Blood thinners for the prevention of blood clots in children with central venous lines

Over the last 10 years, the number of children found to have blood clots in their blood vessels, called veins, has become more common. As blood clots can either block these vessels and change their normal blood flow or shower pieces into other veins placed in important organs, serious health problems including death can occur. Venous clots are usually found in children with plastic tubes placed inside their blood vessels, called central lines, which are inserted to help or save the patient's life. However, these lines can also cause blood clots. We do not know if giving a medication to protect against blood clots, called an anticoagulant or low molecular weight heparin (LMWH), would protect against the clots. Therefore, we looked at all the research in children with central lines who received, or not, LMWH and only found one study with a total of 186 participants. This study did not have enough participants to show if this medication protects children with central lines from getting blood clots. The study also did not show that children on LMWH, at the doses given, experience too much bleeding because of its use. The included study did not report any additional adverse events. There were two deaths within the study in the standard care arm, and neither were due to a blood clot. Future studies looking at the role of this medication (LMWH) and if it protects children with central venous lines from getting blood clots are needed.

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.

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Background: 

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.

Objectives: 

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.

Search strategy: 

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.

Selection criteria: 

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.

Data collection and analysis: 

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).

Main results: 

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.

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