Falcione Sarina, Spronk Elena, Munsterman Danielle, Joy Twinkle, Boghozian Roobina, Jickling Glen C
Department of Medicine, Division of Neurology, University of Alberta, 11315 87th Ave NW, Edmonton, T6G 2H5, Canada.
Transl Stroke Res. 2025 Apr;16(2):169-177. doi: 10.1007/s12975-023-01200-1. Epub 2023 Nov 21.
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.
中风存在性别差异，包括中风风险和预后的差异。凝血酶生成的差异可能导致了女性和男性之间的这种差异。为了对此进行研究，我们评估了急性缺血性中风患者中女性和男性凝血酶生成的性别差异以及与血细胞基因表达的关系。在97例急性缺血性中风患者中，通过凝血酶生成试验测量凝血酶生成。通过微阵列测量血细胞基因表达。确定了两性之间凝血酶生成的差异，并研究了其与血细胞基因表达的关系。通过功能途径分析对与凝血酶生成性别差异相关的基因进行了分析。女性和男性产生凝血酶的总体能力相似。女性产生的凝血酶峰值为468.8 nM（标准差91.6），与男性相当（479.3 nM；标准差90.8；p = 0.58）。女性和男性之间的滞后时间、达到凝血酶峰值的时间以及内源性凝血酶潜力也相似。虽然中风患者中女性和男性的总体凝血酶生成相当，但促进这种凝血酶生成的基因存在差异。凝血酶峰值高的女性促进血栓形成和血小板活化的基因增加。相反，凝血酶峰值高的男性参与血栓降解的基因减少。急性缺血性中风的女性和男性产生凝血酶的能力相似，然而，在如何实现这种凝血酶生成方面可能存在差异，女性的凝血酶信号传导和血小板活化增加，而男性的血栓降解减少。这表明女性和男性之间可能存在血栓形成的调节差异，这可能导致中风的性别差异。
