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Summaries for Patients are a service provided by Annals to help patients better understand the complicated and often mystifying language of modern medicine.
SUMMARIES FOR PATIENTS
What Is the Most Effective Blood Thinner for Treating Patients with Blood Clots in the Veins?
6 May 2003 | Volume 138 Issue 9 | Page I-63
Summaries for Patients are presented for informational purposes only. These summaries are not a substitute for advice from your own medical provider. If you have questions about this material, or need medical advice about your own health or situation, please contact your physician. The summaries may be reproduced for not-for-profit educational purposes only. Any other uses must be approved by the American College of Physicians.
The summary below is from the full report titled "Suboptimal Monitoring and Dosing of Unfractionated Heparin in Comparative Studies with Low-Molecular-Weight Heparin." It is in the 6 May 2003 issue of Annals of Internal Medicine (volume 138, pages 720-723). The authors are R. Raschke, J. Hirsh, and J.R. Guidry.
What is the problem and what is known about it so far?
When blood clots form in veins (blood vessels that carry blood back to the heart), serious and even fatal complications can occur. Doctors use blood thinners to promote clot breakdown and prevent additional clots. For many years, the most commonly used blood thinner has been a drug known as unfractionated heparin. To be effective, unfractionated heparin must be injected every 6 hours (or given continuously through a needle in a vein). This requires hospitalization and careful daily monitoring of the dose to confirm effective blood thinning. More recently, another preparation of heparin, low-molecular-weight heparin (LMWH), has been introduced. It can be given at home, requires less frequent injections, and does not require daily monitoring of the dose. However, LMWH is about 10 times as expensive as unfractionated heparin. Several studies have suggested that LMWH is more effective than unfractionated heparin. Since the implications for cost and effectiveness are important, doctors need to be confident that these studies fairly compare unfractionated heparin and LMWH. The problem is that to make a fair comparison, researchers must be certain that the correct dose of unfractionated heparin was administered. This depends on accurate laboratory tests. Over the past 25 years, many different laboratory tests have been used, each having a different standard for effective blood thinning dose.
Why did the authors do this particular study?
To find out whether previous studies had carefully considered the potential influence of variations in laboratory tests in concluding that LMWH is more effective than unfractionated heparin.
How was the study done?
The researchers searched the medical literature from 1984 to 2001 to identify published articles that randomly assigned patients to receive either LMWH or unfractionated heparin and then evaluated how the researchers decided on the correct dose of unfractionated heparin.
What did the researchers find?
15 journal articles were identified. Only 3 of these articles described the specific laboratory methods used to evaluate the degree of blood thinning caused by a particular dose of unfractionated heparin, while 10 articles simply assumed that a standard evaluation of blood thinning was effective. Only 3 articles reported exactly how the dose of unfractionated heparin was adjusted.
What were the limitations of the study?
The researchers did not compare clinical outcomes between studies with and without careful attention to methods for monitoring blood thinning.
What are the implications of the study?
Although this study identifies the possibility of unfairness in previous comparisons between unfractionated heparin and LMWH, it does not prove that unfractionated heparin is as good as or better than LMWH in treating patients with blood clots in the veins.
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  J. Hirsh, K. A. Bauer, M. B. Donati, M. Gould, M. M. Samama, and J. I. Weitz Parenteral Anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 141S - 159S. [Abstract] [Full Text] [PDF]
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J. B. Segal, M. B. Streiff, L. V. Hofmann, K. Thornton, and E. B. Bass Management of Venous Thromboembolism: A Systematic Review for a Practice Guideline Ann Intern Med, February 6, 2007; 146(3): 211 - 222. [Abstract] [Full Text] [PDF]
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 V. Snow, A. Qaseem, P. Barry, E. R. Hornbake, J. E. Rodnick, T. Tobolic, B. Ireland, J. Segal, E. Bass, K. B. Weiss, et al. Management of Venous Thromboembolism: A Clinical Practice Guideline from the American College of Physicians and the American Academy of Family Physicians Ann. Fam. Med, January 1, 2007; 5(1): 74 - 80. [Abstract] [Full Text] [PDF]
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 G. R. Hetzel and C. Sucker The heparins: all a nephrologist should know Nephrol. Dial. Transplant., October 1, 2005; 20(10): 2036 - 2042. [Full Text] [PDF]
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 J. S Kalus and L. R Moser Evolving Role of Low-Molecular-Weight Heparins in ST-Elevation Myocardial Infarction Ann. Pharmacother., March 1, 2005; 39(3): 481 - 491. [Abstract] [Full Text] [PDF]
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J. Hirsh and R. Raschke Heparin and Low-Molecular-Weight Heparin: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 188S - 203S. [Abstract] [Full Text] [PDF]
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 S. Koo, N. Kucher, P. L. Nguyen, J. Fanikos, P. W. Marks, and S. Z. Goldhaber The Effect of Excessive Anticoagulation on Mortality and Morbidity in Hospitalized Patients With Anticoagulant-Related Major Hemorrhage Arch Intern Med, July 26, 2004; 164(14): 1557 - 1560. [Abstract] [Full Text] [PDF]
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K. K. Chung, J. K. Tofferi, and W. T. Browne Suboptimal Monitoring and Dosing of Unfractionated Heparin Ann Intern Med, April 6, 2004; 140(7): 582 - 582. [Full Text] [PDF]
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D. J. Quinlan, A. McQuillan, and J. W. Eikelboom Low-Molecular-Weight Heparin Compared with Intravenous Unfractionated Heparin for Treatment of Pulmonary Embolism: A Meta-Analysis of Randomized, Controlled Trials Ann Intern Med, February 3, 2004; 140(3): 175 - 183. [Abstract] [Full Text] [PDF]
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