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低分子量肝素与普通肝素用于癌症患者围手术期的血栓预防

Low molecular weight heparin versus unfractionated heparin for perioperative thromboprophylaxis in patients with cancer.

作者信息

Akl Elie A, Kahale Lara, Sperati Francesca, Neumann Ignacio, Labedi Nawman, Terrenato Irene, Barba Maddalena, Sempos Elena V, Muti Paola, Cook Deborah, Schünemann Holger

机构信息

Department of Internal Medicine, American University of Beirut, Riad El Solh St, Beirut, Lebanon.

出版信息

Cochrane Database Syst Rev. 2014 Jun 26(6):CD009447. doi: 10.1002/14651858.CD009447.pub2.

DOI:10.1002/14651858.CD009447.pub2
PMID:24966161
Abstract

BACKGROUND

The choice of the appropriate perioperative thromboprophylaxis in patients with cancer depends on the relative benefits and harms of low molecular weight heparin (LMWH) and unfractionated heparin (UFH).

OBJECTIVES

To update a systematic review of the evidence for the relative efficacy and safety of LMWH and UFH for perioperative thromboprophylaxis in patients with cancer.

SEARCH METHODS

We performed a comprehensive search for trials of anticoagulation in patients with cancer including a February 2013 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE. We also handsearched conference proceedings, reviewed reference list of included studies, used the 'related citations' feature in PubMed, and searched clinicaltrials.gov for ongoing studies.

SELECTION CRITERIA

Randomized controlled trials (RCTs) that enrolled patients with cancer undergoing a surgical intervention and compared the effects of LMWH to UFH on mortality, deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding outcomes, or thrombocytopenia.

DATA COLLECTION AND ANALYSIS

Two review authors independently used a standardized form to extract in duplicate data on participants, interventions, outcomes of interest, and risk of bias. Where possible, we conducted meta-analyses using the random-effects model.

MAIN RESULTS

Of 9559 identified unique citations, we included 16 RCTs with 12,890 patients with cancer, all using preoperative prophylactic anticoagulation. We identified no new study with this update. The overall quality of evidence was moderate. The meta-analyses did not conclusively rule out either a beneficial or harmful effect of LMWH compared with UFH for the following outcomes: mortality (risk ratio (RR) 0.89; 95% confidence interval (CI) 0.74 to 1.08), PE (RR 0.73; 95% CI 0.34 to 1.54), symptomatic DVT (RR 0.50; 95% CI 0.20 to 1.28), asymptomatic DVT (RR 0.81; 95% CI 0.66 to 1.01),major bleeding (RR 0.85; 95% CI 0.52 to 1.37), and minor bleeding (RR 0.92; 95% CI 0.47 to 1.79). LMWH was associated with lower incidence of wound hematoma (RR 0.68; 95% CI 0.52 to 0.88) but higher volume of intraoperative transfusion (mean difference (MD) 74 mL; 95% CI 47 to 102). The meta-analyses found no statistically significant differences for any of the following outcomes: reoperation for bleeding (RR 0.72; 95% CI 0.06 to 8.48) , intraoperative blood loss (MD= -6mL; 95% CI -87 to 74), postoperative transfusion (MD= 79mL; 95% CI -54 to 211), postoperative drain volume (MD= 27mL; 95% CI -44 to 98), and thrombocytopenia (RR 1.33; 95% CI 0.59 to 3.00).

AUTHORS' CONCLUSIONS: We found no difference between perioperative thromboprophylaxis with LMWH versus UFH in their effects on mortality, thromboembolic outcomes, major bleeding, or minor bleeding in patients with cancer. Further trials are needed to evaluate the benefits and harms of different heparin thromboprophylaxis strategies in this population more thoroughly.

摘要

背景

癌症患者围手术期血栓预防措施的选择取决于低分子量肝素(LMWH)和普通肝素(UFH)的相对获益与危害。

目的

更新关于LMWH和UFH用于癌症患者围手术期血栓预防的相对疗效和安全性证据的系统评价。

检索方法

我们全面检索了癌症患者抗凝治疗的试验,包括2013年2月对以下数据库的电子检索:Cochrane对照试验中央注册库(CENTRAL)、MEDLINE和EMBASE。我们还手工检索了会议论文集,查阅了纳入研究的参考文献列表,利用PubMed中的“相关引文”功能,并在ClinicalTrials.gov上搜索正在进行的研究。

选择标准

纳入接受手术干预的癌症患者的随机对照试验(RCT),比较LMWH与UFH对死亡率、深静脉血栓形成(DVT)、肺栓塞(PE)、出血结局或血小板减少症的影响。

数据收集与分析

两位综述作者独立使用标准化表格重复提取关于参与者、干预措施、感兴趣的结局以及偏倚风险的数据。在可能的情况下,我们使用随机效应模型进行荟萃分析。

主要结果

在9559条识别出的独特引文中,我们纳入了16项RCT,共12890例癌症患者,均采用术前预防性抗凝治疗。此次更新未发现新的研究。证据的总体质量为中等。荟萃分析未明确排除LMWH与UFH相比在以下结局方面的有益或有害影响:死亡率(风险比(RR)0.89;95%置信区间(CI)0.74至1.08)、PE(RR 0.73;95% CI 0.34至1.54)、有症状DVT(RR 0.50;95% CI 0.20至1.28)、无症状DVT(RR 0.81;95% CI 0.66至1.01)、大出血(RR 0.85;95% CI 0.52至1.37)和小出血(RR 0.92;95% CI 0.47至1.79)。LMWH与伤口血肿发生率较低相关(RR 0.68;95% CI 0.52至0.88),但术中输血量较高(平均差(MD)74 mL;95% CI 47至102)。荟萃分析发现以下任何结局均无统计学显著差异:因出血再次手术(RR 0.72;95% CI 0.06至8.48)、术中失血量(MD = -6mL;95% CI -87至74)、术后输血量(MD = 79mL;95% CI -54至211)、术后引流量(MD = 27mL;95% CI -44至98)以及血小板减少症(RR 1.33;95% CI 0.59至3.00)。

作者结论

我们发现LMWH与UFH在癌症患者围手术期血栓预防中对死亡率、血栓栓塞结局、大出血或小出血的影响无差异。需要进一步的试验更全面地评估该人群中不同肝素血栓预防策略的获益与危害。

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