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.


OBJECTIVE
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).


CONCLUSIONS
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.
Ruud
Ellen
E
Department of Paediatrics, Rikshospitalet University Hospital, Oslo, Norway. ellen.ruud@rikshospitalet.no
Holmstrøm
Henrik
H
De Lange
Charlotte
C
Hogstad
Ellen M
EM
Wesenberg
Finn
F
D000925:Anticoagulants / Q000008:administration & dosage*; D002405:Catheterization, Central Venous / Q000009:adverse effects*; D002408:Catheters, Indwelling / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007601:Jugular Veins; D008297:Male; D009369:Neoplasms / Q000188:drug therapy; D020246:Venous Thrombosis / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage*
D000925:Anticoagulants; D014859:Warfarin