New assays for monitoring haemophilia treatment

Abstract

Precise measurements of factor VIII (FVIII) or factor IX (FIX) activity are believed to be essential for clinical management in haemophilia, although discrepancies between factor levels and clinical severity have been recognized. Clot wave form analysis has demonstrated that different wave form patterns may be evident in severe haemophilia A patients with levels of FVIII activity <1 IU dL(-1), and this might explain, in part, the phenotypic heterogeneity seen in these patients. In addition, the relatively new technique of computer-assisted thrombelastography (TEG), in which coagulation is initiated by tissue factor, has revealed a considerable degree of variability in different patients in the presence FVIII levels, which are sufficient to normalize TEG parameters. In contrast, a global thrombin generation test (TGT) has been proposed as a sensitive and reliable method for assessing overall clotting function in haemophilia patients. Several studies have demonstrated a significant correlation between TGT and FVIII/FIX levels, and these measurements also appear to correlate with the clinical phenotype. The TGT may be very useful, therefore, for evaluating overall haemostasis in different clinical situations, although substantial inter-assay and inter-individual variations have been reported. Both the TEG and TGT have been found to be particularly helpful for monitoring haemostatic therapy with bypassing agents or conventional FVIII or FIX concentrates in patients with inhibitors. These global tests enable the selection of appropriate therapeutic agents in individual circumstances and offer the opportunity to tailor the most effective haemostatic treatment even during severe bleeding or major surgery.