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Coagulation function and mechanisms in various clinical phenotypes of patients with acquired factor V inhibitors
Author(s) -
Matsumoto T.,
Nogami K.,
Shima M.
Publication year - 2014
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12660
Subject(s) - group b , group a , thrombin , coagulation , factor v , phenotype , autoantibody , epitope , antibody , protein c , immunology , microbiology and biotechnology , chemistry , medicine , biology , platelet , biochemistry , thrombosis , gene
Summary 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 FVIII a inactivation mechanisms, and delayed APC ‐catalyzed cleavage of FV a 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.