Thromboprophylaxis in Cancer Patients: Needs Rethink

Janis C. Kelly

May 08, 2014

A new multicenter study in the United States has found that use of thromboprophylaxis in hospitalized cancer patients is now much higher (74%) than has been previously reported, but it also found that many of these patients were at low risk, and about a third of the patients receiving anticoagulation had contraindications.

The findings were published online May 5 in the Journal of Clinical Oncology. The authors, headed by Jeffrey I. Zwicker, MD, assistant professor of medicine at Harvard Medical School and the Beth Israel Deaconess Medical Center, Boston, Massachusetts, conclude that "current standard practice requires attention."

An accompanying editorial calls out for action. Agnes Y. Y. Lee, MD, PhD, from the University of British Columbia Thrombosis Program, Vancouver, Canada, writes: "Considering that 60% of venous thromboembolism cases are related to hospitalization, that 20% of venous thromboembolism occur in oncology patients, and that venous thromboembolism 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.

"The lack of evidence to guide best practice in this everyday clinical situation is unacceptable," she writes. "Zwicker et al have sounded an alarm. The oncology community needs to take action."

The oncology community needs to take action. Dr. Agnes Lee

Current clinical practice guidelines call for routine pharmacologic thromboprophylaxis to reduce the elevated risk for venous thromboembolic events (VTEs) in hospitalized cancer patients. Previous studies, including retrospective medical record reviews, have shown lower rates of thromboprophylaxis in cancer patients (around 18% to 56%).

The new study, a prospective, cross-sectional study involving 775 patients with cancer hospitalized in 5 academic medical centers, found that thromboprophylaxis was used in 74% of patients, and 50.6% received pharmacologic thromboprophylaxis. Unfractionated heparin was ordered in 62.0% of uses (given tid in 94% of patients), enoxaparin in 37.8%.

"I was expecting the rate of thromboprophylaxis to be lower, more in line with prior studies," Dr. Zwicker told Medscape Medical News.

However, 63% of these cancer patients were classified as being at low risk for VTE.

In addition, 31.9% had contraindications to anticoagulation (most commonly, thrombocytopenia). Unfractionated heparin was ordered in 62.0% of uses (given tid in 94% of patients), enoxaparin in 37.8%.

Cancer patients without contraindications to anticoagulation were significantly more likely to receive thromboprophylaxis if they were hospitalized with nonhematologic malignancies but less likely to receive thromboprophylaxis if they were admitted for cancer therapy (radiation or chemotherapy) or had central venous catheters. Multivariable logistic regression showed that the strongest predictor of pharmacologic prophylaxis was a prior history of VTE.

However, the researchers found that decisions to administer pharmacologic thromboprophylaxis had often been made without consideration of the presence or absence of risk factors for VTE. Risk was classified by a Padua Prediction Score of ≥4, according to which 63% of cancer patients at low risk for VTE received anticoagulation and 58.8% who were at high risk for VTE did not. High Padua Predictive Score was not independently associated with increased odds of receiving thromboprophylaxis.

Dr. Zwicker said, "Since there is a strong association between cancer and thrombosis, physicians have a lower threshold to rule out thrombosis. Increasing numbers of incidental VTE are being diagnosed with staging imaging. When we previously conducted an outpatient thromboprophylaxis trial, a surprising number of large burden DVT [deep venous thrombosis] were picked up on routine ultrasounds. Whether such routine imaging would be useful to assess for existing DVT in hospitalized cancer patients has not been established."

The authors suggested that the difference between the 74% thromboprophylaxis rate they observed among cancer patients considered eligible for anticoagulation and the 18% to 56% rates reported by others might be partly due to differences in prospective vs retrospective data collection.

"Cancer patients with metastatic disease and additional risk factors such as immobility or infection should receive thromboprophylaxis. Patients clearly at increased risk for hemorrhage should not receive thromboprophylaxis," Dr. Zwicker emphasized.

The authors noted that all participating sites were academic medical centers, so whether the data are applicable to community hospitals is not known.

Clinicians should be mindful that pharmacologic thromboprophylaxis is indeed a medication with potential side effects. Data support benefit only in patients with thromboembolic risk factors and suggest that its use be in accordance with data and recommendations generated by societies such as the American Society of Clinical Oncology and the American College of Clinical Pharmacology, Dr. Zwicker said.

The authors concluded, "On the basis of the results of this study, it is apparent that the majority of patients with cancer admitted to these five academic medical centers in the United States receive pharmacologic thromboprophylaxis. However, in the quest for strict compliance with federal mandates and competency measures and for minimizing legal liabilities, the lack of evidence supporting a one-size-fits-all approach to thromboprophylaxis for inpatients with cancer has been overlooked."

"These data bring into focus the deficiencies in both current clinical practice and evidence. There are little data to suggest that patients with a lower risk of cancer benefit from routine thromboprophylaxis," they add.

In the editorial, Dr. Lee notes that there are no validated risk assessment tools for estimating thrombosis risk in hospitalized cancer patients and that the Padua Prediction Score does not include risk factors unique to patients with cancer, such as presence of metastatic disease or use of chemotherapy.

Dr. Lee also said that some nonadherence with thromboprophylaxis prescription might be due to the "lack of an easy, cheap, painless anticoagulant prophylaxis option" as an alternative to unfractionated heparin injections twice or 3 times a day.

Dr. Zwicker reported research funding from sanofi-aventis. Other coauthors reported consulting fees, honoraria, or research funding from Daiichi-Sankyo, Boehringer Ingelheim, Janssen Pharmaceuticals, Pfizer, sanofi-aventis, LEO Pharma, Bristol-Myers Squibb, and Portola Pharmaceuticals. Dr. Lee reported no relevant financial relationships.

J Clin Oncol. Published online May 5, 2014. Abstract, Editorial


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