[Development of Comprehensive Coagulation Assays Reflecting the Clinical Phenotype].

Abstract

PT, APTT, and coagulation factor activity are measured with clotting time-based methods. When coagula- tion and fibrinolysis are enhanced, TAT and PIC are detected, but evaluations of their hypofunctional state are difficult. We devised a new method that can be used to comprehensively and continuously evaluate coagula- tion and fibrinolysis in real time. We elucidated the clinical phenotype of congenital and acquired coagulation disorders using the following methods; (1) Clot waveform analysis (CWA) to evaluate fibrin formation; (2) Thrombin generation test (TGT) to monitor one-step before fibrin formation. (3) Thrombin/Plasmin generation assay (T/P-G) to evaluate fibrinolysis simultaneously with TGT. The results revealed that (1) CWA enabled the measurement of a very low FVIII activity level (FVIII:C 0.2-1.0 IU/dL) and detected a markedly severe type with FVIII:C <0.2 IU/dL. (2) For TGT, acquired hemophilia A showed a much lower value than that of congenital severe hemophilia A, being consistent with its severe bleeding. (3) CWA parameters for acquired factor V inhibitors in patients with bleeding symptoms were more impaired than with non-bleeding. Taken together these comprehensive assays can reflect the clinical phenotype and make it possible to analyze unidentified coagulation/fibrinolysis abnormality.