Warfarin Institute of America
DEDICATED TO YOUR HEALTH SINCE 2000
Is deep vein thrombosis a possible indicator of undiscovered cancer?
Courtney Frisch, Pharm D. Candidate
There has been a well known link between deep vein thrombosis (DVT) and cancer for over 150 years. The first physician to suggest this association in 1865 was Armand Trousseau.1 His story is interesting because he himself later developed a DVT and was then diagnosed with stomach cancer within a year.1 The link between DVT and cancer has been under investigation since.
Cancer patients are generally at a greater risk of developing thromboses or clots in the blood. One study showed that cancer patients were 4 times more likely to develop blood clots than the general population without cancer.2 That risk is increased to six and a half times more likely for patients who are being treated with chemotherapeutic agents.2 More recently it has been observed that some cancers seem to present soon after a recent episode of deep vein thrombosis. Several investigations have since been underway to determine the likelihood that a DVT may be the first manifestation of a previously undiscovered malignancy or cancer.
Deep vein thrombosis includes any clot of the large veins of the arms or more commonly the legs. These veins carry blood back to the heart and lungs and may carry a clot to these organs if one was formed within these veins. A clot carried through the heart to the lungs could potentially cause serious harm or be fatal. A DVT can usually be linked to an underlying cause or risk factor. Clots that have a likely cause are described as “explained” or “provoked” and are less commonly associated with cancer.1-3 Common risk factors that can provoke or cause a DVT include a surgery, trauma, childbirth, prolonged hospitalization or decreased activity within the past three months, previous history of DVT, cancer, lupus, use of oral contraceptives or a genetic predisposition to have clotting disorders.1
A clot that cannot be explained by one of the above reasons and that cannot be associated with some other cause is described as “unexplained,” “unprovoked” or “idiopathic.” These types of clots are also more commonly associated with cancer, and possibly even more commonly with metastatic cancer—or cancer that has already spread to other parts of the body and is usually harder to treat and cure.1-3 Recent studies have suggested that a person with one of these unexplained clots who has not been diagnosed with cancer may be more likely to actually have a cancer that has not yet been found and diagnosed, or an “occult” cancer.1-3
Two recent studies have been undertaken to look at the rates of the association between DVT and undiagnosed cancer. One study watched patients with a newly diagnosed DVT for six months to see if they would be diagnosed with cancer within that time. It was then compared whether these cancers were in patients with explained or unexplained DVT. About 42% of the DVTs in this study were unexplained, and about 7% of the patients with unexplained DVTs were diagnosed with cancer within the six months following diagnosis of their DVT.1 It is also significant to note that a little more than half of these cancers were diagnosed within 16 days of DVT diagnosis.1 A second, larger study looked back at the records of patients with several common types of cancer to see if an unprovoked DVT had occurred within the year prior to cancer diagnosis. In this study 0.11% of all cancer cases were associated with a diagnosis of unprovoked DVT.3 That equates to 1 of every 1000 cases of these common cancers. As in the previous study, the majority of the DVTs occurred closer to the date of cancer diagnosis—they occurred within the 4 months prior to cancer diagnosis in this study.3 In both studies many cancers were diagnosed during the same hospitalization as the DVT.1,3 This close relationship in time between occurrence of DVT and diagnosis of cancer may suggest that the DVT could possibly be a first manifestation of cancer.1,3 This conclusion may be a likely scenario considering that cancer is often associated with clotting complications.
These studies, and several others, have also helped to shed light on which types of cancers may be more commonly associated with DVTs. Some of the cancers in which this association has been observed include stomach, renal, ovarian, lung, brain, pancreatic, prostate, liver, gallbladder, colon, breast and cervical.1,3 Some of these cancers are difficult to diagnose because they have vague symptomology that may be associated with many other problems before they would be associated with cancer, that may not seem alarming until the cancer has greatly progressed, and these cancers often lack reliable routine screening tools that are able to find the cancers soon enough to improve the outcome in patients.1,3 Since many of these cancers are difficult to diagnose until later stages, they are often already in a metastatic stage upon discovery.1,3 This relationship was demonstrated in the studies mentioned above as a significant number of DVTs were also associated with cancers that were already in a metastatic stage when they were diagnosed within the six to twelve months following diagnosis of unprovoked DVT.1,3
Another important issue that the preliminary information from these studies begins to address is whether or not there will be benefit from extensive screening for cancer in individuals upon diagnosis with an unprovoked DVT. Many patients do have some abnormal clinical findings at the time of the DVT that may suggest the presence of undiagnosed cancer upon presentation with a DVT.1,3 It has been suggested that a simple clinical evaluation including a comprehensive medical history, physical examination with basic blood tests, a pelvic exam in females and a chest x-ray in smokers may be effective at detecting up to 90% of underlying cancers upon presentation with unprovoked DVT.2 This staggering number illustrates the theory that many of these unprovoked DVTs are caused by the state of cancer already existing in the body though undetected. Preliminary data also seems to suggest that extensive screening for cancer, including imaging techniques such as MRIs and CT scans, upon presentation with an unprovoked DVT may not provide extra benefit. This lack in extra benefit is likely due to the large number of cancers that may be found with simple examination and also because the majority of the cancers discovered subsequently to DVT are already metastatic. Unfortunately, finding the cancers by this point does not really seem to lead to improved outcomes or survival for the patients.1,3
Studies so far have begun to confirm that there is a likely relationship between an unexplained DVT and possible subsequent diagnosis of cancer. Most of these subsequent cancers, if they exist, are discovered within the first few months following the episode of unprovoked DVT suggesting the cancer may have already existed at the time the DVT occurred. Many of these cancers also seem to be at a very advanced metastatic stage upon their discovery. Despite these findings it is important to note that not all unprovoked DVTs imply the existence or imminent presentation of cancer as these studies showed that 7% of these patients or less were diagnosed with cancer soon after their DVT. Though this number seems small it is significant and warrants further research into the questions of what types of cancer may be more commonly associated with unprovoked DVT and what type of screening patients with an unprovoked DVT should undergo to determine if the DVT may actually be a manifestation of an undiscovered cancer.
References:
1) Hettiarachchi RJ, Lok J, Prins MH, Buller HR, and Prandoni P. Undiagnosed Malignancy in Patients with Deep Vein Thrombosis, Incidence, Risk Indicators, and Diagnosis. Cancer. 1998;1:180-185.
2) Lee AY and Levine MN. Venous Thromboembolism and Cancer: Risks and Outcomes. Circulation. 2003;107:I-17—I-21.
3) White RH, Chew HK, Zhou H, Parikh-Patel A, Harris D, Harvey D and Wun T. Incidence of Venous Thromboembolism in the Year Before Diagnosis of Cancer in 528 693 Adults. Archives of Internal Medicine. 2005;165:1782-1787.
©2005 Courtney Frisch
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