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胶质来源的循环微颗粒和组织因子在高级别神经胶质瘤中的表达:一种潜在的促血栓形成作用。

Circulating microparticles of glial origin and tissue factor bearing in high-grade glioma: a potential prothrombotic role.

机构信息

Department of Cardiologic, Thoracic and Vascular Sciences, via Giustiniani 2, Padua, Italy.

出版信息

Thromb Haemost. 2013 Aug;110(2):378-85. doi: 10.1160/TH12-12-0957. Epub 2013 Jun 27.

Abstract

Venous thromboembolism (VTE) may complicate the clinical course of glioblastoma multiforme (GBM). Circulating microparticles (MPs) have been associated with cancer-related VTE. Sixty-one consecutive patients with GBM undergoing gross-total (41) or subtotal (20) surgical resection followed by radio-chemotherapy were prospectively evaluated. MPs numbers according to cellular origin and the procoagulant activity of annexin V positive (AV+) MPs (MP-activity) were measured before surgery and then 1 week and 1, 4, and 7 months after surgery. Glial (GFAP+) and endothelial (CD62E+) derived MPs, AV+ and tissue factor-bearing (TF+) MPs were measured using flow cytometry. Baseline levels of GFAP+/TF-, TF+/GFAP-, and GFAP+/TF+ MPs were significantly higher in GBM patients than in healthy controls, and significantly increased at each time point after surgery; at 7 months, a further significant increase over the level found a week after surgery was only seen in the subtotally resected patients. The number AV+/CD62E- MPs increased in GBM patients and correlated with MP activity. TF+/GFAP- MPs numbers were significantly higher in 11 GBM patients who developed VTE than in those who did not (p 0.04). TF+/GFAP- MPs levels above the 90th percentile (calculated in GBM patients without VTE) were associated with a higher risk of VTE (RR 4.17, 95% CI 1.57-11.03). In conclusion, the numbers of glial-derived and/or TF-bearing MPs were high in GBM patients both before and even more after the neoplasm was treated, especially in patients with subtotal resection likely according to disease progression. A contribution of TF+/GFAP- MPs to the risk of VTE is suggested.

摘要

静脉血栓栓塞症(VTE)可能会使多形性胶质母细胞瘤(GBM)的临床病程复杂化。循环微颗粒(MPs)与癌症相关的 VTE 有关。61 例连续接受大体全切除(41 例)或次全切除(20 例)手术,随后接受放化疗的 GBM 患者前瞻性评估。在手术前、手术后 1 周、1 个月、4 个月和 7 个月时,根据细胞起源测量 MPs 数量,并测量 Annexin V 阳性(AV + )MPs 的促凝活性(MP-活性)。使用流式细胞术测量胶质(GFAP + )和内皮(CD62E + )衍生的 MPs、AV + 和组织因子(TF + )携带的 MPs。与健康对照组相比,GBM 患者的基线 GFAP + /TF-、TF + /GFAP-和 GFAP + /TF + MPs 水平显著升高,并且在手术后的每个时间点均显著增加;在 7 个月时,仅在次全切除患者中发现手术后 1 周的水平进一步增加。GBM 患者的 AV + /CD62E- MPs 数量增加,并与 MP 活性相关。在 11 例发生 VTE 的 GBM 患者中,TF + /GFAP- MPs 数量明显高于未发生 VTE 的患者(p 0.04)。TF + /GFAP- MPs 水平高于 90 百分位数(在无 VTE 的 GBM 患者中计算)与 VTE 风险增加相关(RR 4.17,95%CI 1.57-11.03)。总之,在 GBM 患者中,胶质衍生和/或 TF 携带的 MPs 数量在肿瘤治疗前后均较高,尤其是在疾病进展的次全切除患者中。TF + /GFAP- MPs 可能对 VTE 的风险有一定的影响。

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