Robert J. Glynn, PhD, ScD; Paul M Ridker, MD; Samuel Z. Goldhaber, MD; Julie E. Buring, ScD
Acknowledgments: The authors are indebted to the 39 876 participants in the Women's Health Study for their dedicated and conscientious collaboration and to the entire staff of the study. They also thank Roche Molecular Systems for providing the genotyping platform used in the study.
Grant Support: By the National Institutes of Health (grants HL71221, HL43851, and CA47988). Natural Source Vitamin E Association provided the vitamin E and vitamin E placebo, and Bayer HealthCare provided the aspirin and placebo aspirin.
Potential Financial Conflicts of Interest: Grants received: R.J. Glynn (Bristol-Myers Squibb). Honoraria: J.E. Buring (Bayer HealthCare). Other: J.E. Buring (Bayer HealthCare, Natural Source Vitamin E Association).
Requests for Single Reprints: Robert J. Glynn, PhD, ScD, Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue, Boston, MA 02215; e-mail, email@example.com.
Current Author Addresses: Drs. Glynn, Ridker, and Buring: Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue, Boston, MA 02215.
Dr. Goldhaber: Division of Cardiology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.
Author Contributions: Conception and design: R.J. Glynn, P.M. Ridker, J.E. Buring.
Analysis and interpretation of the data: R.J. Glynn, P.M. Ridker, S.Z. Goldhaber, J.E. Buring.
Drafting of the article: R.J. Glynn.
Critical revision of the article for important intellectual content: R.J. Glynn, P.M. Ridker, S.Z. Goldhaber, J.E. Buring.
Final approval of the article: R.J. Glynn, P.M. Ridker, S.Z. Goldhaber, J.E. Buring.
Provision of study materials or patients: J.E. Buring.
Statistical expertise: R.J. Glynn.
Obtaining of funding: R.J. Glynn, J.E. Buring.
Collection and assembly of data: R.J. Glynn, P.M. Ridker, J.E. Buring.
Glynn R., Ridker P., Goldhaber S., Buring J.; Effect of Low-Dose Aspirin on the Occurrence of Venous Thromboembolism: A Randomized Trial. Ann Intern Med. 2007;147:525-533. doi: 10.7326/0003-4819-147-8-200710160-00004
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Published: Ann Intern Med. 2007;147(8):525-533.
Clinically significant venous thromboembolism (VTE) is an age-related condition that affects 1 to 2 of every 1000 adults per year (1–3). Surgery, trauma, immobilization, and cancer frequently trigger VTE, but between one third and one half of all first VTE events occur without these triggers (3–6).
Short-term aspirin therapy has some efficacy in preventing VTE in certain high-risk patients. A meta-analysis of 62 randomized trials in orthopedic surgical, general surgical, and high-risk medical patients found that a few weeks of antiplatelet therapy (usually with aspirin) reduced the risk for pulmonary embolism by about 67% and the risk for deep venous thrombosis by about 40% (7). Subsequently, the randomized Pulmonary Embolism Prevention trial (8) found a statistically significant 34% reduction overall in risk for VTE associated with short-term aspirin therapy in patients with hip fracture or elective arthroplasty. An updated meta-analysis, focused on patients at high risk for occlusive vascular events, found a statistically significant 25% reduction in the odds of pulmonary embolism associated with antiplatelet therapy (9). However, recent randomized trials indicate that therapy with low-molecular-weight heparin may be more effective than aspirin, and such treatments are preferred in current treatment guidelines (10, 11).
Christian Medical College and Hospital Ludhiana,India
November 1, 2007
Treating the Right Clot: Red vs White Thrombi
Aspirin and other antiplatelet drugs are highly effective at reducing major vascular events in patients who are at risk for or who have established atherosclerotic disease.1 Evidence suggests that antiplatelet agents can lower the risk for venous thromboembolism (VTE) in high-risk patients.2 Why aspirin is not effective for primary prevention of VTE in women at low to moderate risk as seen in the present study? Part of the answer to this question may be found in the differences in thrombus formation between the arterial and venous systems. The low-flow and low- pressure venous system is susceptible to reduced blood flow (stasis) and systemic activation of the coagulation cascade, as Virchow described more than 150 years ago, which predisposes to a thrombus even in a nonstenotic vessel. Most venous thrombi consist predominantly of red cells enmeshed in fibrin and contain relatively few platelets; hence, they have been described pathologically as "red thrombi." In contrast, in the high-flow and high-pressure arterial system, thrombi form under the influence of local shear forces, platelet activation, and exposure to thrombogenic substances on damaged vascular surfaces. Arterial thrombi, referred to as "white thrombi," typically are composed predominantly of platelets with relatively little fibrin or red-cell accumulation. Thus, it is plausible to expect that an anticoagulant would be used to prevent venous thromboemboli, whereas an antiplatelet agent would be used to prevent arterial thrombosis.3
1. Antiplatelet Trialists' Collaboration. Collaborative overview of randomised trials of antiplatelet therapy: III. Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. BMJ 1994; 308:235"“246
2. Pulmonary Embolism Prevention (PEP) Trial Collaborative Group. Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) Trial. Lancet 2000; 355:1295"“1302
3. Richard N. Mitchell : Hemodynamic Disorders, Thromboembolic Disease, and Shock in Robbins and Cotran Pathologic Basis Of Disease 7th Ed. Saunders. 2004 pp119-144
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