Heparin regimens to prevent arterial thrombosis in children requiring heart catheterization

Children with heart defects since birth (that is, congenital heart disease) frequently undergo a particular type of invasive procedure termed cardiac catheterization, to help diagnose or correct their condition. This procedure consists of inserting a flexible plastic tube (catheter) into the blood vessels of the patient and guiding it to his or her heart, where a dye is injected before pictures of the heart are taken. Children undergoing this type of procedure may suffer unwanted complications in the arteries into which the catheter is inserted. It is estimated that approximately 1 out of 5 to 10 patients develop arterial blood clots (that is, thrombosis) and thus require additional treatment to prevent those clots from growing further.

Heparin, a medication known as a 'blood thinner' (that is, an anticoagulant drug), employed in clinical practice since 1935, has been used to decrease the number of arterial blood clots during heart catheterization. However, the best dose of heparin to be used in children during heart catheterization remains to be determined. This review included two small randomized controlled trials with a total of 492 participants. These two studies found only imprecise evidence that the risk of arterial clots was similar in both the low-dose and high-dose heparin groups. Only one study reported bleeding complications and the frequency of clots in veins, which were also not significantly different between groups. Side effects of heparin other than bleeding complications were not reported in either of the studies. However, because the two included studies were small and because of concerns about the quality of one of them due to the lack of information provided, their results are insufficient to determine the effects of different heparin doses. Further larger studies are required to answer this question.

Authors' conclusions: 

Due to the limitations of the current evidence, small number of included studies, and lack of details reported in one study, we are unable to determine the effects of different dosing regimens of unfractionated heparin for the prevention of vascular thrombosis during cardiac catheterization in children. A further adequately powered, randomized clinical trial is needed.

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Background: 

The role of cardiac catheterization in pediatrics has progressed significantly over the last two decades, evolving from a primary diagnostic tool to a primary treatment modality in children with congenital heart disease. Vascular complications, particularly arterial thrombosis, are among the most common unwanted post-cardiac catheterization events. In 1974, unfractionated heparin proved to be superior to placebo in decreasing the incidence of arterial thrombosis in pediatric patients. However, the optimal dose of unfractionated heparin to be utilized in this setting remains a matter of controversy.

Objectives: 

To evaluate the use of low-dose (< 100 units/kg) versus high-dose (≥ 100 units/kg) unfractionated heparin administered as an intravenous bolus at the time of initiation of cardiac catheterization (that is, immediately after arterial puncture), with or without subsequent heparin maintenance doses, for the prevention of post-procedural arterial thrombosis in children.

Search strategy: 

The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched November 2013) and CENTRAL (2013, Issue 10). The authors searched MEDLINE, EMBASE, and the Virtual Health Library. Clinical trials databases and sources of grey literature were searched. No language restrictions were applied.

Selection criteria: 

Randomized or quasi-randomized trials that compared low dose to high dose unfractionated heparin administered prior to cardiac catheterization were included. We selected studies conducted in children aged 0 to 18 years.

Data collection and analysis: 

The first screening of potentially eligible studies was conducted by one of the authors (MLA). The second screening, quality assessment and data extraction were independently conducted by two authors (MLA, LRB). Outcomes (thrombotic events, bleeding complications, other complications) were treated as dichotomous variables. The effect measures used were risk ratio (RR), risk difference (RD) and number needed to treat (NNT), with 95% confidence intervals (CI).

Main results: 

Two studies with a total of 492 participants were eligible for inclusion. Risk of bias was low for all domains in one of the studies and unclear for the other. One of the trials was stopped early. The quality of evidence for our key outcomes was moderate. The CI for the risk of arterial thrombotic events was compatible with benefits of either high or low unfractionated heparin dose regimens (RR low-dose versus high-dose 1.06, 95% CI 0.58 to 1.92). Only one of the studies reported the frequency of bleeding events for the cohort of patients and found no statistically significant difference in the incidence of major and minor bleeding events between arms (RR low-dose versus high-dose 1.38, 95% CI 0.46 to 4.13 for minor bleeding; RR low-dose versus high-dose 2.96, 95% CI 0.12 to 71.34 for major bleeding events). This study also reported on the incidence of deep vein thrombosis when comparing the high versus low dose of heparin and reported a non-significant difference (RR low-dose versus high-dose 0.34, 95% CI 0.01 to 8.28). The other study lacked information about bleeding. Side effects of heparin other than bleeding complications were not reported in either of the studies.

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