组织因子阳性的细胞和微粒在胃癌高凝状态中的作用

目的:探讨胃癌患者血浆中组织因子阳性的血小板、白细胞和微粒的数量及其促凝活性。方法:将45例胃癌患者根据TNM分期分为Ⅰ、Ⅱ、Ⅲ、Ⅳ期,同时选取30例健康人作为对照组。采用流式细胞术检测组织因子阳性的细胞和微粒数。凝血酶生成实验检测细胞和微粒的凝血活性。结果:胃癌Ⅲ/Ⅳ期患者血浆中组织因子阳性的血小板、中性粒细胞、单核细胞和微粒的数量明显高于胃癌Ⅰ/Ⅱ期和健康对照组。胃癌Ⅲ/Ⅳ期患者血小板、白细胞和微粒的促凝活性与其他组相比显著升高,与增加凝血酶的生成速度和生成总量有关。用抗组织因子抗体抑制TF后,细胞和微粒的凝血活性明显下降。然而,使用抗膜连蛋白V抑制PS后,细胞和微粒的凝血活性虽然有下降趋势,但是并不明显。此外,根治性手术治疗可以降低组织因子阳性的血小板、中性粒细胞、单核细胞和微粒的数量。结论:组织阳性的血小板、中性粒细胞、单核细胞和微粒是胃癌Ⅲ/Ⅳ患者高凝状态的原因之一,通过抑制TF和凝血酶的生成可能降低胃癌患者的血栓发生率。

Tissue Factor-exposing Cells and Microparticels induce Procoagulant Activity in Gastric Cancer

ABSTRACT Objective: This study was designed to evaluate whether exposed tissue factor (TF) on platelets, leukocyte and mi- croparticles were involved in the hypercoagulability of gastric cancer. Methods: Gastric cancer patients were divided into four groups based on tumor-node-metastasis (TNM) stage, defined as stage I (n=10), stage II (n=10), stage III (n=15) or stage IV (n=10), and com- pared with healthy controls (n=30). Flow cytometry was used to quantify the counts of tissue factor positive cells and microparticels. The procoagulant activity of cells and microparticles were tested by thrombin production assays. Results: Using flow cytometry, we found TF+ platelets, neutrophils, monocytes and microparticles were significantly higher in stage III/IV patiens than in stage I/II patients and healthy controls. Moreover, the TF+ blood cells cooperated with microparticels, contributing to the increased rate and levels of thrombin formation. In addition, blockade of exposed TF on cells and micrparticles with anti-TF antibody significantly inhibited the procoagulant activity. However, blockade of exposed PS with annexin V has little effect on the procoagulant activity. Meanwhile, we found that treat- ment with radical resection could reduce the number of TF+ platelets, neutrophils, monocytes and microparticles. Conclusion: Our results suggest that TF+ platelets, leukocyte and microparticles play procoagulant roles in patients with gastric cancer. Blockade of TF and inhib- ite the formation of thrombin maybe the therapeutic target to prevent coagulation in patients with stage III/IV gastric cancer.