Systematic Review of Pediatric Venous Thromboembolism Associated with Inferior Vena Cava (IVC) Anomalies

Background

Congenital anatomic anomalies, such as those of the inferior vena cava (IVC), are rare. However, they can lead to serious complications such as venous thromboembolism (VTE), causing significant morbidity in pediatric patients. Published data on the clinical factors leading to VTE in this population are scarce, and the appropriate therapeutic management is unclear. We aimed to characterize pediatric patients with VTE secondary to IVC anomalies via a systematic review, to better understand the cause, risk factors, and management.

Methods

A systematic search of MEDLINE, EMBASE and Scopus was completed from January 2020 to July 2024. MeSH terms included: IVC anomaly, agenesis, atresia, absence, hypoplasia, malformation, venous thromboembolism, deep vein thrombosis. Articles were eligible if they reported the development of VTE associated with IVC anomalies in pediatric patients (<21 years of age). Single case reports, narrative reviews, case series including <3 cases, studies not reporting on the development of VTE, and studies including patients >21 years of age with outcomes not reported by age group were excluded. Descriptive statistics were used to summarize data.

Results

A total of 504 abstracts were screened, 37 full-text articles were reviewed, and 14 met final inclusion criteria (all were retrospective cohort studies, mostly single-center). These studies reported a total of 49 pediatric patients with VTE associated with IVC anomalies. Median age was 17 years (Q1-Q3 of 15-18 years) and patients were predominantly male (74%). The most common symptoms at presentation were lower extremity pain or swelling. The majority of VTE events involved the iliofemoral veins (76%), with 43% of events including bilateral thrombosis. Terminology for IVC anomalies or affected segments was not unified and included terms such as atresia, agenesis, absence, interruption and hypoplasia. The most common IVC segments involved were the suprarenal or infrarenal IVC (59%). Thrombophilia evaluation was positive in 39% of patients (heterozygosity for Factor V Leiden was the most common), with precipitating risk factors including oral contraceptive use and immobility in 35%. Sixteen patients underwent thrombolysis (33%). All patients received anticoagulation with a vitamin K antagonist or direct oral anticoagulant; data on treatment dosing versus prophylactic dosing were not consistently available. Median follow up duration reported in those on chronic anticoagulation was 14 months (range, 3 weeks to 116 months). Among 14 patients who discontinued anticoagulation, 8 patients (57%) had a recurrent VTE event, at a median of 3.5 months (range, 2 weeks - 18 years) following cessation of anticoagulation. Post-thrombotic syndrome (PTS) was noted in 48% of patients with reported PTS outcomes.

Conclusion

This is the first systematic review of VTE in pediatric patients with IVC anomalies. Presentation was predominantly in adolescent males, with thrombophilia risk noted in 39%. Descriptions of those on chronic anticoagulation varied, although the reported recurrence rate of 57% in those who discontinued anticoagulation is substantial, emphasizing the need to consider chronic anticoagulation. A multicenter cohort study of pediatric patients with IVC anomalies may better identify characteristics of patients who are at greatest risk of developing VTE, and inform risks of VTE and bleeding in association with anticoagulation approaches for VTE treatment, primary prevention, and long-term secondary prevention.