Up-regulation of platelet activation in hemophilia A

BACKGROUND: Platelets are an underappreciated factor in the classification of the bleeding tendency of patients with hemophilia. In this cross-sectional study, we investigated platelet activation status and responsiveness in relation to residual factor VIII activity and, within the group with severe hemophilia (<1% residual factor VIII activity), to annual factor VIII consumption. DESIGN AND METHODS: Twenty-one patients with mild-moderate hemophilia A, 13 with severe hemophilia A and 21 healthy controls were studied. The basal level of platelet activation and platelet responsiveness to activation and inhibition were determined by the measurement of platelet P-selectin expression and soluble platelet activation markers. RESULTS: Patients with severe hemophilia A had a higher percentage of activated platelets at baseline (15.9%) when compared to patients with mild-moderate hemophilia A (8.2%, P=0.014) and controls (6.4%, P<0.001). Both patients with mild-moderate hemophilia A and those with severe hemophilia A had higher levels of the soluble platelet activation markers platelet factor 4 (1.4 and 1.8 pg/10(6) platelets), CXCL7 (65.8 and 48.2 pg/10(6) platelets) and RANTES (12.8 and 9.5 pg/10(6) platelets), compared to controls (platelet factor 4: 0.3 pg/10(6) platelets, P<0.001 and <0.001; CXCL7 20.0 pg/10(6) platelets, P<0.001 and <0.001; RANTES 4.5 pg/10(6) platelets, P<0.001 and =0.003, respectively). In support of these observations, we found clinical evidence that higher platelet P-selectin expression correlates with lower factor VIII consumption in patients with severe hemophilia (Spearman's r -0.65, P=0.043). CONCLUSIONS: This study indicates that platelets from patients with severe hemophilia A are in a pre-activated state and that this pre-activated state is associated with factor VIII consumption.