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Introduction to Cancer-Associated Thrombosis
Patients with cancer are at risk of cancer-associated thrombosis, an event associated with poor prognosis. Various risk factors can contribute to the cancer-induced state of hypercoagulability
In this section:
Burden of desease
Cancer-associated thrombosis (CAT) is a highly prevalent complication of cancer.1 CAT adds to the emotional and symptomatic burden of cancer , with patients experiencing:
Risk of events in patients receiving anticoagulation therapy for VTE2
VTE is also a leading cause of mortality in patients with cancer.5,6
- Patients with cancer and VTE have a 30-fold increased risk of death compared with patients without cancer or VTE7
Hazard ratios for the difference in mortality per 100 patient-years in patients with VTE and/or cancer compared with patients without VTE or cancer7
- The risk is usually highest during the first year after cancer diagnosis8
VTE is also associated with a threefold increase in hospitalizations and higher healthcare costs in patients with cancer compared with patients without cancer3,5
Epidemiology
Approximately 20% of all VTE cases occur in patients with cancer.3
VTE has been shown to be present in up to 50% of patients with cancer at autopsy.3
Previous studies have reported that VTE occurs in 0.5-20% of patients with cancer, with highly variable risk depending on factors such as cancer type.8-12
Cumulative risk of VTE in patients with cancer undergoing chemotherapy13
Although the link between cancer and thrombosis is well established, CAT is undertreated, which compounds its status as a major health issue.14
Risk factors
- Patients with cancer have a four- to sevenfold increased risk of VTE compared with patients without cancer (see Epidemiology)4,15
- Individual patient risk of CAT varies according to numerous risk factors, including those related to the patient, tumour and treatment, in addition to those indicated by elevated biomarker levels15
The risk of VTE also varies over the natural history of cancer; it is highest during hospitalization, chemotherapy and metastasis.1,17
VTE as a predictor of occult cancer
Up to 10% of patients with VTE that appears to have no cause are diagnosed with cancer within a year after the thrombotic event, suggesting that occult cancer was the cause of thrombosis.5
Occult cancer as an underlying cause of unprovoked VTE5
A recently published consensus suggests that patients with unprovoked VTE should undergo:5
- A thorough medical history and physical examination
- Basic laboratory investigations (complete blood counts, metabolic profile and liver function tests); and
- A chest X-ray
Pathogenesis
The multifactorial pathogenesis of CAT involves various overlapping pathways influenced by a multitude of risk factors for disease.15
Malignant tissue, chemotherapy and other contributing factors (e.g. surgery-induced endothelia damage and venous stasis from immobility) can induce a hypercoagulable state through the activation of inflammatory cytokines, the coagulation pathway and inhibition of fibrinolytic activity.15
Pathophysiology of CAT.15 Tumour cells can activate the coagulation pathway and induce a hypercoagulable state through the release of procoagulant factors (e.g. TF) and pro-inflammatory cytokines. Tumour cells can also inhibit fibrinolysis (not shown). Chemotherapy can create a hypercoagulable state via endothelial cell damage and inducing inflammation
References
- Cohen AT, Katholing A, Rietbrock S et al. Epidemiology of first and recurrent venous thromboembolism in patients with active cancer. A population-based cohort study. Thromb Haemost 2017;117:57–65. Return to content
- Prandoni P, Lensing AWA, Piccioli A et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002;100:3484–3488. Return to content
- Lyman GH. Venous thromboembolism in the patient with cancer: focus on burden of disease and benefits of thromboprophylaxis. Cancer 2011;117:1334–1349. Return to content
- Fuentes HE, Tafur AJ, Caprini JA. Cancer-associated thrombosis. Dis Mon 2016;62:121–158. Return to content
- Khorana AA, Carrier M, Garcia DA, Lee AYY. Guidance for the prevention and treatment of cancer-associated venous thromboembolism. J Thromb Thrombolysis 2016;41:81–91. Return to content
- Khorana AA, Francis CW, Culakova E et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 2007;5:632–634. Return to content
- Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC. Epidemiology of cancer-associated venous thrombosis. Blood 2013;122:1712–1723. Return to content
- Chew HK, Wun T, Harvey D et al. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006;166:458–464. Return to content
- Stein PD, Beemath A, Meyers FA et al. Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med 2006;119:60–68. Return to content
- Lee AY. Management of thrombosis in cancer: primary prevention and secondary prophylaxis. Br J Haematol 2005;128:291–302. Return to content
- Sallah S, Wan JY, Nguyen NP. Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb Haemost 2002;87:575–579. Return to content
- Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med 2012;9:e1001275. Return to content
- Lyman GH, Eckert L, Wang Y et al. Venous thromboembolism risk in patients with cancer receiving chemotherapy: a real-world analysis. Oncologist 2013;18:1321–1329. Return to content
- Khalil J, Bensaid B, Elkacemi H et al. Venous thromboembolism in cancer patients: an underestimated major health problem. World J Surg Oncol 2015;13:204. Return to content
- Ay C, Pabinger I, Cohen AT. Cancer-associated venous thromboembolism: burden, mechanisms, and management. Thromb Haemost 2017;117:219–230. Return to content
- Malaponte G, Signorelli SS, Bevelacqua V et al. Increased levels of NF-kB-dependent markers in cancer-associated deep venous thrombosis. PLoS One 2015;10:e0132496. Return to content
- Rao M, Francis C, Khorana A. Who's at risk for thrombosis? Approaches to risk stratifying cancer patients. In: Francis C, Khorana A (eds). Cancer-Associated Thrombosis: New Findings in Translational Science, Prevention, and Treatment. Healthcare USA, Inc; New York, NY; 2007. p. 169-192. Return to content
See Also
Peripheral Artery Disease: causes and consequences
See Also
Coronary Artery Disease: causes and consequences
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Updated date 10/10/2022
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