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肺局部切除术和依诺肝素预防术后血栓形成改善局限性原发性肺腺癌患者的血液高凝状态。

Lobectomy and postoperative thromboprophylaxis with enoxaparin improve blood hypercoagulability in patients with localized primary lung adenocarcinoma.

机构信息

Service Anesthésie - Réanimation Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique Hôpitaux de Paris, France; ER2UPMC, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, France.

出版信息

Thromb Res. 2013 Nov;132(5):584-91. doi: 10.1016/j.thromres.2013.07.005. Epub 2013 Aug 29.

DOI:10.1016/j.thromres.2013.07.005
PMID:24094602
Abstract

BACKGROUND

Patients with lung adenocarcinoma undergoing surgery are in high risk for VTE and receive routine post-operative thromboprophylaxis with LWMH.

AIM

We investigated markers of hypercoagulability in patients with primary localized adenocarcinoma and the modifications induced by lobectomy and postoperative administration of enoxaparin.

MATERIALS AND METHODS

Patients suffering from localised primary lung adenocarcinoma (n=15) scheduled for lobectomy were studied. The control group consisted of 15 healthy age and sex-matched individuals. Blood was collected before anaesthesia induction and after surgery, at several intervals until the 7th post-operative day. Samples were assessed for thrombin generation, phosphatidylserin expressing platelet derived microparticles expressing (Pd-MP/PS(+)), tissue factor activity (TFa), FVIIa and TFPI levels, procoagulant phospholipid dependent clotting time and anti-Xa activity.

RESULTS

At baseline, patients showed increased thrombin generation and Pd-MP/PS(+). After lobectomy thrombin generation significantly decreased. Administration of enoxaparin attenuated thrombin generation. In about 50% of samples collected post-operatively an increase of thrombin generation occurred despite the presence of the expected anti-Xa activity in plasma. At the 7th post-operative day, 3 out of 15 patients showed a significant increase of thrombin generation.

CONCLUSION

In patients with localized lung adenocarcinoma, hypercoagulability is characterized by high thrombin generation and increased concentration of Pd-MP/PS(+). Tumor mass resection is related with attenuation of thrombin generation, which is inhibited by postoperative thromboprophylaxis with enoxaparin. The response to enoxaparin is not predicted by the concentration of the anti-Xa activity in plasma. The assessment of thrombin generation during prophylaxis with enoxaparin allows to identify patients with high residual plasma hypercoagulability.

摘要

背景

接受手术的肺腺癌患者存在发生静脉血栓栓塞(VTE)的高风险,术后常规接受低分子肝素(LWMH)预防血栓形成。

目的

我们研究了原发性局限性肺腺癌患者的高凝状态标志物,以及肺叶切除术和术后依诺肝素给药引起的变化。

材料和方法

研究了 15 例接受肺叶切除术的局部原发性肺腺癌患者。对照组由 15 名年龄和性别匹配的健康个体组成。在麻醉诱导前和手术后,在第 7 天的几个时间点采集血液样本。评估凝血酶生成、表达磷酸丝氨酸的血小板衍生微粒(Pd-MP/PS(+))、组织因子活性(TFa)、FVIIa 和 TFPI 水平、促凝磷脂依赖性凝血时间和抗-Xa 活性。

结果

基线时,患者表现出凝血酶生成和 Pd-MP/PS(+)增加。肺叶切除术后凝血酶生成显著降低。依诺肝素给药减弱了凝血酶生成。尽管血浆中存在预期的抗-Xa 活性,但在术后采集的大约 50%的样本中,凝血酶生成增加。在第 7 天,15 例患者中有 3 例显示出显著增加的凝血酶生成。

结论

在局限性肺腺癌患者中,高凝状态的特征是高凝血酶生成和增加的 Pd-MP/PS(+)浓度。肿瘤质量切除与凝血酶生成的减弱相关,术后用依诺肝素进行血栓预防可抑制凝血酶生成。对依诺肝素的反应不能通过血浆中抗-Xa 活性的浓度来预测。在依诺肝素预防期间评估凝血酶生成可以识别出具有高残留血浆高凝状态的患者。

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