CANCER-ASSOCIATED THROMBOSIS

PATIENTS WITH CANCER ARE AT RISK FOR VTE

VTE risk is up to ninefold higher in patients with cancer compared to non-cancer patients within 12 months of diagnosis.1

Cancer patients have several conditions that predispose them to thrombus generation.2-4 These patients are generally in a hypercoagulable or prothrombotic state, as they usually present with abnormalities in each component of the Virchow’s triad.4

Hospitalised cancer patients and those receiving chemotherapy are at the greatest risk of developing VTE3

Cancer-associated thrombosis

Cancer-associated thrombosis (CAT) is a highly prevalent common complication and is frequently diagnosed in patients with cancer4 (in up to 20% of cancer patients5). Major consequences of CAT adding to the emotional and symptomatic burden of cancer are:6

  • Higher risk of recurrent thrombosis, and higher risk of bleeding during anticoagulation, than patients without cancer.7
  • Increased hospitalisation rates and decreased survival time.8
  • Potential discontinuation or delay of cancer therapy.8,9
  • A negative impact on quality of life.8

Epidemiology

Following cancer itself, VTE is second leading cause of mortality in patients with cancer.10,11

Patients with cancer and VTE have a 30-fold increased risk of death compared with patients without cancer or VTE.12 The risk is usually highest during the first year after cancer diagnosis.13

VTE is also associated with a threefold increase in hospitalizations and higher healthcare costs in patients with cancer compared with patients without cancer.8,10

Approximately 20% of all VTE cases occur in patients with cancer8, with up to 50% of these cases are often incidentally diagnosed.5

 

Causes of death in cancer patients receiving outpatient chemotherapy.11 This graph is based on US data. Causes of death in 4466 cancer patients receiving outpatient chemotherapy. Causes of death exceed total number of deaths because six patients had more than one cause of death identified.

Related risk factors for CAT include

Patient related risk factors3-4


  • Advanced age
  • Female sex
  • Race
  • Prior history of VTE
  • Patient comorbidities
  • Prolonged immobiliastion
  • Inherited thrombophilic factors

 

Cancer related risk factors3-4


  • Site: hematological malignancies, lung, pancreas, stomach, brain, kidney
  • Stage: advanced stage and initial period after diagnosis
  • Histology of cancer
  • Time after diagnosis

 

 

 

 

Cancer treatment related risk factors3-4,15


  • Surgery and hospitalisation
  • Chemotherapy and hormonal therapy
  • Anti-angiogenic therapy
  • Erythropoiesis-stimulating agents

 

Biomarkers3,15


  • Platelet count (>350000 per µL)
  • Leukocyte count (>11000 per µL)
  • D-dimer
  • Tissue factor expression by tumour cells
  • Circulating tissue factor
  • Soluble P-selectin
  • C-reactive protein

 

The related risk factors mentioned above is not a comprehensive list.

Pathophysiology of CAT4,14

The pathogenesis of cancer associated thrombosis is complex, and not entirely understood. What’s more, the multiple overlapping pathways leading to thrombosis are influenced by the type and stage of the tumour itself.

Numerous factors, including malignant tissue, chemotherapy and environmental factors (e.g. surgery-induced endothelia damage and venous stasis from immobility) can induce a hypercoagulable state.

On a cellular level, the production of procoagulants by tumour cells, the suppression of fibrinolytic activity and platelet activation a prothrombotic state is established.

Virchow’s triad in patients with cancer15

Statis
Hypercoagulability
Endothelial Injury

Prolonged bed rest – patient immobility/reduced mobility

Compression of blood vessels by tumour

More pro-coagulation factors due to hypoxia and/or inflammation

Tumour cytokines and pro-angiogenic factors

Recent major surgery

Increase in overall platelet activity and decrease in anticoagulant activity

Decrease in fibrinolytic activity

Current chemotherapy, anti-angiogenic therapy

Direct invasion by tumour

Prolonged use of central venous catheters

Endothelial damage by chemotherapy

Effect of tumour cytokines on vascular endothelium

Radiation therapy (late phase complication)

Adapted from Mukai M et al. 2018, Lynman GH et al. 2011 and Khorana AA et al. 2016.

References

  1. Mulder et al. Blood. 2021,137(14):1959–1969
  2. Khorana, A.A. et al. J. Clin. Oncol. 2009, 27: 4839–4847
  3. Fernandes CJ et al. Eur Respir Rev. 2019, 28: 180119
  4. Abdol Razak NB et al. Cancers. 2018, 10, 380
  5. S Riondino. Cancers. 2019 Jan; 11(1): 95
  6. Feelings and cancer. Available at: www.cancer.gov/about-cancer/coping/feelings. Accessed on February 2022
  7. Prandoni P, et al. Blood 2002;100:3484–3488.
  8. Lyman GH. Cancer 2011;117:1334–1349.
  9. Fuentes HE, Tafur AJ, Caprini JA. Dis Mon 2016;62:121–158.
  10. Khorana AA, et al. J Thromb Thrombolysis 2016;41:81–91.
  11. Khorana AA, et al. J Thromb Haemost 2007;5:632–634.
  12. Timp JF, et al. Blood 2013;122:1712–1723.
  13. Chew HK, et al.. Arch Intern Med 2006;166:458–464.
  14. Ay C et al. Thromb Haemost. 2017; 117: 219–230.
  15. Mukai M et al. Journal of Cardiology. 72 (2018) 89–93

MAT-GB-2000453 (v5.0) Date of preparation: March 2022