Catheter-Associated Thrombosis: Thromboprophylaxis or Not?
Authors: M. Levine, A.K. Kakkar
Journal: Journal of Clinical Oncology (2005)

Long-term indwelling central venous catheters are commonlyusedincancerpatientsfortheadministrationof chemotherapy, parenteral nutrition, and blood products and for the facilitation of the drawing of blood. Despite their important role in the delivery of quality patient care, central venous catheters can be associated with morbidity. One of the most common complications is catheter-related venous thrombosis. The extent of thrombosis associated with a central vein catheter can involve the catheter tip (ball-valve clot), the length of the catheter (fibrin sheath), orthecatheterizedvesselintheupperlimb,withorwithout the central vasculature of the neck or mediastinum. 1 In the 1990s, with the increasing use of central venous catheters in cancer patients, there was a clinical impression that catheter thrombosis was a common occurrence, associated with considerable morbidity. The results of two randomized trials provided evidence to support the use of prophylactic antithrombotic agents to prevent catheterassociated thrombosis. In a trial conducted by Monreal et al, 2 patients with a long-term subclavian venous catheter were randomly assigned either to 2,500 U of dalteparin low molecular weight heparin subcutaneously once daily for 90 days or to no prophylaxis. Upper limb venography was performed at 90 days or sooner if symptoms appeared. The trial was stopped early, after upper extremity thrombosis developed in one (6%) of 16 patients treated with low molecularweightheparincomparedwitheight(62%)of13 control patients (P.002). Six of the 29 thrombotic events were symptomatic. There was no increased risk of bleeding associated with the low molecular weight heparin. Bern et al 3 randomly assigned cancer patients with indwelling central venous catheters to either 1 mg of warfarin for 90 days or no treatment. This dosage regimen was based on the demonstrated efficacy of postoperative prophylaxis with 1 mg of warfarin in patients undergoing gynecologic surgery. 4 Venography was performed at 90 days. Onehundredtwenty-onepatientswererandomlyassigned, but only 80 patients completed the trial. Fifteen (37.5%) of 40 control patients developed thrombosis compared with four (9.5%) of 42 patients on warfarin (P .001). Seventeenofthethromboticepisodesweresymptomatic.Inmost cases, the prothrombin time was not prolonged, and there was no increase in bleeding associated with warfarin. After the publication of these studies, although there was lack of consensus on whether patients with central vein catheters should routinely receive thromboprophylaxis, low-dose warfarin was used in some clinical practices. In some patients, the prothrombin time was prolonged excessively because of interactions with chemotherapy drugs. 5 This issue contains two well-conducted randomized controlledtrialsbyVersoetal 6 andCoubanetal 7 evaluating thromboprophylaxis in cancer patients with central venous catheters. Both of these trials were double blind and, hence, provide higher quality evidence than the earlier published randomized trials that were not double blind. The two trials in this issue used different approaches in the choice of outcome for their studies. Verso et al 6 used mandatory venography of the upper limb at 42 days, whether the patient had symptoms or not. The use of this screening technique for venous thrombosis was adopted from prophylactic studies in patients undergoing orthopedic surgery, 8 with venography of the lower limbs at 7 to 10 days after surgery as the standard outcome measure used in clinical trials evaluating antithrombotics in this setting. Asymptomatic thrombosis in the deep veins of the lower limbs is considered a reasonable surrogate for the development of symptomatic venous thromboembolism because 20% of thrombi in the calf veins extend to the proximal deep veins and 50% of patients with proximal deep vein thrombosis have associated pulmonary embolism. Unfortunately, the natural history of catheter-associated thrombosis is not nearly as well defined as postoperative