occult malignancy and venous thromboembolism (VTE)

Last edited 11/2021 and last reviewed 01/2022

Cancer is an established risk factor for venous thromboembolism (1).

A relationship between thrombosis and malignancy has been suspected since the times of Virchow and Trousseau

• Trousseau is considered to be the first to have recognised a relation between venous thromboembolism (VTE) and malignancy (2)
• in 1935 Illtyd James and Matheson report the observation of a patient with occult cancer at time of his venous thrombosis (3)

Idiopathic VTE and concomitant cancer:

• prevalence of occult cancer in patients with secondary VTE is comparable with the prevalence of cancer in the general population, while the prevalence of occult cancer in patients with idiopathic VTE is 4-10% (2)
• a large prospective follow-up study was undertaken by Oudega et al (4):
• a total of 430 consecutive patients without known malignancy, but with proven DVT were included in the study and compared with a control group of 442 primary care patients, matched according to age and sex. Previously unrecognised, occult malignancy was considered present if a new malignancy was diagnosed within 2 years following DVT diagnosis (DVT group) or inclusion in the control group. Patients with DVT were categorised in to those with unprovoked idiopathic DVT and those with risk factors for DVT (that is, secondary DVT)
• during the 2-year follow-up period, a new malignancy was diagnosed 3.6 times more often in patients with idiopathic DVT than in the control group (2-year incidence: 7.4% and 2.0%, respectively). The incidence in patients with secondary DVT was 2.6%; similar to the control patients
• the study authors stated "Patients with idiopathic (unprovoked) DVT have an elevated risk of malignancy. The risk in patients with known risk factors (secondary DVT), is nearly the same as in the population at large. These findings in primary care are the same as those known from secondary care"

Guidance suggests that (5):

• Patients with an unprovoked VTE should undergo a limited cancer screening and age- and gender-specific cancer screening. A limited cancer screening includes a clinical history, physical examination, laboratory tests (FBC, calcium, urinalysis, and liver function tests), and chest radiography. Age- and gender-specific cancer screening (i.e., breast, cervix, colon, and prostate cancer) should follow national recommendations

NICE state (6):

• several cancers to consider, including urogenital, breast, colorectal or lung
• carry out an assessment for additional symptoms, signs or findings that may help to clarify which cancer is most likely
• consider urgent investigation or a suspected cancer pathway referral (for an appointment within 2 weeks)

Reference:

• Hansson PO et al. Recurrent venous thromboembolism after deep vein thrombosis. Incidence and risk factors. Arch Intern Med 2000;160: 769-74.
• Otten HM, PrinsMH.Venous thromboembolismand occult malignancy. Thromb Res 2001; 102:V187–V194.
• Illtyd James TGI, Matheson NM (1935) Thrombophlebitis in cancer. Practitioner 134: 683–684
• Oudega R et al. Deep vein thrombosis in primary care: possible malignancy? British Journal of General Practice 2006; 56: 693–696.
• Delluc A., Antic D., Lecumberri R., Ay C., Meyer G., Carrier M. Occult cancer screening in patients with venous thromboembolism: Guidance from the SSC of the ISTH. J. Thromb. Haemost. 2017;15:2076–2079. doi: 10.1111/jth.13791
• NICE (June 2015). Suspected cancer: recognition and referral