagulants
  • Coagulants
  • Epitopes
  • Protein C
  • factor V clotting antigen
  • Factor Va
  • Factor V
  • Prothrombin
  • Thromboplastin