Cancer and venous thromboembolism (VTE)

A systematic review was undertaken (1):

• prevalence of previously undiagnosed cancer in patients with unprovoked (idiopathic) VTE (venous thromboembolism) was 6.1% (95% CI, 5.0% to 7.1%) at baseline and 10.0% (CI, 8.6% to 11.3%) from baseline to 12 months
• risk of cancer was 4-fold greater in patients with unprovoked VTE (10%) than in those with a clear precipitating factor (2.6%)
• an extensive screening strategy using computed tomography of the abdomen and pelvis statistically significantly increased the proportion of previously undiagnosed cancer detected from 49.4% (CI, 40.2% to 58.5%) (with limited screening alone - history and examination, routine blood tests, CXR) to 69.7% (CI, 61.1% to 77.8%) in patients with unprovoked VTE
• previously undiagnosed cancer is frequent in patients with unprovoked VTE

Incidence of VTE in cancer patients

• compared with an incidence of about 0.1% in the general population
  • in a study by Cohen et al the absolute risk of VTE in people with cancer had (5.8 per per 100 person-years)
    • incidence rate of first VTE in patients with active cancer was 5.8%
    • overall incidence rate for recurrence was 9.6% (9.6 per per 100 person-years) with a peak at 22.1% (22.1 per per 100 person-years) in the first six months
    • mortality risk after VTE was considerable, with 64.5 % mortality after one year and 88.1 % after 10 years. VTE in patients with active cancer is common and associated with high recurrence and mortality rates (2)
  • Chemotherapy has been recognised as an independent predictorfor symptomatic VTE
    • risk of thrombosisin cancer patients receiving chemotherapy seems to vary based onthe stage of the disease, ranging from 3% to 5% in patients with early-stage cancer to 30% in those with metastatic or advanced malignancy (3,4)

Anticoagulation treatment for DVT or PE with active cancer (5)

• people with active cancer and confirmed proximal DVT or PE should be confirmed anticoagulation treatment for 3 to 6 months. Review at 3 to 6 months according to clinical need
  • for recommendations on treatment after 3 to 6 months see the linked item on long-term anticoagulation for secondary prevention.
    
    
• when choosing anticoagulation treatment for people with active cancer and confirmed proximal DVT or PE, take into account the tumour site, interactions with other drugs including those used to treat cancer, and the person's bleeding risk
  
  
• consider a direct-acting oral anticoagulant (DOAC) for people with active cancer and confirmed proximal DVT or PE
  
  
• if a DOAC is unsuitable consider LMWH alone or LMWH concurrently with a VKA (vitamin K antagonist) for at least 5 days, or until the INR is at least 2.0 in 2 consecutive readings, followed by a VKA on its own
  
  
• for people with confirmed DVT or PE and cancer that is in remission
  • for recommendations on treatment after 3 to 6 months see the linked item on long-term anticoagulation for secondary prevention

Comparison in mortality with isolated distal DVT (iDDVT) versus proximal DVT

• effect of iDDVT on mortality was similar to that of proximal DVT (pDVT) for most cancers except lung, colorectal, bladder, uterine, brain, and myeloma, where iDDVT was associated with a lesser association with mortality (6)

Relative incidence of VTE with gastrointestinal (GI) cancers (7)

• most VTE events happen close to onset of the GI cancer diagnosis and thrombogenicity differed by type of GI cancer, ranging from 7.8% in patients with pancreatic cancer to 3.6% in colorectal and patients with liver cancer
• prior VTE, heart failure, COPD, liver disease, CKD and DM were associated with increased risk of VTE

RCT (n=604) found that edoxaban treatment for 12 months was superior to 3 months in this population with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death (1% vs 7.2% in the 12 vs 3-month groups, (OR 0.13; 95% CI, 95% CI 0.03-0.44) (8)

Reference:

1. Carrier M, Le Gal G, Wells PS, Fergusson D, Ramsay T, Rodger MA.Systematic review: the Trousseau syndrome revisited: should we screen extensively for cancer in patients with venous thromboembolism? Ann Intern Med. 2008 Sep 2;149(5):323-33
2. Cohen AT et al. Epidemiology of first and recurrent venous thromboembolism in patients with active cancer. A population-based cohort study.
   Thrombosis and Haemostasis 2017;117:57-65.
3. Khorana AA, Connolly GC. Assessing risk of venous thromboembolism in the patient with cancer. Journal of Clinical Oncology 009;27(29):4839-47.
4. Timp JF et al. Epidemiology of cancer-associated venous thrombosis. Blood 2013;122:1712-23.
5. NICE (March 2020). Venous thromboembolic diseases: diagnosis, management and thrombophilia testing.
6. Mahajan A, Brunson A, Eldredge J, White RH, Keegan T, Wun T. Incidence and Outcomes Associated with 6841 Isolated Distal Deep Vein Thromboses in Patients with 13 Common Cancers. Thromb Haemost. 2022 Jan 17. doi: 10.1055/a-1742-0177.
7. Tonnnesen J, Pallisgaard J, Rasmussen PV, et al. Risk and timing of venous thromboembolism in patients with gastrointestinal cancer: a nationwide Danish cohort study. BMJ Open 2023;13:e062768. doi: 10.1136/bmjopen-2022-062768
8. Yamashita Y et al. Edoxaban for 12 Months Versus 3 Months in Cancer Patients With Isolated Distal Deep Vein Thrombosis (ONCO DVT study): An Open-label, Multicenter, Randomized Clinical Trial. Circulation August 28th 2023 https://doi.org/10.1161/CIRCULATIONAHA.123.066360