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Good & Bad News about Prophylactic Thrombolysis in Cancer Patients

Samson, Kurt

doi: 10.1097/01.COT.0000453659.89424.3f


Although hospitalized cancer patients receive anticoagulants to prevent venous thromboembolism (VTE) much more often than has been reported in the past, a new study shows that therapy is often prescribed without adherence to published recommendations on risk factors or by carefully assessing risk on a per-patient basis.

The prospective, multicenter, cross-sectional study (JCO 2014;32:1792-1796), assessed cancer patients admitted at hospitals for various procedures and found that more than 70 percent of individuals without contraindications received therapy. However, the hospitals in general did not follow published risk-evaluation guidelines in selecting which patients to treat—notably those by the American College of Chest Physicians (ACCP) and the American Society for Clinical Oncology.

The team, led by Jeffrey I. Zwicker, MD, Director of Benign Hematology Clinical Research at Beth Israel Deaconess Medical Center and Assistant Professor at Harvard Medical School, also examined factors that influenced the use of the therapy by hospitals. Until now, the reported rates of pharmacologic thromboprophylaxis have been especially low for cancer patients, ranging from 18 percent to 56 percent. But these past studies have relied on retrospective analysis of treatment records culled from large databases, he noted in an interview.



In one analysis of some 2.5 million U.S. hospital discharges, cancer patients had the lowest rates of thromboprophylaxis compared with other major medical conditions, including acute myocardial infarction, ischemic stroke, heart failure, and severe lung disease.

The Zwicker et al trial, by the North America Cancer and Thrombosis Study Group, prospectively reviewed therapy at five academic hospitals that treated 775 cancer patients admitted for different reasons. Among the patients, 31.9 percent had relative contraindications to prophylaxis and were not treated. Among the other 528 patients, the rate was 74.2 percent, and ranged from 70.4 to 78.0 percent.

However, 63 percent of treated patients were classified as low risk for thrombosis based on the Padua Scoring System, while among 136 patients who did not receive prophylactic anticoagulation, 59 percent were considered high risk by the rating system.

Among those without contraindications, patients with nonhematologic malignancies were significantly more likely to receive treatment than those with hematologic malignancies were, and patients admitted for cancer therapy were significantly less likely to receive such preventive therapy than those admitted for other reasons.

The most common factor influencing administration was a history of VTE, blood or non-blood cancers, as well as acute infection or rheumatologic disorder, trauma, or surgery within the prior six months.

“Because retrospective analyses of large databases in earlier published studies reported much lower rates, we were surprised to find that so many cancer patients are receiving treatment. We thought it would be underutilized,” he said.

“However it appears to be commonly prescribed without regard to the presence or absence of concomitant risk factors. For example, despite an increased risk of thrombosis associated with chemotherapy, it was surprising to see that these patients were less likely to receive pharmacologic thromboprophylaxis.”

There is now almost a reflex tendency for hospitals to give anticoagulation therapy to cancer patient unless it is clearly contraindicated, he said. “But the rhyme and reason for current practices is not based on strong data.”

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Editorial: Oncologists Need to Take Action

In an accompanying editorial (JCO 2014;32:1754-1756), Agnes Y. Lee, MD, Medical Director of the Thrombosis Program and Associate Professor of Medicine at the University of British Columbia, wrote that it is time for clarification on how best to identify and treat patients at risk of VTE prophylaxis and how to ensure they are treated with appropriate anticoagulant therapy.

“Considering that 60 percent of venous thromboembolism cases are related to hospitalization and that 20 percent of VTE occurs in oncology patients and that VTE is associated with increased in-hospital mortality, it is disheartening that good-quality research has not been done to address in-hospital thromboprophylaxis in patients with cancer,” she said. “The lack of evidence to guide best practice in this everyday clinical setting is unacceptable. Dr. Zwicker and the other researchers have sounded an alarm. The oncology community needs to take action.”



Although individual risk factors associated with thrombosis are well established, validated risk-assessment tools for estimating the overall risk of thrombosis in hospitalized cancer patients remain unavailable, she said.

And while the current study underscores the importance of better screening and treatment, the Padua Prediction Score used in the study, which is also recommended by the ACCP, has not undergone rigorous external validation.

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‘One Size Does Not Fit All’

Asked for his opinion for this article, Gary H. Lyman, MD, Co-director of the Hutchinson Institute for Cancer Outcomes Research at Fred Hutchinson Cancer Research Center, who helped develop ASCO's 2007 guidelines on pharmacologic thromboprophylaxis as well as the subsequent update in 2013 (JCO 2013:31:2189-2204), said, “It is important to remember that cancer patients are a very heterogeneous group, and these patients are undergoing many different types of procedures.”

The ASCO guidelines were developed from data from randomized clinical trials on the prevention of VTE in hospitalized medical and surgical cancer patients as well as ambulatory patients receiving cancer therapy. In addition, recommendations included data on immediate and extended secondary prophylaxis in patients with established VTE, and many subgroups of cancer patients were not well represented in these, he noted.

“We extrapolated our recommendations from general findings in seriously ill patients with many other problems. The real challenge is to make sure that the best data is available for hospitals and treating physicians. Low molecular weight heparin has been used for years to prevent VTE, but newer drugs are being developed that might help patients who suffer VTE despite heparin.”

For hospitals, he said, it is clear that prophylaxis is reasonable in most cancer patients and should be considered.

“It is less arbitrary than other treatments, but we have always been uncomfortable with making general statements, because with such a wide mix of patients, one size clearly does not fit all. This paper points out that clinicians do not do a very good job selecting which patients to treat. While two-thirds of patients did receive anticoagulant therapy, one quarter to one third who might have been at risk did not.”



The take-home message, he said, is the need to evaluate each patient's uniqueness, not just for VTE but also for other patient factors: “I think we need to improve personalized patient risk assessment. We can do better as oncologists, but we also need more data on which to base our decisions.”

Lyman said the ASCO guidelines are currently being implemented in an indiscriminate fashion, because hospitals feel they have no choice but to treat or not treat patients in accordance with the guidelines without awareness of the fact that they are not meant to replace individual assessment on a per-patient basis. In one study conducted in Boston, after hospitals adopted built-in directives to administer therapy prophylaxis rates went up exponentially, he noted.

“We also know that if we make these recommendations too complicated, treatment will be withheld from more patients. There is a perception at hospitals that if you want to improve prophylaxis in high-risk patients you have to have a standing order to treat all of them—hospitals do not want to get dinged by the Joint Commission.

“But hospital administrators and regulators need to get a little more advanced with regard to the need for assessing risk on a personal level for each patient, which is something that the authors of this new paper call for.”

© 2014 by Lippincott Williams & Wilkins, Inc.
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