Does Prophylaxis Prevent Catheter-related Thrombosis?

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In ambulatory patients with cancer, the risk of catheter-related deep-vein thrombosis can be reduced by almost half with anticoagulation prophylaxis, according to a single-center French study presented at the 2012 European Society for Medical Oncology (ESMO) Congress in Vienna.1

Catheters implanted for chemotherapy delivery create a risk for deep-vein thrombosis that ranges from 0.3% to 28.3% for symptomatic events, rising to 27% to 66% when asymptomatic episodes are included, said Sandrine Lavau-Denes, MD, of the University Hospital Limoges in France.

“But the current guidelines of ASCO, the American College of Chest Physicians, and the French National Federation of the League of Centers Against Cancer do not recommend prophylactic anticoagulant treatment for cancer outpatients,” Dr. Lavau-Denes noted. “In recent studies and meta-analyses, the results are still contradictory, perhaps because of the heterogeneity of the screened patients.”

Randomized Trial

To help resolve the controversy, Dr. Lavau-Denes and colleagues conducted a phase III prospective, randomized, open-label trial spanning a 10-year period at their center (1999–2010), comparing a prophylactic strategy to no prophylaxis during 3 months of chemotherapy among 420 patients with advanced solid tumors.

“We found that prophylaxis with either warfarin or low-molecular-weight heparin was effective in preventing thrombotic events, and there was no increase in bleeding with prophylaxis,” Dr. Lavau-Denes reported.

The primary endpoint was the rate of symptomatic and asymptomatic catheter-related deep-vein thrombosis of the ipsilateral upper limbs and cervical veins of patients, excluding intraluminal thrombosis.

The study randomly assigned patients starting a first line of treatment—142 to low-molecular-weight heparin, 138 to warfarin, and 140 to a control arm. Patients were evaluated at baseline and on day 90 (sooner, in the case of symptoms), using Doppler ultrasound of the upper limbs and cervical veins, and venography.

Effectiveness of Prophylaxis

Among 407 evaluable patients, catheter-related deep-vein thrombosis occurred in 42 patients (10.3%), 30 of whom were asymptomatic. This included 20 (14.8%) of 135 patients in the control arm and 22 (8.1%) of 272 patients receiving either warfarin or low-molecular-weight heparin. Warfarin and low-molecular-weight heparin had no difference in efficacy.

Thromboprophylaxis was associated with a 45% reduction in risk that was statistically significant (P = .0357), Dr. Lavau-Denes reported.

The events were symptomatic in 6.7% of the control arm, and in 1.1% of the combined-intervention arm. Asymptomatic events occurred in 8.1% and 7.0% of the two groups, respectively.

Unrelated deep-vein thromboses were also prevented, occurring in 5.1% of the control arm and 0.7% of the intervention arm. For all but one of these 9 patients, the episode was symptomatic.

Adverse Events

The preventive effect was achieved without a significant increase in adverse events. Bleeding occurred in 0.7% of controls, 2.2% of the low-molecular-weight heparin arm, and 4.5% of the warfarin arm (P = .1361). However, there was an increase in thrombopenia among patients receiving thromboprophylaxis (P < .0001), particularly with low-molecular-weight heparin; this effect was grade 3/4 in only 12 (8.8%), 4 (3.0%), and 7 (5.0%), respectively, with no significant difference among the arms (P = .1039).

Approximately one-quarter of patients discontinued prophylaxis, with no difference among the arms. For 12.5% of the control arm, the reason for discontinuation was the occurrence of a thrombotic event, compared to 2.2% of the warfarin arm and 2.2% of the low-molecular-weight heparin arm.

Overall, these results suggest that thromboprophylaxis can benefit patients with cancer receiving chemotherapy. “We think that these new results should lead to a new [consideration] of the guidelines,” said Dr. Lavau-Denes. ■

Disclosure:  Dr. Lavau-Denes reported no potential conflicts of interest.


1. Tubiana-Mathieu N, Lavau-Denes S, Lacroix P, et al: Prophylaxis of catheter-related deep vein thrombosis in cancer patients with low-dose warfarin, low molecular weight heparin, or control: A randomized, controlled, phase III study. 2012 ESMO Congress. Abstract 15460. Presented October 1, 2012.

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