Brandão Leonardo R, Shah Niketa, Shah Prakeshkumar S
Division of Haematology-Oncology, The Hospital for Sick Children, 555 University Avenue, Black Wing, room 10412, Toronto, Ontario, Canada, M5G-1X8.
Cochrane Database Syst Rev. 2014 Mar 10(3):CD005982. doi: 10.1002/14651858.CD005982.pub2.
The prevalence of children diagnosed with deep vein thrombosis or pulmonary embolism has been increasing in the last decade. The most common thrombosis risk factor in neonates, infants and children is the placement of a central venous catheter (CVC). To date, it is unknown if the practice of anticoagulation prophylaxis with low molecular weight heparin (LMWH) decreases CVC-related thrombosis in children.
The primary objective of this review was to determine the effect of LMWH prophylaxis on reducing the incidence of CVC-related thrombosis in children.Secondary objectives were to determine the effect of LMWH on occlusion of CVCs, number of days of CVC patency, episodes of catheter-related sepsis, side effects of LMWH (allergic reactions, major and minor bleeding complications, abnormal coagulation profile, osteoporosis) and mortality during therapy.
The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched June 2013), CENTRAL (2013, Issue 5) and clinical trial databases. The authors searched MEDLINE and EMBASE (July 2013). Bibliographies of identified articles were searched. There were no language restrictions.
Randomised and quasi-randomised trials comparing LMWH prophylaxis to standard care given to prevent CVC-related thrombotic events in children were included. We selected studies conducted in children aged 0 to 18 years.
Two review authors independently identified eligible studies, which were assessed for study quality including bias, and extracted unadjusted data where available. In the data analysis step, all outcomes were analysed as binary or dichotomous outcomes. The effects of interventions were summarised with risk ratios (RR) and their respective 95% confidence intervals (CI).
One of 17 studies retrieved for full-text assessment for eligibility was included in the final analysis. This study included a total of 186 participants and investigated the effect of LMWH to prevent CVC-related thrombosis compared to standard care. The risk of bias of the study was assessed to be low, except for the unclear risk of selection bias (allocation concealment not reported) and detection bias since it was an open-label study. Nonetheless, outcome adjudication was blinded. However, overall the quality of the evidence was low due to the fact that the study was underpowered. The CIs for the risk of CVC-related thrombosis (symptomatic and asymptomatic events) were compatible with benefits of either LMWH (reviparin) or the control (RR for symptomatic thrombosis 1.03, 95% CI 0.21 to 4.93; RR for asymptomatic thrombosis 1.17, 95% CI 0.45 to 3.08). Similarly, only one patient in the standard care group suffered a major bleeding event, while minor bleeding was found in 53.3% of patients in the reviparin arm and in 44.7% of patients in the standard care arm (major bleeding RR 0.34, 95% CI 0.01 to 8.26; minor bleeding RR 1.20, 95% CI 0.91 to 1.58). Lastly, there were two deaths within the study and neither were the result of a venous thrombotic event (VTE), occurring in the standard care arm. No additional adverse effects were reported. Other pre-specified outcomes for this review were not reported.
AUTHORS' CONCLUSIONS: A single study reported imprecise effects for the risk of CVC-related thrombosis in children on a CVC anticoagulant prophylaxis regimen. The quality of the evidence was low due to the fact that the included study was clearly underpowered, hampering any conclusions in regards to the efficacy of LMWH prophylaxis to prevent CVC-related thrombi in children. Further prospective randomised studies are highly encouraged.
在过去十年中,被诊断为深静脉血栓形成或肺栓塞的儿童患病率一直在上升。新生儿、婴儿和儿童中最常见的血栓形成危险因素是中心静脉导管(CVC)的置入。迄今为止,低分子量肝素(LMWH)抗凝预防措施是否能降低儿童CVC相关血栓形成尚不清楚。
本综述的主要目的是确定LMWH预防对降低儿童CVC相关血栓形成发生率的影响。次要目的是确定LMWH对CVC堵塞、CVC通畅天数、导管相关败血症发作、LMWH的副作用(过敏反应、严重和轻微出血并发症、凝血指标异常、骨质疏松)以及治疗期间死亡率的影响。
Cochrane外周血管疾病组试验搜索协调员检索了专业注册库(最后检索时间为2013年6月)、Cochrane系统评价数据库(2013年第5期)和临床试验数据库。作者检索了MEDLINE和EMBASE(2013年7月)。对已识别文章的参考文献进行了检索。没有语言限制。
纳入比较LMWH预防与预防儿童CVC相关血栓形成的标准治疗的随机和半随机试验。我们选择了在0至18岁儿童中进行的研究。
两位综述作者独立识别符合条件的研究,评估研究质量,包括偏倚,并在可行时提取未调整的数据。在数据分析步骤中,所有结局均作为二分类或二分法结局进行分析。干预措施的效果用风险比(RR)及其各自的95%置信区间(CI)进行总结。
在检索到的17项进行全文评估以确定是否符合纳入标准的研究中,有1项被纳入最终分析。该研究共纳入186名参与者,研究了与标准治疗相比,LMWH预防CVC相关血栓形成的效果。除了选择偏倚风险不明确(未报告分配隐藏情况)和检测偏倚(因为这是一项开放标签研究)外,该研究的偏倚风险被评估为低。尽管如此,结局判定是盲法的。然而,由于该研究样本量不足,总体证据质量较低。CVC相关血栓形成风险(有症状和无症状事件)的CI与LMWH(瑞肝素)或对照组获益情况相符(有症状血栓形成的RR为(1.03),95%CI为(0.21)至(4.93);无症状血栓形成的RR为(1.17),95%CI为(0.45)至(3.08))。同样,标准治疗组仅有1例患者发生严重出血事件,而瑞肝素组53.3%的患者和标准治疗组44.7%的患者出现轻微出血(严重出血RR为(0.34),95%CI为(0.01)至(8.26);轻微出血RR为(1.20),95%CI为(0.91)至(1.58))。最后,研究中有2例死亡,均不是静脉血栓形成事件(VTE)的结果,发生在标准治疗组。未报告其他不良反应。本综述的其他预先指定的结局未报告。
一项研究报告了儿童CVC抗凝预防方案中CVC相关血栓形成风险的效果不精确性。由于纳入的研究样本量明显不足,证据质量较低,阻碍了就LMWH预防儿童CVC相关血栓形成的疗效得出任何结论。强烈鼓励进一步开展前瞻性随机研究。