Perspective:

This paper reviews the risks of venous thromboembolism (VTE) in ambulatory patients with cancer as well as approaches to VTE prophylaxis. The following are key points in the review:

1. VTE risk is significant in many cancer patients. The risk of developing VTE is 4-7 times higher among patients with cancer compared to patients without cancer. In fact, VTE is the second leading cause of death in cancer patients. Some studies suggest that survival rates of cancer patients with VTE are one-third the survival rate of cancer patients without VTE.

2. The risk of VTE in cancer patients can be estimated using the Khorana score. The score ranges from 0-7 based on the type of cancer, platelet count, hemoglobin level, white-cell count, and body mass index (BMI). Low-risk patients (score = 0) have 0.3% incidence of VTE compared to intermediate-risk patients (score = 1 or 2, 2% incidence) and high-risk patients (score ≥3, 6.7% incidence).

3. Other important risk factors for cancer-associated VTE include prolonged immobilization, the use of hormone therapy and angiogenesis inhibitors, prior VTE, and compression of vascular structures by tumor or adenopathy.

4. Two trials (PROTECHT and SAVE-ONCO) randomized cancer patients to VTE prophylaxis or placebo. Both trials showed a significant reduction in VTE with the use of pharmacological prophylaxis (nadroparin in the PROTECHT study and semuloparin in the SAVE-ONCO study). It is notable that both studies had low rates of VTE in the placebo groups (3-4%).

5. A recent retrospective study suggests that rates of cancer-associated VTE may be higher than were found in both of the randomized trials. This study reported a rate of VTE above 7% within 3.5 months and 13.5% within 1 year after starting chemotherapy.

6. The risk of bleeding associated with VTE prophylaxis is higher in cancer patients than noncancer patients. However, this risk of bleeding is less than in patients receiving full-strength anticoagulation, suggesting that prophylaxis to prevent a VTE is often justified.

7. The author’s recommendations for VTE prophylaxis are compared to three leading guideline statements from the American College of Chest Physicians, American Society of Clinical Oncology, and the National Comprehensive Cancer Network. All advise against the use of routine prophylaxis in most ambulatory cancer patients. However, an exception is made for patients with multiple myeloma who are treated with thalidomide, lenalidomide, or chemotherapy with dexamethasone because of very high rates of VTE (23-75%).

8. If VTE prophylaxis is indicated, use of either enoxaparin 40 mg daily or warfarin is recommended.