Low-dose warfarin for the prevention of central line-associated thromboses in children with malignancies - a randomized, controlled study

Background: Central venous lines ( CVLs) are essential in the care of children with malignancies, but are associated with venous thromboembolism ( VTE) and infections. Effective and safe prophylactic approaches are deficient. Aim: To perform a study of adjusted low-dose warfarin for the prevention of CVL-related VTE in children with malignancies. Methods: Children with newly diagnosed cancer, a CVL in a jugular vein and an expected treatment period of over 6 mo were eligible for the study. Participants were randomized to low-dose warfarin, with intended international normalized ratio ( INR) 1.3 - 1.9, or to a control group. Primary outcome was VTE in a jugular vein diagnosed by ultrasonography at 1, 3 and 6 mo after inclusion. Secondary outcome was CVL-related infections, mainly measured as days on antibiotics or positive blood cultures. Results: The study enrolled 73 children, and 62 completed it fully. Asymptomatic CVL-related VTE was frequent ( 42%), but often transient. Regardless of severity, timing and duration, CVL-related VTE was equally frequent among children on warfarin as compared to controls ( p = 0.44). Low-dose warfarin ( p = 0.59) or jugular CVL-related VTE ( p = 0.91) did not have any impact on days on antibiotics, but we observed a tendency towards an association between CVL-related VTE and positive blood cultures ( p = 0.15). Conclusion: Our randomized study of low-dose oral anticoagulation for the prevention of CVL-related asymptomatic VTE in children with cancer did not show any benefit of warfarin adjusted to maintain INR between 1.3 and 1.9.