Role in of primary VTE prophylaxis in pediatric patients in hospitalized and critically ill settings: A systematic review and meta-analysis

Abstract Venous thromboembolism (VTE) is a major cause of morbidity in hospitalized and critically ill children . Currently there is a lack of consensus on pharmacologic prophylaxis strategies in pediatric patients due to potential bleeding risk and uncertain benefit. This systematic review aims to evaluate the benefit of primary anticoagulant prophylaxis in hospitalized and critically ill pediatric patients. As part of the ASH ISTH guideline effort on anticoagulant prophylaxis for pediatric VTE prevention, we searched PubMed, Embase, and The Cochrane Central Register of Controlled Trials for relevant literature from inception till April 2025. Screening and extraction were done in duplicate. A study was included if it included any of the primary outcomes of interest and where the population of interest, hospitalized children or those in critical care units and had received a prophylactic dose of anticoagulation for primary prevention. We statistically combined estimates using RevMan web using the random effect model. Reviewers assessed the risk of bias using the Cochrane RoB2 tool for randomized controlled trials, and ROBINS-I tool for nonrandomized studies of intervention. Reviewers assessed the certainty of evidence using the GRADE approach. This systematic review addresses mortality, CVAD related DVT, bleeding, and VTE as outcomes in two population, intervention, comparison, outcomes (PICO) questions on VTE prophylaxis. Meta-analysis reported risk ratios or differences (95% confidence intervals), and absolute effects per 1,000 patients. After screening 13289 studies, we included 14 studies assessing the use of primary VTE prophylaxis in hospitalized pediatric patients and in critical care settings. For anticoagulant prophylaxis in hospitalized patients, one RCT and four NRSI's were included. The included RCT showed that prophylaxis was associated with a 2% lower risk for all-cause mortality (Risk Difference −0.02, 0.06-0.01) and a 1% lower risk for major bleeding (RD −0.01, 0.04-0.02). For VTE, results showed a 12% higher risk in patients receiving prophylaxis (RR 1.12, 0.50-2.52). For symptomatic VTE, patients showed a 2% higher risk in patients receiving prophylaxis RR 1.02 (0.21-4.93). For asymptomatic VTE, results showed 13 more events per 1,000 participants (95% CI 42 fewer to 156 more) in patients receiving prophylaxis. Certainty was low for all results due to concerns over risk of bias and imprecision. Across the assessed outcomes in NRSI's, anticoagulation prophylaxis showed no difference compared to no prophylaxis in hospitalized individuals for mortality (RD 0, −0.03-0.04) and VTE related mortality (RD 0, −0.02- 0.03). Prophylaxis was associated with a 4% higher risk of VTE (RD 0.04, −0.01- 0.08), 2% higher risk of symptomatic VTE (RR 1.02, 0.21-4.93), and 18% higher risk of bleeding (RR 1.18, 1.08-1.29). All very low certainty evidence due to risk of bias and imprecision concerns. For anticoagulant prophylaxis in critically ill children, one RCT and six NRSI's were included. The included RCT showed that the group who received prophylaxis had 2.22 times the risk of mortality when compared to the no prophylaxis group (RR 2.22, 0.47–10.42). CVAD-related symptomatic DVT were 87% less in the group receiving prophylaxis (RR 0.13, 0.02–0.96). Prophylaxis was associated with a 4% higher risk of clinically relevant bleeding (RD 0.04, −0.06-0.14). Certainty of evidence was very low due to risk of bias and imprecision concerns. Six NRSI's reported on VTE prophylaxis in pediatrics in critical care. Results showed a 29% higher risk of VTE (RR 1.29, 0.48–3.45), 3% higher risk of bleeding (RD 0.03, −0.04-0.11), 7% higher risk of major bleeding (RD 0.07, 0.00 to 0.14), 1% higher risk nonmajor bleeding (RD 0.01, −0.04-0.06), 81% higher risk of clinically relevant major and nonmajor bleed (RR 1.81, 0.43–7.56), and 43% higher risk of mortality(RR 1.43, 0.18–11.43) in patients receiving prophylaxis in critical care compared to those not receiving. All very low certainty evidence due to risk of bias and imprecision concerns. Anticoagulant prophylaxis in hospitalized and critically ill children showed no clear benefit for mortality or VTE prevention and was linked to potential increase in bleeding risk. While prophylaxis is used in some settings, evidence on its routine use in pediatric patients both in hospital and critical care settings is limited and favors not using prophylaxis.