Global coagulation assays in hemophilia A: A comparison to conventional assays

BACKGROUND: Global assays measure the interactions of coagulants, anticoagulants, and platelets on thrombin generation and may reflect the comprehensive coagulation potential in patients with hemophilia better than conventional assays. OBJECTIVES: The objectives of the current study were to investigate the value of global assays for measuring and monitoring the coagulation potential of patients with hemophilia A (HA). PATIENTS/METHODS: Rotational thromboelastometry, thrombin generation assay (TGA), and activated partial thromboplastin time (APTT) clot waveform analysis were investigated in a cohort of patients with severe, moderate, and mild HA and compared with conventional assays. RESULTS: The maximum velocity (MaxVel) parameter of modified thromboelastometry analysis, initiated by tissue factor and in the presence of corn trypsin inhibitor (CTI), had 92% sensitivity and 95% specificity for hemophilia diagnosis. The MaxVel also strongly correlated with factor VIII (FVIII) levels of patients with HA (r = .805, P < .0001). CTI improved the sensitivity of TGA, providing more accurate results. In particular, peak height parameter of platelet‐rich plasma samples with CTI had a sensitivity and specificity of 100% and 94%, respectively, in all patients with HA. APTT clot waveform analysis minimum value of first derivative (Min1) and minimum value of second derivative (Min2) parameters (representing speed and acceleration of clot formation, respectively) were sensitive and correlated more strongly with FVIII levels than APTT clotting times did (Min1: r = 0.786, P < 0.0001; Min2: r = 0.759, P < 0.0001; APTT: r = −0.513, P = 0.001). CONCLUSIONS: The sensitivity and specificity of the global assays was method dependent. Correlation between clinical end points and thrombin generation might also be valuable in the era of non–factor replacement therapy.