DVT and Pulmonary Embolism with Low- Molecular-Weight Heparin

Abstract & Commentary

Synopsis: In a tertiary care hospital, the use of nurses to either teach patients to inject or directly administer the low-molecular-weight heparin dalteparin (200 U/kg every 24 hours) for a minimum of five days resulted in 95% completion (194 patients) of home treatment for deep venous thrombosis or pulmonary embolism. Recurrent thromboembolism occurred in less than 4% and major hemorrhage occurred in 2%.

Source: Wells PS, et al. Arch Intern Med 1998;158: 1809-1812.

Pulmonary thromboembolism is a common and potentially deadly illness. There is an estimated incidence as high as 5% in the general population with a mortality of at least 20,000 individuals per year in the United States. Until now, the management paradigm has involved admission of patients to receive intravenous heparin once the diagnosis of either deep venous thrombosis or pulmonary embolism had been made. Hospital stay has been generally 7-10 days after a switch to warfarin had been successfully made. Prolonged hospitalization was often the result of inability to establish appropriate dosing levels using partial thromboplastin time (PTT) for standard heparin therapy and the prothrombin time (PT) or, more recently, the International Normalized Ratio (INR) for warfarin. Low-molecular-weight heparin has greater activity against factor Xa than standard heparin resulting in less risk of hemorrhage. Prolonged bioavailability and longer half-life allow a more predictable response with once or twice daily subcutaneous injections without the need for laboratory monitoring. In several recent trials, the use of low-molecular-weight heparins resulted in outcomes similar to unfractionated heparin for prevention of venous thrombosis and treatment of pulmonary embolism.1,2 This ability to be administered subcutaneously has raised the possibility that home treatment would be possible. In recent studies,3,4 outpatient treatment was demonstrated to be safe and effective for deep venous thrombosis using low-molecular-weight heparin administered subcutaneously. The study of Wells and colleagues builds on this information by evaluating this modality outside a research setting. Low-molecular-weight heparin was given using two methodologies of care. In one, community-based homecare nurses gave the patients injections and in the second, patients learned to inject themselves under nurse supervision during the three months of treatment. Patients had objective evidence by ultrasonography or venography of deep venous thrombosis or pulmonary embolism. Exclusion criteria included the need for hospitalization due to other factors (i.e., active bleeding, inpatient status, hemodynamic instability, requirement for pain medication, or age younger than 18 years). Patients were given 200 U/kg of dalteparin for a minimum of five days or until the patient’s INR was greater than 2.0 for at least two days on warfarin. A total of 194 patients over 10 months were studied with more than 95% receiving their entire treatment at home. Approximately one-half of the patients injected themselves and the others received injection by the homecare nurse. The average age was approximately 64 years. Thirty-four patients had pulmonary embolism and cancer was present in approximately one-third of patients. There was no significant difference in the rate of recurrence between nurse-injected (3.2%) or self-injected patients (4%). Overall recurrence rate was 3.6%. Also, there were no significant differences in the rates of major hemorrhage, minor hemorrhage, or death. Eleven deaths were due to metastatic cancer.

Table 
Complications of Outpatient Treatment 
Overall(%) 
Bleeding
3.6
Minor
5
Major
7
Death
7
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Comment by Alan m. fein, MD

The use of anticoagulation to treat thromboembolic disease is an important therapeutic modality but is also a major cause of morbidity and mortality in and out of the hospital. Heparin is among the major causes of drug-related complications in hospitalized patients, while the increased use of warfarin continues to result in major morbidity and mortality (in some studies up to 10% per year)—especially in older patients and those with malignancy. Therefore, the use of low-molecular-weight heparin that permits anticoagulation without the need for continued monitoring is a welcome addition to the therapeutic armamentarium. Several previous studies have demonstrated outpatient therapy with low-molecular-weight heparin to be safe with similar outcomes and complications to inpatient therapy. In this outcome study performed in a community setting, it was demonstrated that more than 80% of all patients could be treated at home using either self-injection or nurse supervised injection. In previous studies, 30-75% of patients with venous thromboembolism were excluded because of potential complications. Combining the results of both methods of treatment, overall rates of recurrence were low (less than 4%) and bleeding and death were similarly low (2% and 7%, respectively). Since none of the deaths occurred during the first two weeks of the study, it seems unlikely that these patients died of pulmonary embolism. Despite the overall positive results, the application of low-molecular-weight heparin therapy should be introduced cautiously to outpatients. As Wells et al point out, patients with hemodynamic instability or risk of bleeding were excluded. Based on my own practice, a much lower percentage than the 80% reported would have been able to be treated at home. My own comfort level with home treatment would need to be higher than it is currently to apply this to a broad range of patients. Still, the use of low-molecular-weight heparin for outpatient treatment of venous thrombosis and pulmonary embolism should satisfy the need to reduce cost of care and improve patient satisfaction and needs to be further explored.

References

1. The Columbus Investigators. N Engl J Med 1997; 337:657-662.

2. Simonneau G, et al. N Engl J Med 1997;337:663-669.

3. Koopman MMW, et al. N Engl J Med 1996;334:682-687.

4. Levine M, et al. N Engl J Med 1996;334:677-681.