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The presence of a central venous catheter and admission to the intensive care unit are the most important risk factors for deep venous thrombosis (DVT) in children. At least 18% of critically ill children with a catheter develop radiologically confirmed catheter-associated thrombosis. Clinically apparent thrombosis occurs in 3% of critically ill children with a catheter and is associated with 8 additional days of mechanical ventilation. Even when the thrombus is initially asymptomatic, 8 to 18% of critically ill children with catheter-associated thrombosis develop postthrombotic syndrome. Thrombosis is uncommon within 24 hours after insertion of a nontunneled catheter in critically ill children, but nearly all thrombi have developed by 4 days after insertion. Hypercoagulability during or immediately after insertion of the catheter plays an essential role in the development of thrombosis. Pharmacologic prophylaxis, including local anticoagulation with heparin-bonded catheter, has not been shown to reduce the risk of catheter-related thrombosis in children. Systemic anticoagulation in critically ill children started soon after the insertion of the catheter, however, may be beneficial. A multicenter clinical trial that is testing this hypothesis is currently underway.