Lü Cheng-fang, Yu Hong-juan, Hou Jin-xiao, Zhou Jin
Department of Hematology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Chin Med J (Engl). 2008 Sep 20;121(18):1775-80.
Cisplatin based chemotherapy is a well recognized risk factor for coagulation disorders and thrombosis. The pathophysiological mechanisms by which cisplatin promote thrombosis are not well understood.
Red blood cells (RBCs) were separated from peripheral blood of patients with breast cancer (n = 10) and healthy adults (n = 6) and treated with cisplatin. Coagulation time of RBCs was assessed by one step recalcification time and the productions of thrombin, intrinsic and extrinsic factor Xa were measured in the presence or absence of various concentrations of lactadherin. Exposed phosphatidylserine was stained with lactadherin and observed by confocal microscopy and flow cytometry.
Neither fresh RBCs nor RBCs treated without cisplatin had potent procoagulant activity. Cisplatin treatment increased procoagulant activity of RBCs in a cell number- and concentration-dependent manner. Exposed phosphatidylserine was stained with lactadherin and after cisplatin treatment, strong fluorescence was revealed by confocal microscopy. Lactadherin bound RBCs from patients with breast cancer increased from (1.9 +/- 0.5)% on control RBCs to (68.0 +/- 3.5)% on RBCs treated with 10 micromol/L cisplatin for 24 hours.
Cisplatin treatment increases procoagulant activity of RBCs, which have a strong association with exposure of phosphatidylserine. The increased procoagulant activity may contribute to the pathogenesis of thrombophilia during cisplatin based chemotherapy in breast cancer patients.
基于顺铂的化疗是凝血障碍和血栓形成的一个公认风险因素。顺铂促进血栓形成的病理生理机制尚不清楚。
从乳腺癌患者（n = 10）和健康成年人（n = 6）的外周血中分离红细胞（RBC），并用顺铂处理。通过一步复钙时间评估RBC的凝血时间，并在存在或不存在不同浓度乳黏素的情况下测量凝血酶、内源性和外源性因子Xa的产生。用乳黏素对暴露的磷脂酰丝氨酸进行染色，并通过共聚焦显微镜和流式细胞术观察。
新鲜RBC和顺铂未处理的RBC均无强大的促凝血活性。顺铂处理以细胞数量和浓度依赖性方式增加RBC的促凝血活性。用乳黏素对暴露的磷脂酰丝氨酸进行染色，顺铂处理后，共聚焦显微镜显示出强荧光。乳腺癌患者的乳黏素结合RBC从对照RBC上的（1.9±0.5）%增加到用10 μmol/L顺铂处理24小时的RBC上的（68.0±3.5）%。
顺铂处理增加RBC的促凝血活性，这与磷脂酰丝氨酸的暴露密切相关。增加的促凝血活性可能有助于乳腺癌患者基于顺铂化疗期间血栓形成倾向的发病机制。
