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Catheter-associated DVT does not warrant routine thrombophilia testing
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Routine thrombophilia testing should not be recommended for children with central venous catheter–associated deep vein thrombosis, according to the results of a systemic review and meta-analysis.
“In children, central venous catheter–associated deep vein thrombosis (CADVT) accounts for greater than 85% of DVT,” Edward Vincent S. Faustino, MD, MHS, associate professor of pediatrics and clinical care at Yale School of Medicine, and colleagues wrote. “The pathophysiology of pediatric CADVT is poorly understood. Without doubt, the central venous catheter itself, causing endothelial damage and obstruction to flow, is thought to be the most potent factor. However, not all children with central venous catheter develop CADVT.”
Edward Vincent S. Faustino
Faustino and colleagues sought to determine whether thrombophilia increased the risk for CADVT in pediatric patients, and to identify potential risk factors associated with the condition.
The researchers used relevant medical databases to identify 16 controlled cohort studies, with a cutoff date of September 2015. All studies included pediatric and young adult patients aged younger than 21 years with central venous catheter, who received systematic testing for thrombophilic traits.
A comprehensive bias assessment considered whether studies were at risk for publication, selection, performance, detection, attrition and reporting bias. The researchers considered the risk for bias unclear if available data were insufficient. Studies that included 75% or more eligible children were considered low risk for selection bias, and studies in which 95% or more enrolled children were assessed for CADVT were considered low risk for attrition bias.
The presence of CADVT at any time during the study period served as the primary outcome measure. The researchers considered the presence of one or more trait — defined as per the studies included, except that researchers also considered heterozygous and homozygous Factor V Leiden and prothrombin gene mutations together a positive trait — as the primary exposure of interest.
The selected studies included data from 1,279 children. Nine studies involved children with malignancies (n = 629) and two studies enrolled children with cardiac diseases (n = 230); the remaining studies included mixed diagnoses that could not be comprehensively categorized.
The studies used a total of 12 traits, with a median of six (range, 2-11) per study.
The researchers did not observe a significant publication bias in the included studies, but were unable to adequately assess the risks for selection and detection biases due to missing data.
In total, 237 children had one or more trait associated with thrombophilia (pooled prevalence, 0.2; 95% CI, 0.14-0.26).
The included studies exhibited a high rate of heterogeneity (I2 = 86.7%), and the prevalence of thrombophilia in each study correlated with the number of traits tested (P = .02). However, the year of publication did not appear associated with the prevalence of thrombophilia.
Traits most associated with thrombophilia included elevated Factor VIII (pooled prevalence, 0.11; 95% CI, 0.06-0.17) and elevated lipoprotein (pooled prevalence, 0.11; 95% CI, 0.04-0.2).
CADVT occurred in 277 children (pooled prevalence, 0.23; 95% CI, 0.15-0.34) and was associated with having one or more associated trait (pooled OR = 3.2; 95% CI, 1.56-6.54).
Traits most associated with CADVT included protein C deficiency (pooled OR = 6.83; 95% CI, 1.35-34.49), elevated Factor VIII (pooled OR = 3.29; 95% CI, 1.02-10.6) and Factor V Leiden mutation (pooled OR = 2.99; 95% CI, 1.14-7.83).
The researchers observed a stronger association with thrombophilia in children with symptomatic CADVT than those with asymptomatic CADVT (pooled OR, 6.71 vs. 2.14).
Children with CADVT and a malignancy also displayed an association with thrombophilia (pooled OR = 2.73; 95% CI, 1.14-6.56); however, this association did not extend to other diagnoses.
“Thrombophilia confers additional risk [for] CADVT in children with central venous catheter,” Faustino and colleagues wrote. “Protein C deficiency, elevated Factor VIII and Factor V Leiden mutation are associated with CADVT. Because of the low prevalence of each trait, relatively weak association with CADVT, and limitations in our estimates and the included studies, we cannot recommend routine testing for thrombophilias in children with CADVT.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.
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