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Peripheral Artery Disease: causes and consequences

Coronary Artery Disease: causes and consequences

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

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:

  • Higher rates of venous thromboembolism (VTE) recurrence and bleeding than patients without cancer2
  • Potential discontinuation or delay of cancer therapy3,4
  • A negative impact on quality of life3
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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
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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

 

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

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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

 

  • 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
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Risk factors for VTE in patients with cancer15,16

The risk of VTE also varies over the natural history of cancer; it is highest during hospitalization, chemotherapy and metastasis.1,17

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VTE risk varies over the natural history of cancer1,13,17

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

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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

 

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

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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

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