More on Antithrombotic Prophylaxis for Patients with Central Venous Devices
More on Antithrombotic Prophylaxis for Patients with Central Venous Devices
Abstract & Commentary
By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
Synopsis: The use of antithrombotic prophylaxis with either unfractionated heparin, low molecular weight heparin or low-dose warfarin in patients with cancer and indwelling central venous devices was examined in a multi-institutional observational study. Although catheter-associated thromboses were not apparently reduced, the incidence of non-catheter related thrombotic events was, and overall mortality was less for those who received continuous antithrombotic prophylaxis.
Source: Fagnani D, et al. Ann Oncology. 2007;18:551-555.
There have been conflicting studies regarding the advisability of antithrombotic prophylaxis (with low-molecular weight heparin [LMWH], unfractionated heparin, or low-dose warfarin) in patients with cancer for whom indwelling central venous catheters have been employed.1-5 Fagnani and collaborators from the POLONORD Group in northern Italy report their observational prospective study designed to assess the management of central venous devices (CVDs) in patients treated in community practice, particularly in the context of antithrombotic prophylaxis (AP). Cancer patients from 18 hospital oncology units throughout northern Italy were enrolled over a 30 month period (through June, 2005) if they had a totally implantable CVD (port), an indwelling central venous catheter (CVC), or a peripherally-inserted catheter (PICC). The type of catheter used was at the discretion of the physicians at each hospital as was the decision of whether or not to prescribe antithrombotic prophylaxis. Data analyzed included demographic details, type of CVD, position of the catheter tip, type of tumor and stage, history with regard to prior thrombotic events, and past and current cancer treatments (chemotherapy, radiotherapy, hormone therapy and growth factors). One feature that separates this survey from others is the length of follow-up. Evaluations on each patient were scheduled every 4 months during the first year, every 6 months during the second and third years or until removal of the CVD. During follow-up, a record was kept of any catheter-related complications (eg, infection, pneumothorax, catheter fracture, etc.), systemic thromboembolic events (eg, pulmonary embolism, DVT other than in the vicinity of the CVD, supraventricular tachycardia, etc.), CVD removal, bleeding episodes (eg, intracranial or retroperitoneal hemorrhage), and the course of the neoplastic disease (progression of disease, death). Furthermore, the type of antithrombotic prophylaxis was recorded as either associated with the procedure (limited to 48 hours at the time of catheter insertion) or continuous, and the type of anti-thrombotic therapy documented. The drugs employed (mini-dose warfarin per the Levine regimen6 (initially 1 mg/day, tapered to maintain INR of 1.3-1.9), LMWH, or unfractionated heparin and duration of treatment were also recorded.
During the 2½ years of study, 1410 consecutive patients were enrolled and 1390 were seen at least once in the 6 month median follow-up. There was no difference in catheter-related thrombosis in patients given antithrombotic prophylaxis or not (2.8% and 2.2%) and no major bleeding events were recorded. However, systemic (ie, not in the vicinity of the catheter) venous thrombus embolic events, including superficial thromboses and pulmonary embolism, were less frequent with antithrombotic prophylaxis (4% vs 8.2%, P = 0.005) and mortality was lower (25% vs 44%, P = 0.0001). Upon multilogistic regression analysis, only advanced cancer and no antithrombotic prophylaxis were significantly associated with mortality.
Commentary
This is a very curious finding. Although antithrombotic prophylaxis did not prevent catheter-related thrombosis, it did seem to influence systemic thromboses including the occurrence of pulmonary emboli and reduce overall mortality. It's difficult not to be a little bit energized by this finding, albeit derived from an observational, non-randomized study. Reluctantly, we must accept that AP is ineffective at reducing catheter-associated thrombus formation as the current results confirm what several other studies have indicated previously.2, 5 Despite the theoretical appeal of such an approach, there is no evidence that anticoagulation prevents catheter-associated thrombus in cancer patients. The lack of effect in the current study may be the result of the relatively low incidence of catheter-associated thrombus in either group, those receiving prophylaxis (2.8%) and those not (2.2%). This, in turn, may reflect improved technique, catheter positioning and the use of less thrombogenic devices. Furthermore, because this was a pattern-of-care type study, participating physicians may have chosen to use antithrombotic prophylaxis for those patients considered at highest risk (advanced disease, history of prior DVT, etc) and accordingly, the 2.8% incidence might be lower than what would have been observed had this group not been treated.
That antithrombotic prophylaxis influenced non-catheter associated thrombotic occurrence is remarkable and needs further explanation. The majority of patients who received prophylaxis were given low-dose warfarin and there have been previous conflicting reports on the value of such treatment in preventing venous thrombosis in cancer patients.6, 7 The current study was large, well designed and of sufficient duration to merit attention. The data would suggest that antithrombotic prophylaxis for patients with advanced cancer with a high risk for venous thrombosis achieve more favorable outcomes (less thromboembolic events and longer overall survival). However, because of the inherent risks associated with anticoagulation, a randomized, prospective study in carefully selected patients is called for.
References
1. Bern MM, et al. Ann Intern Med. 1990;112:423-428.
2. Couban S, et al. J Clin Oncol. 2005;23:4063-4069.
3. Karthaus M, et al. Ann Oncol. 2006;17:289-296.
4. Monreal M, et al. Thromb Haemost. 1996;75:251-253.
5. Verso M, et al. J Clin Oncol. 2005;23(18):4057-4062.
6. Levine M, et al. Lancet. 1994;343(8902):886-889.
7. Cortelezzi A, et al. Br J Haematol. 2005;129:811-817.
The use of antithrombotic prophylaxis with either unfractionated heparin, low molecular weight heparin or low-dose warfarin in patients with cancer and indwelling central venous devices was examined in a multi-institutional observational study.Subscribe Now for Access
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