title: Coagulation function and mechanisms in various clinical phenotypes of patients with acquired factor V inhibitors.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Pediatrics, Nara Medical University, Kashihara, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Nogami
authors.forename: M
authors.initials: M
authors.lastname: Shima
mesh_terms: D000925:Anticoagulants; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D003029:Coagulants / Q000737:chemistry; D000939:Epitopes / Q000737:chemistry; D005165:Factor V / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D015943:Factor Va / Q000737:chemistry; D005260:Female; D006470:Hemorrhage / Q000175:diagnosis / Q000276:immunology; D006487:Hemostasis / Q000276:immunology; D006801:Humans; D008297:Male; D010314:Partial Thromboplastin Time; D010641:Phenotype; D011485:Protein Binding; D011486:Protein C / Q000737:chemistry*; D011516:Prothrombin / Q000737:chemistry; D011517:Prothrombin Time; D013925:Thromboplastin / Q000737:chemistry / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D003029:Coagulants; D000939:Epitopes; D011486:Protein C; C035876:factor V clotting antigen; D015943:Factor Va; D005165:Factor V; D011516:Prothrombin; D013925:Thromboplastin
keywords: APC resistance; blood coagulation factor inhibitors; clinical laboratory techniques; factor V; hemostatic techniques