Impact of Obesity and Overweight on Heparin Dosing and Clinical Outcomes in Pediatric Patients with Venous Thromboembolism.

Abstract

Dosing guidance for anticoagulation, the mainstay of venous thromboembolism (VTE) treatment, is lacking for obese children. We aimed to compare unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH) dosing requirements and clinical outcomes between obese/overweight and nonobese children.This monocentric retrospective cohort study included patients aged < 18 years old receiving anticoagulation for VTE. The outcomes were: (1) number of dose adjustments to reach therapeutic levels, (2) variation from initial dose, (3) thrombotic progression/recurrence, and (4) clinically relevant bleeding. Characteristics and dosing requirements of obese/overweight and nonobese children were compared using Pearson chi-square, Fisher exact, and Wilcoxon Mann-Whitney tests. Kaplan-Meier estimator compared the cumulative incidence of thrombotic recurrence/progression and clinically relevant bleeding between groups.We included 212 patients (median age: 6.2 years, 23.6% obese/overweight) having 258 anticoagulation encounters (LMWH: 82.6%, UFH: 17.4%). Most children had therapeutic levels following one dosage (66.7% in obese/overweight vs. 51.8% in nonobese, p = 0.201). Dosing requirements significantly differed between obese/overweight and nonobese children (average increase from initial dose: 3.2 vs. 11.3%, p < 0.001). In obese/overweight children, 11.1% of patients required ≥ 10% dose reduction versus 2.1% in nonobese children (p < 0.001). The cumulative incidence of thrombotic progression/recurrence was comparable between groups (obese/overweight: 12.0%, nonobese: 10.5%, p = 0.786). Similarly, clinically significant bleeding was rare for both groups (obese/overweight: 2.0%, nonobese: 3.1%, p = 0.609).In children treated for VTE, obesity/overweight was associated with lower anticoagulation requirements. Further prospective work is urgently needed to explore alternate regimens, such as dose capping, reduced initial dosing, or the use of fat-free mass.