Most patients who develop venous thromboembolisms (VTE) while being treated for cancer, do so as outpatients, according to results of a retrospective, observational study comparing the incidence of VTE among inpatients and outpatients with cancer. Yet many outpatients do not even realize that they are a risk for venous thromboembolism, noted the study’s lead investigator, Alok Khorana, MD, Associate Professor of Medicine and Vice-Chief, Division of Hematology/Oncology, James P. Wilmot Cancer Center, University of Rochester Medical Center in Rochester, New York. By educating patients about the risks of venous thromboembolism and encouraging them to alert their treatment team if signs or symptoms develop, physicians can help reduce related morbidity and even mortality, while answering the Surgeon General’s Call to Action to reduce the public health burden of VTEs.

Of the 17,784 patients with cancer identified using a linked database, 996 (5.6%) developed blood clots. A much higher proportion of venous thromboembolism was diagnosed in outpatients than in inpatients (78.3% vs 21.7%). The results were presented in abstract form at the American Society of Hematology 2011 Annual Meeting. Dr. Khorana and his research team are now working on the full study report, which they hope to complete in mid-2012 and submit for publication.

Life-threatening Complication

“It’s really important to make sure patients are aware that VTE is a problem,” Dr. Khorana said. “Right now, most patients don’t even understand that this is a complication that they could develop. And it’s a life-threatening complication. About 1 in 10 patients with cancer will die of a venous or arterial blood clot.”

Acknowledging that physicians are doing a good job educating patients about other possible complications of treatment, such as nausea, vomiting, infections, and fever, Dr. Khorana said that venous thromboembolism also needs “to enter the discussion and be more firmly rooted in the patient education program.” This should include the risk of VTE, the warning signs and symptoms, and “when to call us if any of those signs or symptoms occur,” he explained (see sidebar, Expect Questions from Your Patients).

The risk factors for blood clots among outpatients appear to differ from those among inpatients, Dr. Khorana said. “Typically, we thought our inpatients—who were sicker, less mobile, and laying in bed all the time—were more susceptible to blood clots. But the patients I typically see in the clinic who get blood clots are just as active as the rest of my patients with cancer,” Dr. Khorana noted.

“It is a whole different set of risk factors,” he continued. “Certain patients with cancer are much more likely to get clots, regardless of their mobility. We think it’s really a combination of the type of cancer and the types of chemotherapy and other systemic therapeutics that we are using.” These include agents like thalidomide (Thalomid), lenalidomide (Revlimid), and bevacizumab (Avastin), Dr. Khorana said. In addition, the study identified the use of doxorubicin as a significant predictor of venous thromboembolism.

Patients whose primary site of cancer is the stomach, pancreas, brain, or testicles were shown by the study to be at higher risk of developing VTE. In an interview with The ASCO Post, Dr. Khorana said that there is also an increased risk of venous thromboembolism among patients with hematologic malignancies.

“We typically think of blood clots as occurring in patients with solid tumors, but patients with hematologic malignancies, especially lymphoma and myeloma, also have a high rate of clots,” Dr. Khorana noted. “Patients with cancer who develop blood clots are more likely to get another one,” he added.

The study also identified a history of pulmonary disease as a predictor of venous thromboembolism. “Patients who have other medical problems are more likely to get clots, and that includes lung disease, for example, having chronic obstructive pulmonary disease, emphysema, or asthma. Those types of pulmonary illnesses increase the risk, not just for pulmonary embolism, but for any clot,” Dr. Khorana said.

Prophylaxis Not Recommended

Patients who have signs and symptoms of venous thromboembolism, such as swelling in one leg, a sudden onset of chest pain, or shortness of breath, should be encouraged to report and discuss these symptoms with a member of their cancer treatment team as soon as possible, Dr. Khorana advised.

Most patients who develop these symptoms as outpatients will not be receiving anticoagulants. “And it is not clear that everybody should,” Dr. Khorana said. “Although patients with cancer are at high risk, the risk is unevenly distributed. Certain types of cancer have much higher risk than others, but for head and neck cancer and breast cancer, for instance, the risk is pretty low.”

“At this point, none of the guidelines are recommending outpatient prophylaxis,” Dr. Khorana said. This could change, however, depending on the results of “two or three very large studies that were just completed,” he added (see sidebar, Clinical Trials of VTE Prophylaxis for Outpatients). The exception for now would be patients with myeloma. “Almost all myeloma patients will receive some form of prophylaxis, such as aspirin, warfarin, or low-molecular-weight heparin. But beyond that, for the larger cancer population, there is no specific recommendation for prophylaxis just yet.”

Dr. Khorana, who was a member of the panel that developed the ASCO recommendations for VTE prophylaxis and treatment in patients with cancer, said the panel “did look at outpatient VTE, but at that time there were no data to support a recommendation. We are in the process of updating our guidelines, and we hope to have an updated version out by the middle of 2012,” he said. The new studies about venous thromboembolism are among the triggers that prompted the ASCO panel to update the guidelines.

Meeting the Public Health Challenge

The findings about the prevalence of VTE among cancer outpatients have important public health implications, Dr. Khorana said, “because right now, the Joint Commission, regulatory authorities, and the Surgeon General, are stressing that we need to reduce the public health burden of VTE. But the only prophylaxis that occurs is in the inpatient setting. So if nearly 80% of clots are occurring in the outpatient setting, even if you achieve 100% compliance with prophylaxis in the inpatient setting, you are not going to prevent up to 80% of the clots.”

To test the hypothesis that earlier hospital discharge might mean that patients are being sent home with a blood clot that started in the hospital and was later diagnosed in the outpatient setting, the investigators looked at how many outpatients diagnosed with venous thromboembolism had been in the hospital in the preceding 30 days. “It turned out about 20% were,” Dr. Khorana said. “So there is some linkage to hospitalization. But again, 80% were not in a hospital within the past 30 days, so it is still primarily an outpatient diagnosis.”

The study also found that venous thromboembolism was an independent predictor of higher hospital costs. Total mean annual hospital costs were more than twice as high for those with VTE ($22,917) than for those who did not have VTE ($11,250). ■

Disclosure: Dr. Khorana is a consultant for and receives cancer-related research funding from several drug companies, including Roche/Genentech, Eisai, Johnson & Johnson, Boehringer Ingelheim, LEO Pharma, sanofi-aventis, Bayer, Bristol-Myers Squibb, and Daiichi-Sankyo. Sanofi-aventis funded this study.

SIDEBAR: Clinical Trials of VTE Prophylaxis for Outpatients

SIDEBAR: Expect Questions from Your Patients