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Cancer in patients with unexplained blood clots
Explains the link between cancer and blood clots of unknown cause, and what tests are appropriate



Introduction
Unexplained clots and cancer: what is the link?
Is routine extensive screening for cancer appropriate?
What tests should be performed?
Summary
References

Introduction
People who develop a blood clot (thrombosis) are known to be more likely than the general population to be diagnosed with cancer within a year or two. The risk is particularly increased in patients with unexplained blood clots-those that cannot be attributed, after routine assessment, to causes such as a family history of blood clots, limb trauma, pregnancy, and prolonged immobilization due to surgery or a medical disorder.

This article explains why cancer may be associated with blood clots, in particular unexplained clots, and discusses appropriate tests that a physician might request in order to check for cancer.


Unexplained clots and cancer: what is the link?

The current evidence suggests that patients hospitalized with a blood clot have an increased risk of being diagnosed with cancer soon after. One large study found that 4% of patients with a blood clot had a new cancer diagnosis at the time of their hospital admission or within the 1st year afterwards—about 4 times more than would be expected in the general population.

This increased risk is not spread equally among patients with blood clots: certain subgroups of patients are more likely than others to develop cancer. Much of the increased risk seems to occur in those whose blood clots are of unknown cause (known as idiopathic thrombosis). In 1 study, about 10% of patients with unexplained clots were diagnosed with cancer within 2 years. So, the chance of a patient with unexplained blood clots developing cancer is about 2 times higher than for a patient with blood clots of known cause. Research has also shown that cancer is detected within 6–12 months of the clot occurring in most patients, after which the risk falls to near-normal levels. Cancers of the pancreas, ovary, liver, and brain seem slightly more likely to occur after a blood clot than cancers in other parts of the body.

Why might patients with unexplained clots have an increased risk of cancer? One reason is that cancer, even at a very early stage that is not yet causing noticeable symptoms, can induce clotting. Therefore, cancer is associated with a hypercoagulable state (increased blood clotting). The blood clot may actually be one of the 1st signs that a patient has developed cancer. Also, patients hospitalized with a blood clot will subsequently undergo a wide range of tests in order to find out the likely cause; therefore, it is perhaps more likely that any underlying cancer (even if it is not a cause of the clot) will be detected, compared with the general population. Finally, it is also possible that the cancer and the blood clot share common causes or risk factors.

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Is routine extensive screening for cancer appropriate?
Given the higher than expected incidence of cancer in patients with unexplained blood clots, how far should physicians go in attempting to look for and diagnose cancer in these patients?

There continues to be debate about whether all patients with unexplained blood clots should undergo extensive screening for cancer. A wide range of diagnostic tests could potentially be performed. These include blood tests for biochemical markers that suggest cancer, ultrasound and computerized tomography (CT) of the abdomen and pelvis, upper and lower endoscopy (a very small camera in a tube used to investigate the stomach or bowel), stool and sputum examination, mammography (a special X-ray of the breast) and cervical smears in women, and ultrasound examination of the prostate in men.

Although it may appear to make obvious sense to do all we can to test for cancer, there are good reasons why this may not be a good idea, and the current evidence indeed suggests that routine extensive screening is not appropriate.

To date, only 1 study has been performed comparing the effects of extensive screening versus the effects of not screening.  Importantly, this study was not able to demonstrate conclusively that earlier diagnosis of cancer as a result of extensive screening of patients prolonged life. In addition, almost all tests-particularly invasive tests like many of those listed above-carry some risks. Patients would also have to deal with the psychological burden associated with undergoing such testing and waiting for the results. Finally, the relatively high costs of extensive testing must be taken into account.

It is also worth noting that accurate and reliable tests appropriate for a screening program are currently not readily available for the cancers most strongly associated with unexplained blood clots (cancers of the pancreas, ovary, liver, and brain).

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What tests should be performed?
In the absence of conclusive evidence to support routine extensive screening, what is the most appropriate course of action for checking for cancer? One study found that a relatively simple yet thorough clinical evaluation—including taking a detailed medical history of the patient, physical examination, basic laboratory tests, and a chest X-ray-identified abnormalities in the majority of patients with unexplained clots who were subsequently found to have cancer.

It is advisable for standard screening tests of proven effectiveness to be performed if they have not already recently been performed for another reason, for example as part of a regular screening program. These would include mammography and cervical smear (Pap) tests in women, and prostate screening in men.

If all tests are negative, implying no cancer is detected, then it has been recommended that the basic clinical evaluation is repeated every 6 months in the 2 years after the clot occurred. In this way, it is likely that most cancers, if they occur, will be promptly detected.

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Summary
  • People who develop a blood clot for which there is no apparent cause are more likely to develop cancer in the short term, compared with the general population.  Because of this fact, physicians will perform tests to look for cancer in these patients.

  • There is not yet sufficient evidence to justify extensive testing for all patients after a blood clot. Until it can be shown to prolong life a comprehensive battery of tests will probably not be performed.

  • A simple but thorough clinical evaluation (including medical history of the patient, physical examination, basic laboratory tests, and a chest X-ray), repeated at intervals and supported, if appropriate, by specific screening tests of proven effectiveness, has been recommended as a more appropriate approach.

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References
Baron JA, et al. Venous thromboembolism and cancer. Lancet 1998;volume 351:pages 1077-80.

Cornuz J. et al. Importance of findings on the initial evaluation for cancer in patients with symptomatic idiopathic deep venous thrombosis. Annals of Internal Medicine 1996;volume 125:pages 785-93.

Lee AY. Screening for occult cancer in patients with idiopathic venous thromboembolism: no. Journal of Thrombosis and Haemostasis 2003;volume 1:pages 2273-4.

Piccioli A, et al. Extensive screening for occult malignant disease in idiopathic venous thromboembolism: a prospective randomised clinical trial. Journal of Thrombosis and Haemostasis 2004;volume 2:pages 884-9.

Prandoni P, et al. Deep-vein thrombosis and the incidence of subsequent symptomatic cancer. New England Journal of Medicine 1992;volume 327:pages 1128-33.

Sørensen HT, et al. The risk of a diagnosis of cancer after primary deep vein thrombosis or pulmonary embolism. New England Journal of Medicine 1998;volume 338:pages 1169-73.

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