Abstract
Patients with cancer-associated thrombosis (CAT) are commonly treated with low-molecular-weight heparin (LMWH), but whether dose capping is needed in patients over 90 kg is unclear. We conducted the WAVe study, a multicenter prospective cohort study in adult patients (≥ 18 years) with acute CAT and a weight of over 90 kg starting anticoagulation. Patients received weight-adjusted dalteparin at 200 IU/kg per day (up to 33 000 IU) for 30 (± 4) days, after which anticoagulation was continued per clinician discretion and followed for 6 months. The primary outcome was major bleeding (MB) at 30 days. Secondary outcomes included objectively confirmed recurrent venous thromboembolism (VTE) at 30 days and trough anti-Xa levels. The cumulative incidences of outcomes were estimated by time-to-event analysis, with death as a competing risk. The study stopped early due to recruitment challenges after 91 patients. Median weight and daily dose of dalteparin were 107.5 kg and 22 500 IU, respectively. Three patients had a MB episode for a cumulative incidence of 5.3% (95% CI 1.1%-14.8%) at 30 days. One patient had recurrent VTE for a cumulative incidence of 1.2% (95% CI 0.1%-5.7%) at 30 days. No significant bioaccumulation noted up to Day 30 based on trough anti-Xa levels. The median Day 7 trough anti-Xa levels were higher in those with bleeding events within 30 days compared to those without (0.6 vs. 0.2 IU/mL, p = 0.01). Our results suggest that weight-adjusted dosing of dalteparin in patients over 90 kg is associated with acceptable rates of bleeding and thrombosis. Trial Registration: NCT03297359.