Expert Point of View: Fausto Roila, MD


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Thromboprophylaxis for patients with a central venous catheter is at present not recommended by the international oncologic associations. This is based on the results of four recent randomized controlled trials, three of them double-blind, in which there was no statistically significant difference between patients undergoing and not undergoing prophylaxis.1-4 In these studies, the incidence of symptomatic catheter-related venous thromboembolism was generally low, about 3% to 4%, compared with about 12% to 18% when asymptomatic patients were evaluated.

On the other hand, two old, open-label, randomized studies suggested a role for prophylaxis with warfarin or low-molecular-weight heparin.5,6 Dr. Lavau-Denes evaluated the efficacy of these two anticoagulant drugs vs no treatment in a study carried out in 407 patients. The incidence of central venous catheter–related thrombosis was significantly lower in patients receiving prophylaxis with the two anticoagulant drugs (8.1% [22/272] vs 14.8% [20/135], respectively). No difference was shown between warfarin and low-molecular-weight heparin. The anticoagulant prophylaxis did not significantly increase bleeding.

Study Limitations

The study by Dr. Lavau-Denes and her colleagues is important, but it has some limitations. It is not a blinded study, which is necessary to avoid selection bias. In fact, knowing the treatment received by the patients, the investigators might have performed more systematic Doppler ultrasound of the upper limbs and cervical veins or venography in the asymptomatic patients not submitted to anticoagulant prophylaxis, thus identifying in this subgroup of patients more catheter-related thrombosis. As a consequence, a possible statistically significant difference between patients undergoing and not undergoing thromboprophylaxis would be observed.

Furthermore, the incidence of thrombosis among symptomatic patients in the control arm—about 7%—is higher than the generally observed incidence of 3% to 4%. This could also be responsible for the significant difference observed in the study between patients receiving and not receiving anticoagulant prophylaxis.

The study is a single-center study that required 11 years to be completed. In this long period, many things could have changed—for example, the assessment of the response to anticoagulant therapy could have improved due to more advanced instrumentation. Finally, if we compare warfarin vs no treatment and low-molecular-weight heparin vs no treatment (as the authors have done for the evaluation of adverse events), the differences are not statistically significant.

Therefore, I think that the results of the study by Dr. Lavau-Denes should be confirmed by other double-blind, randomized clinical trials before the recommendations on thromboprophylaxis are changed. ■

Disclosure: Dr. Roila reported no potential conflicts of interest.

References

1. Heaton DC, Han DY, Inder A: Minidose (1 mg) warfarin as prophylaxis for central vein catheter thrombosis. Intern Med J 32:84-88, 2002.

2. Couban S, Goodyear M, Burnell M, et al: Randomized placebo-controlled study of low-dose warfarin for the prevention of central venous catheter-associated thrombosis in patients with cancer. J Clin Oncol 23:4063-4069, 2005.

3. Karthaus M, Kretzschmar A, Kroning H, et al: Dalteparin for prevention of catheter-related complications in cancer patients with central venous catheters: Final results of a double-blind, placebo–controlled phase III trial. Ann Oncol 17:289-296, 2006.

4. Verso M, Agnelli G, Bertoglio S, et al: Enoxaparin for the prevention of venous thromboembolism associated with central vein catheter: A double-blind, placebo-controlled, randomized studies in cancer patients. J Clin Oncol 23:4057-4062, 2005.

5. Bern MM, Lokich JJ, Wallach SR, et al: Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomised prospective trial. Ann Intern Med 112:423-428, 1990.

6. Monreal M, Alastrue A, Rull M, et al: Upper extremity deep venous thrombosis in cancer patients with venous access device-prophylaxis with a low molecular weight heparin (Fragmin). Thromb Haemost 75:251-253, 1996.

Dr. Roila is Director, Medical Oncology Division, Santa Maria Hospital, Terni, Italy


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