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Weighing the evidence: LMWH in embolism.

The Patient

A 34-year-old female with advanced multiple sclerosis presents with a 14-hour history of abdominal pain behaviors and tachypnea. A CT scan shows bilateral pulmonary emboli with evidence of a "D-shaped" left ventricle consistent with right ventricle pressure/volume overload. She is placed on unfractionated heparin, but her family is concerned because blood draws every 4 hours are distressing. They are desperate for another way for her to receive heparin. Low-molecular-weight heparin is a possibility, but the evidence for LMWH in symptomatic pulmonary embolism to prevent further PEs needs to be checked.

The Question

In patients with symptomatic PEs, is LMWH as efficacious as unfractionated heparin for preventing recurrent PEs?

The Search

Using PubMed ( we entered "low molecular weight heparin and pulmonary embolism" and employed the limit "meta-analysis."

Our Critique

This is a well-conducted systematic review of the literature that included studies assessing the use of LMWH for nonmassive symptomatic pulmonary embolism. Search terms seemed appropriate and complete, but only three databases were searched. Sensitivity analyses were performed and the results are robust to exclusion of individual studies. No publication bias was detected. By the authors' own admission, the metaanalysis is limited by a lack of outcomes, so stable estimates cannot be provided for the odds ratios.

Clinical Decision

The patient is placed on once-daily LMWH. The family is pleased, and her physician is pleased because the activated partial thromboplastin time no longer needs to be monitored. The bias has always been that turning off the heparin when patients are over-anticoagulated with unfractionated heparin exposes them to periods in which they are not antico-agulated. The patient is dismissed from the hospital on LMWH and coumadin.


D.J. Quinlan et al.

Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a metaanalysis of randomized, controlled trials (Ann. Intern. Med. 140[3]:175-83, 2004).

* Criteria for study inclusion: All published and unpublished randomized trials compared fixed-dose LMWH with dose-adjusted intravenous unfractionated heparin for the initial treatment of pulmonary embolism (PE). Studies had to be randomized and had to include patients with objectively diagnosed symptomatic PE or asymptomatic PE with symptomatic deep vein thrombosis (DVT). Studies had to compare fixed-dose LMWH with dose-adjusted intravenous unfractionated heparin and use objective methods to assess one or more clinical outcomes.

* Study identification: Medline, Embase, and the Cochrane Library were searched through Aug. 1, 2003. Bibliographies of journal articles and abstracts from major international meetings were reviewed, and manufacturers of LMWH were contacted to learn of unpublished studies.

* Study selection: Two investigators independently reviewed studies for inclusion. Standard study quality was employed and disagreements were resolved by consensus. Studies were excluded for the following reasons: LMWH was administered intravenously, LMWH dosing was adjusted according to laboratory values, unfractionated heparin was administered subcutaneously, duration of treatment was unequal, or objective diagnostic testing was not done to screen for asymptomatic PE.

* Data extraction: Two investigators independently extracted data on study design, study quality, and 3-month efficacy and safety for symptomatic venous thromboembolism (VTE), death, major bleeding, and minor bleeding. Data were confirmed by reviewer consensus.

* Results: Of 551 potentially eligible citations, 12 studies with 1.951 patients were included. LMWH preparations evaluated were certoparin, dalteparin, enoxaparin, nadroparin, reviparin, and tinzaparin. LMWH or unfractionated heparin was continued for a mean of 5-14 days, with follow-up at least 3 months. At the end of treatment, the odds ratio was 0.63 (95% confidence interval: 0.33-1.18) for symptomatic VTE, 0.47 (95% CI: 0.17-1.26) for recurrent DVT, and 0.91 (95% CI: 0.45-1.85) for recurrent pulmonary embolism favoring LMWH. The odds ratio for all-cause mortality was 1.20 (95% CI: 0.59-2.45) favoring unfractionated heparin, but the confidence interval is wide. No statistically significant differences were observed between LMWH and unfractionated heparin for recurrent DVT and death at 3 months, although all point estimates favored LMWH. The odds ratio for major bleeding was 0.67 (95% CI: 0.36-1.27) and for minor bleeding was 1.08 (95% CI: 0.73-1.59), both of which favored LMWH. No study heterogeneity was detected for symptomatic VTE at end of treatment and at 3 months.


DR. JON O. EBBERT and DR. ERIC G. TANGALOS are with the Mayo Clinic in Rochester, Minn. To respond to this column or suggest topics for consideration, write to Dr. Ebbert and Dr. Tangalos at our editorial offices or
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Title Annotation:Mindful Practice
Author:Ebbert, Jon O.; Tangalos, Eric G.
Publication:Internal Medicine News
Date:Apr 15, 2004
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