Haemophilia A displays phenotypic heterogeneity with respect to clinical severity. The aim of this study was to determine if
tissue factor (TF)-initiated
thrombin generation profiles in whole blood in the presence of
corn trypsin inhibitor (CTI) are predictive of
bleeding risk in
haemophilia A. We studied factor(F) VIII deficient individuals (11 mild, 4 moderate and 12 severe) with a well-characterized 5-year
bleeding history that included haemarthrosis, soft tissue haematoma and annual FVIII concentrate usage. This clinical information was used to generate a
bleeding score. The
bleeding scores (range 0-32) were separated into three groups (
bleeding score groupings: 0, 0 and < or = 9.6, >9.6), with the higher
bleeding tendency having a higher score. Whole blood collected by phlebotomy and contact pathway suppressed by 100 microg mL(-1) CTI was stimulated to react by the addition of 5 pM TF. Reactions were quenched at 20 min by inhibitors.
Thrombin generation, determined by
enzyme-linked
immunosorbent assay for
thrombin-
antithrombin was evaluated in terms of clot time (CT), maximum level (MaxL) and maximum rate (MaxR) and compared to the
bleeding score. Data are shown as the mean+/-SD. MaxL was significantly different (P < 0.001) between the groups: 504 +/- 114, 315 +/- 117 and 194 +/- 91 nM; with higher
thrombin concentrations in the groups with lower
bleeding scores. MaxR was higher in the groups with a lower
bleeding score; 97 +/- 51, 86 +/- 60 and 39 +/- 16 nM min(-1) (P = 0.09). No significant difference was detected in CT among the groups, 5.6 +/- 1.3, 4.7 +/- 0.7 and 5.6 +/- 1.3 min. Our empirical study in CTI-inhibited whole blood shows that the MaxL of
thrombin generation appears to correlate with the
bleeding phenotype of
haemophilia A.