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Catheter-Related Thrombosis Can Be Prevented

TOP - December 2012 VOL 5, NO 8 published on December 20, 2012 in Supportive Care
Caroline Helwick

Anticoagulation prophylaxis is effective in preventing both symptomatic and asymptomatic catheter-related deep vein thrombosis in ambulatory cancer patients with locally advanced or metastatic solid tumors, French investigators reported at the European Society for Medical Oncology (ESMO) 2012 Congress, held in Vienna, Austria.1

Among cancer patients who have catheters in place for chemotherapy, catheter-related deep vein thrombosis causes morbidity and mortality. The incidence of symptomatic events ranges from 0.3% to 28.3%, and the incidence rises
to 27% to 66% when asymptomatic episodes are included.

Current guidelines from American and European societies do not recommend prophylactic anticoagulation for cancer outpatients, but symptomatic catheter-related deep vein thrombosis is still a subject of active research, and the value of prophylaxis in this population is controversial, said Sandrine Lavau-Denes, MD, of the University Hospital at Limoges in France.

Lavau-Denes reported the results of a phase 3 single-center prospective, randomized, open-label trial, conducted over a 10-year period (1999-2010), that compared a prophylactic strategy to no prophylaxis over 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,” said Lavau-Denes.

The study was initiated prior to the publication of the current guidelines. The primary end point was the rate of symptomatic and asymptomatic catheter-related deep vein thromboses of the ipsilateral upper limbs and cervical veins of patients who received, versus those who did not receive, thromboprophylaxis. It excluded intra­luminal thrombosis.

Investigators randomized 142 patients starting a first line of treatment to low-molecular-weight heparin (at the recommended dose), 138 to warfarin (1 mg/day), 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
In 407 evaluable patients, 42 catheter-related deep vein thromboses occurred (10.3%), 30 (15.1%) of which were asymptomatic. This included 20 of 135 (14.8%) patients in the control arm and 22 of 272 (8.1%) patients receiving either warfarin or low-molecular-weight heparin.

The effect of prophylaxis amounted to a 45% reduction in risk that was statistically significant (P = .0357). Warfarin and low-molecular-weight heparin were equally effective, Lavau-Denes noted.

Rates of symptomatic events were 6.7% in controls, versus 1.1% after prophylaxis; asymptomatic events occurred in 8.1% and 7.0%, respectively. Unrelated deep vein thromboses also were prevented.

Adverse events were not significantly increased with thromboprophylaxis. 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 in patients receiving thromboprophylaxis (P <.0001), particularly with low-mo­lecular-weight heparin. However, this was grade 3/4 in only 12 (8.8%), 4 (3.0%), and 7 (5.0%) patients, respectively, with no difference among the arms (P = .1039), she said.

Prophylaxis was discontinued by 25% in the control arm, 27% in the warfarin arm, and 33% in the low-mo­lecular-weight heparin arm. For 12.5% of patients in the control arm the reason was the occurrence of a thrombotic event, compared with 2.2% in the warfarin arm and 2.2% in the low-mo­lecular-weight heparin arm.

Who Should Receive Prophylaxis?
Fausto Roila, MD, of Terni, Italy, who chairs ESMO’s Supportive Care Track, reiterated that routine prophylaxis for ambulatory patients with solid tumors is not recommended by any society, except when patients are considered
at high risk. However, he noted, “Thrombosis is a potentially deadly complication, and it is not rare.”

Therefore, Roila suggested that primary prophylaxis be considered under the following circumstances:

  • The incidence within one’s institution is 8% to 10%
  • The tip of the central venous catheter is not positioned at the junction between the atrium and the vena cava
  • The patient has factor V Leiden mutation or a previous venous thromboembolism
  • The patient has mediastinal syndrome

Reference

  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. Presented at: European Society for Medical Oncology 2012 Congress; October 1, 2012; Vienna, Austria. Abstract 1546O PR.
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Last modified: September 9, 2019