Sex differences in
stroke exist, including variation in
stroke risk and outcome. Differences in
thrombin generation may contribute to this variation between females and males. To examine this, we assessed sex differences in
thrombin generation between females and males with
acute ischemic stroke and the relationship to blood cell gene expression. In 97 patients with
acute ischemic stroke,
thrombin generation was measured by
thrombin generation assay. Blood cell gene expression was measured by microarray. Differences in
thrombin generation between sexes were identified and the relationship to blood cell gene expression examined. Genes associated with sex differences in
thrombin generation were analyzed by functional pathway analysis. Females and males had similar overall capacity to generate
thrombin. The peak
thrombin generated in females was 468.8 nM (SD 91.6), comparable to males (479.3nM;SD 90.8; p = 0.58). Lag time, time to peak
thrombin, and endogenous
thrombin potential were also similar between females and males. While overall
thrombin generation was comparable between females and males with
stroke, differences in genes that promote this
thrombin generation exist. Females with high peak
thrombin had an increase in genes that promote
thrombosis, and platelet activation. In contrast, males with high peak
thrombin had a decrease in genes involved in
thrombus degradation. Females and males with
acute ischemic stroke have similar capacity to generate
thrombin, however, differences may exist in how this
thrombin generation is achieved, with females having increased
thrombin signaling, and platelet activation, and males having decreased
thrombus degradation. This suggests regulatory differences in
thrombosis may exist between females and males that may contribute to sex differences in
stroke.