The Role of Clot Waveform Analysis and Related Parameters in the Diagnosis and Treatment of Hemophilia A.

BACKGROUND:  Hemophilia A (HA) is an inherited bleeding disorder caused by a deficiency or defect in factor VIII (FVIII).

METHODS:  We investigated the role of clot waveform analysis (CWA) of activated partial thromboplastin time in the diagnosis and therapeutic monitoring of HA. The changes in CWA parameters the maximum clotting velocity (|Min1|), maximum clotting acceleration (|Min2|), and maximum clotting deceleration (|Max2|) were detected among mild, moderate, and severe HA groups.

RESULTS:  As the severity of HA subtypes increased, the levels of |Min1|, |Min2|, and |Max2| progressively decreased ( p  < 0.05). Receiver operating characteristic curve analysis showed that |Max2| and |Min2| were more effective than |Min1| in distinguishing different types of HA patients, with higher diagnostic efficacy. The standard curves based on Actin FSL reagent for normal and low levels of FVIII:C-|Max2| were established, with R2 values of 0.98 and 0.99, respectively. These curves can be utilized for monitoring during replacement therapies involving full-length recombinant FVIII and B-domain-deleted FVIII. Thirty cases of HA patients utilized the FVIII-|Max2| standard curve to obtain individual pharmacokinetics characteristic parameters. The clearance, half-life (t1/2 ), time to FVIII:C of 1% above baseline (tt1%), and predicted dosage showed no statistically significant differences compared with one-stage assay ( p  > 0.05).

CONCLUSION:  CWA is an economical and practical tool, and its related parameters are associated with the severity of HA. It has promising clinical prospects in predicting FVIII:C levels and individualized treatment when HA patients undergo replacement therapy.