Bayer Pharma AG

Essence of this Article

Patients with cancer face an increased risk of venous thromboembolism (VTE) as malignancy is associated with a hypercoagulable state and the use of chemotherapy agents may also contribute to an increased risk. In fact, VTE is a significant cause of morbidity and mortality in patients with cancer. Risk factors for cancer-associated VTE include: tumour type; age; stage of cancer; and VTE history. Risk stratification and use of biomarker-based approaches may assist in the provision of targeted thromboprophylaxis. The use of a validated predictive model for VTE risk in patients with cancer receiving chemotherapy may also enable clinicians to determine whether patients are at particularly high risk of VTE.

Cancer increases the risk of venous thromboembolism

Malignancy is associated with a hypercoagulable state as a result of the release of inflammatory cytokines, activation of the clotting system, a decrease in the level of natural anticoagulants and impaired fibrinolysis.277 The use of chemotherapy agents in patients with cancer may also contribute to an increased risk of venous thromboembolism (VTE).278

  • The cumulative 2-year incidence rate of VTE in a cohort of >200,000 patients with cancer was 1.6%279
  • Approximately 20% of all VTE cases occur in patients with cancer278
  • VTE affects up to 20% of patients with cancer before death and has been reported in up to half of patients at the time of postmortem examination278
  • The frequency of VTE in patients undergoing cancer surgery is roughly twice that seen in patients without malignancies who have similar operations280

VTE is a significant cause of morbidity and mortality in patients with cancer and is a significant predictor of increased mortality during the first year, among all types and stages of cancer.278, 279

Risk factors for venous thromboembolism in patients with cancer

The risk of thrombosis is greatest in the first year after the diagnosis of cancer.279, 281 Risk factors for cancer-associated VTE include:

  • Tumour type
  • Older age
  • Poorer performance status
  • VTE history282
  • Advanced stage of cancer278
  • Use of central venous catheters283

Certain medications used to treat cancer, such as tamoxifen and erythropoietin, increase the risk of VTE. In addition, chemotherapeutic agents that suppress blood vessel formation (e.g. thalidomide, lenalidomide and bevacizumab) have been associated with a high rate of VTE.284 However, a more-recent pooled analysis of phase II and III clinical data showed that adjuvant therapy with bevacizumab was not associated with an increased risk of VTE.282

Certain cancers are associated with a higher risk of VTE (e.g. pancreatic, gastric, colon, brain, kidney, ovarian, prostate, haematological and lung), and metastatic cancer confers a greater risk than primary tumours.284, 285

Biomarkers associated with increased risk of VTE in patients with cancer include elevated leukocyte count, elevated platelet count, levels of tissue factor, P-selectin and D-dimer.286

Risk stratification and use of biomarker-based approaches may assist in the provision of targeted thromboprophylaxis. A validated predictive model for VTE risk in patients with cancer receiving chemotherapy enables clinicians to determine whether patients are at particularly high risk of VTE.287

Predictive model for chemotherapy-associated VTE287

Patient characteristic Risk score
Site of cancer Very high risk (stomach, pancreas)a 2
High risk (lung, lymphoma, gynaecologic, bladder, testicular)b 1
Prechemotherapy platelet count ≥350 × 109/l 1
Haemoglobin <100 g/l or use of RBC growth factors 1
Prechemotherapy leucocyte count >11 × 109/l 1
Body mass index ≥35 kg/m2 1
aVTE rates 3-fold or higher than the average risk for the population;
bVTE rates higher than average.
RBC, red blood cell; VTE venous thromboembolism.

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Using this predictive model, patients were considered low-risk if they had a score of 0, intermediate-risk if they had a score of 1–2 and high-risk if they had a score of ≥3.287


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