Enhanced Procoagulant Activity on Blood Cells after Acute Ischemic Stroke.

Abstract

The role of phosphatidylserine (PS)-mediated procoagulant activity (PCA) in stroke remains unclear. To ascertain this role, early dynamic evolution of PS exposure on blood cells and released microparticles (MPs) and the corresponding PCA were evaluated in patients with acute ischemic stroke (AIS). Flow cytometry analyses revealed that initial levels of PS exposure on erythrocyte, platelet, and leukocyte were 2.40-, 1.36-, and 1.38-fold higher, respectively, in AIS than the risk factor-matched (RF) controls. Concomitantly, total PS+ MPs were increased in AIS (1949±483/μl) compared with the RF group (1674±387/μl; P=0.019) and healthy controls (1052±179/μl; P<0.001). Specifically, PS+ erythrocytes gradually increased within 1week. PS+ platelets and MPs peaked at 24h and declined at 7days, while PS+ leukocytes were markedly elevated at 24h. Further, PS exposure on blood cells and MPs in stroke resulted in shortened clotting time with an accompanying increase in FXa and thrombin formation significantly. Treatment with lactadherin, a PS antagonist, delayed the coagulation time by approximately 20% and blocked the generation of FXa and thrombin by about 50%. Furthermore, initial counts of PS+ platelets and platelet MPs significantly correlated with stroke severity. Thrombin generation promoted by platelets and MPs at 12h was significantly higher in patients with cardioembolism than in patients without. The thrombophilic susceptibility of AIS patients can be partly ascribed to PS exposure on blood cells and the release of MPs. Our studies identify PS exposure as a potentially novel therapeutic target in the treatment of AIS.