Division of Internal Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd University Hospital, SE-182 88, Stockholm, Sweden.
Department of Medical Sciences, Division of Cancer Pharmacology and Computational Medicine, Uppsala University, Uppsala, Sweden.
Transl Stroke Res. 2020 Aug;11(4):708-719. doi: 10.1007/s12975-019-00777-w. Epub 2020 Jan 25.
Platelet microvesicles (PMV) have previously been found elevated in acute ischemic stroke (IS) and could be biomarkers for risk of recurrence. PMV surface antigens such as P-selectin and phosphatidylserine (PS) reflect platelet activation and procoagulance. Tissue factor-positive microvesicles (TFMV) are considered procoagulant, in particular if co-expressing PS. We enumerated MV subpopulations with these surface antigens in a cohort of 211 patients with primarily non-cardioembolic IS or transient ischemic attack (TIA) and investigated their association with long-term outcome. MV concentrations were determined by flow cytometry in the acute and convalescent phase. Primary outcome was a composite of fatal and non-fatal recurrent IS or myocardial infarction. Secondary outcomes were recurrent IS and all-cause mortality. Outcome events were obtained from Swedish registers during a follow-up of 1100 patient years. Concentrations of PS-positive and PS-negative MV populations were elevated in patients compared with healthy controls in both the acute and convalescent phase. PSTFPMV displayed pronounced elevations, median fold change 77 in the acute phase (p < 0.0001) but were not associated with outcome, neither were PSP-selectinPMV. The only subpopulation positively associated with primary outcome was PSTFPMV, with adjusted hazard ratio of 1.86 (1.04-3.31, p = 0.036) by Cox regression. Unexpectedly, several MV subpopulations tended to be associated with reduced risk of poor long-term outcome. Our results suggest that PSTFPMV may be a promising marker for cerebral ischemia, and that the in vivo generation of PSMV after IS/TIA warrants further study. Future MV studies should ideally enumerate PS and PSMV subpopulations separately.
血小板微囊泡（PMV）先前在急性缺血性中风（IS）中被发现升高，并且可能是复发风险的生物标志物。PMV 表面抗原，如 P-选择素和磷脂酰丝氨酸（PS），反映了血小板的激活和促凝活性。组织因子阳性微囊泡（TFMV）被认为是促凝的，特别是如果同时表达 PS。我们在一个主要是非心源性 IS 或短暂性脑缺血发作（TIA）的 211 例患者队列中对这些表面抗原的 MV 亚群进行了计数，并研究了它们与长期预后的关系。MV 浓度通过流式细胞术在急性期和恢复期确定。主要结局是致命和非致命性复发性 IS 或心肌梗死的复合事件。次要结局是复发性 IS 和全因死亡率。在 1100 患者年的随访期间，通过瑞典登记处获得了结局事件。与健康对照组相比，患者在急性期和恢复期的 PS 阳性和 PS 阴性 MV 群体的浓度均升高。PSTFPMV 显示出明显的升高，急性期的中位数倍数变化为 77（p<0.0001），但与结局无关，PSP-选择素 PMV 也无关。唯一与主要结局呈正相关的亚群是 PSTFPMV，Cox 回归分析的调整后危险比为 1.86（1.04-3.31，p=0.036）。出乎意料的是，一些 MV 亚群与较差的长期预后风险降低有关。我们的研究结果表明，PSTFPMV 可能是脑缺血的一个有前途的标志物，IS/TIA 后 PSMV 的体内产生值得进一步研究。未来的 MV 研究最好单独计数 PS 和 PSMV 亚群。
