Do Children With CVC-Related Thromboses Need Anticoagulation Treatment?

Results from a prospective study of children who were hospitalized in a pediatric intensive care unit (PICU) revealed that the incidence of central vein catheter (CVC)–related thrombosis was lower than previous reports, as was the incidence of acute and long-term complications. The study, published in Blood, challenges the notion that critically ill children with asymptomatic CVC-related thrombosis (CVC-RT) require anticoagulation treatment.

Investigators identified 189 children (median age = 1 year; range = 0-17 years) treated in the PICU at the Royal Children’s Hospital in Melbourne, Australia, over a period of 16 months. All participants had a CVC placed in the jugular or femoral veins that remained in situ for more than 24 hours. Children were ineligible for the study if they had had a CVC placed into the subclavian vein, if they had a previous CVC in the same blood vessel within the past three years, or if they had no planned follow-up at the institution.

An ultrasound of the site where the CVC was placed was performed during admission; two years after CVC placement, patients underwent another ultrasound and an assessment for post-thrombotic syndrome (PTS).

“This study is distinct from previous work as children identified to have asymptomatic CVC-RT were not treated (the clinical team [was] kept blinded) and the entire cohort was followed for two years to determine the natural history of asymptomatic thrombosis,” explained the authors, led by Sophie Jones, PhD, from Royal Children’s Hospital and The University of Melbourne, Australia. Ultrasound results were only unblinded if a child developed signs of CVC-RT within 24 hours.

Three-quarters of the enrolled children (75%) had an underlying diagnosis of congenital heart disease, and nearly 69 percent were admitted to the PICU following cardiac surgery. Most patients (83.1%) had an unfractionated heparin (UFH) infusion commenced within 12 hours of CVC insertion, at a mean continuous dose of 10.4 U/kg/hour.

A total of 146 patients had an ultrasound performed at baseline; ultrasounds were not performed on the remaining 43 children because of parent refusal, dressing that obstructed the view of the vessels, or early discharge.

The researchers found CVC-RT (asymptomatic or symptomatic) in 32 patients (21.9%) at admission to the PICU (TABLE 1). One patient had symptomatic CVC-RT at the time of first ultrasound, and another developed symptomatic CVC-RT four days after a negative ultrasound. Both patients were receiving prophylaxis with UFH.

All but one child had their ultrasound results blinded to the treating team.

A total of 120 children had a follow-up visit at two years; this excluded 14 patients (7.4%) who died during the two-year period. Four of these patients had asymptomatic CVC-RT on their admission ultrasound, but an independent review panel deemed that these deaths were unrelated to  thrombi identified on the blinded ultrasound.

Two years after CVC placement, a total of 16 children (13.3%) had a thrombus, including nine patients who had no evidence of thrombus on their admission ultrasounds (TABLE 1).

All but one child had their ultrasound results blinded to the treating team.

A total of 120 children had a follow-up visit at two years; this excluded 14 patients (7.4%) who died during the two-year period. Four of these patients had asymptomatic CVC-RT on their admission ultrasound, but an independent review panel deemed that these deaths were unrelated to  thrombi identified on the blinded ultrasound.

Two years after CVC placement, a total of 16 children (13.3%) had a thrombus, including nine patients who had no evidence of thrombus on their admission ultrasounds (TABLE 1).

One child who had an embolic stroke 22 days after CVC removal was receiving 15 U/kg/hour of UFH as thromboprophylaxis, again suggesting that thromboprophylaxis was ineffective in this population.

“Outcome data for children with and without thrombosis did not differ,” the authors concluded. “When compared with the known risks of anticoagulation in sick children, this would suggest that asymptomatic CVC-RT, even in critically unwell children, might not require specific treatment.”

The following risk factors were associated with a higher likelihood of acute CVC-RT during admission: cardiac arrest, continuous UFH >10 U/kg/hour, and a major or clinically relevant bleeding episode. At two-year follow-up, only having a CVC placed into the femoral vein was associated with an increased risk for residual CVC-RT (TABLE 2).

Among the 126 children who underwent PTS assessments, 13 (10.3%) had some degree of PTS, and two met the criteria for clinically significant PTS, according to scores on the Manco-Johnson Instrument (MJI) and the Modified Villalta (MV) Scale. The authors added that there were substantial differences between the scoring tools, noting the inconsistency in the classification, diagnosis, and reporting of PTS in children as a limitation of this analysis. Also, the inclusion of a predominantly young cohort, mostly with [congenital heart disease] as the primary diagnosis may limit the generalizability of the findings to other children with CVCs or those with critical illness.

“The study highlights the limitations of the MV and MJI tools and suggests that the tools may have differential value in different age groups of children,” the authors concluded. For children with multiple risk factors for CVC-RT (like femoral placement of CVC), the researchers recommend that future studies attempt to develop risk-stratification methods that might “provide a more rational approach to thromboprophylaxis in critically ill children.”

The authors report no conflicts of interest.


Reference

Jones S, Butt W, Monagle P, et al. The natural history of asymptomatic central venous catheter-related thrombosis in critically ill children. Blood. 2018 October 30. [Epub ahead of print]

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