Pulmonary embolism is the cause of approximately 10% of hospital deaths despite approved therapies for treatment and prevention. July 26, 2007

Grendel Burrell, July 26, 2007

Canada Frederick A. Spencer, M.D., McMaster University, and colleagues report data from a study of patients with an episode of venous thromboembolism in the July 23 issue of the Archives of Internal Medicine(1). Also published in the same issue, a meta-analysis of previous studies published determines that both unfractionated and low-molecular-weight heparin (LMWH) are effective in preventing venous thromboembolism (VTE) in the legs and Pulmonary Embolism (PE) in hospitalized patients. In this meta-analysis, LMWH was more effective and safer than unfractionated heparin. Additionally, unfractionated heparin administered three times daily was more effective than unfractionated heparin administered two times daily.

Patients are more likely to develop venous thromboembolism within 3 months of hospital discharge than during their hospital stay. The majority of cases of deep vein thrombosis and Pulmonary Embolism occur within three months of hospital discharge, but most patients do not receive prophylactic treatment. For at-risk patients, there are pharmacologic and non-pharmacologic options to prevent deep vein thrombosis. Yet, as many as 300,000 patients may die of Pulmonary Embolism each year in the United States alone.

In the 1897 patient records reviewed by Spencer and colleagues from three one-year periods, 1999, 2001, and 2003, 73.7% of patients (n=1,399) developed VTE as outpatients. Of the 73.7 % who developed VTE in the outpatient setting, 23.1% of these had undergone surgery, and 36.8% had been hospitalized in the preceding three months. Among those hospitalized patients, 67% experienced VTE within one month of hospitalization. 29% of patients had an active cancer, while 19.9% had a history of a blood clot.

The study’s authors ponder whether many of these cases could have been prevented by the appropriate utilization of prophylaxis with graduated compression stockings, pneumatic compression devices, or low, fixed-dose anticoagulation. 40% of the 516 patients with VTE who had recently been hospitalized received no prophylaxis while hospitalized. Among those who were prophylaxed, it was uncertain whether they received appropriate guideline-recommended prophylaxis with the correct drug, correct dose, and proper duration.

Most cases of VTE occurred within 29 days of hospital discharge, and 41 % occurred within 14 days. Half of the outpatients who experienced VTE following hospitalization had a length of stay that was four days or less. This indicates that patients hospitalized for short stays are especially vulnerable to subsequent VTE, a finding not widely recognized among health care professionals. Over the last decade, hospital stays are decreasing in length, and consequently, patients at home may be less encouraged by family to mobilize and resume activities of daily living. More discharged patients might benefit from anticoagulant therapy.

Since the study was a retrospective assessment of patient records, some patients may have visited doctors or hospitals that were not captured in the chart review. This represents a potential limitation of the study. In the same issue of the Archives of Internal Medicine, a related paper describes a meta-analysis of previously published randomized trials, all of which compared medications used to prevent VTE with each other or with a control group of patients who did not receive prophylaxis. The meta-analysis includes 36 studies (48,000 hospitalized medical patients), all published prior to June 2006. 14 studies compared unfractionated heparin with a control, 11 compared LMWH to a control, 10 compared the two heparins to each other, and 1 compared fondaparinux sodium with placebo.

Unfractionated heparin compared to control groups provided 67% lower risk of deep vein thrombosis and a 36% lower risk of PE. A dose of 5,000 units 3 times daily was more effective than 5,000 units two times daily (risk ratio [RR], 0.27; 95% CI, 0.20-0.36; versus RR, 0.52; 95% CI, 0.28-0.96). LMWH was associated with a 44% lower risk of deep vein thrombosis and 63% lower risk of PE. When LMWH was compared to unfractionated heparin, LMWH was associated with a 32% lower risk of deep vein thrombosis and a 53% lower rate of hematoma at the injection site. The authors found no difference between the two agents in the risk of bleeding or thrombocytopenia. Additionally, fondaparinux demonstrated effectiveness in the prevention of venous thromboembolism (2) Mortality was not reduced by prophylactic therapy with these drugs; yet, decreasing the incidence of VTE and [pulmonary embolism]y should substantially reduce the clinical sequelae and medical costs. However, one episode of VTE places a patient at substantially greater risk of a second episode, and 30% of patients who stop anticoagulation will have a recurrence within 10 years.

4 million surgical patients and almost 8 million medical patients warrant specific prophylaxis orders each year in the United States alone (3). The Spencer paper shows that omitting inpatient VTE prophylaxis can cause a serious spike in outpatient VTE that, until now, has been labeled as “community acquired” rather than “hospital acquired” VTE (4). Samuel Z. Goldhaber, MD, Professor of Medicine at Harvard Medical School and Director of both the Anticoagulation Service and the Venous Thromboembolism Research Group at Brigham and Women’s Hospital, told WikiDoc,  “We know that if we increase the rate of utilization of prophylaxis in and out of the hospital, we could see the rate of DVT/PE substantially reduced.” Patient risk is easily assessed, and it is important to employ strategies to determine whether high quality hospital medicine is being practiced. Ongoing assessment of the frequency with which preventive strategies against VTE are ordered in the hospital setting will soon be government mandated.

Goldhaber and colleagues are running a clinical trial of 2,500 patients at 25 institutions to determine the effectiveness “human to human alerts” by a research nurse or pharmacist to the physician about a patient’s risk of VTE. Outcome is symptomatic DVT and PE at 90 days. Data may be available in the 4th quarter, 2008. The study is sponsored by Sanofi Aventis, and is a study of physician behavior, not a study of drug therapy. Goldhaber’s group previously showed that a computerized electronic alert to physicians can lower the symptomatic VTE rate by 41% (Kucher et al, NEJM, March 10, 2005).

Who’s at risk (5)?


 * More than 38 million adults were hospitalized in 2003, at one or more 6,000 U.S. hospitals
 * Any person 18 or over who is hospitalized for major surgery, especially hip or knee surgery, and recovers in the hospital for two or more days
 * People undergoing in-hospital hip or knee surgery have a 50-percent chance of developing a blood clot
 * Any person age 40 or over who is hospitalized for more than two days for any serious medical illness, such as heart or lung disease, cancer or infection

References:


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 * 1) ref2 pmid=17646601


 * 1) ref3 pmid=17626256


 * 1) ref4 pmid=17646597


 * 1) ref5 pmid=17626254

Other on line references: North American Thrombosis Forum