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Acute myocardial infarction and the role of aspirin, heparin, and Warfarin

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Summary

Acute myocardial infarction is initiated by plaque disruption of a fatty plaque with a thin fibrous cap which has been infiltrated by macrophages. The macrophages are attracted and stimulated by oxidized lipids to secrete metalloproteinases which dissolve collagen and arterial wall matrix and to synthesize tissue factor which accumulates in the fatty gruel, and initiates the thrombotic process when exposed to flowing blood after plaque disruption. This initiates thrombin generation which is greatly amplified by the coagulation cascade.

Minute amounts of thrombin initiate platelet aggregation, deposition and secretion with growth of platelet-rich thrombus and an accompanying network of fibrin which is at the base of platelet deposition, and increased over regions of deep injury where there appears to be enhanced thrombin generation. Thrombin is necessary for upregulation of platelet membrane receptors, growth of thrombus, maintenance of platelet cohesion, conversion of fibrinogen to fibrin, crosslinking of fibrin and, in part, for activation of the fibrinolytic system.

Thrombosis is directly related to local rheology (shear force, turbulence), thrombogenicity of the exposed arterial wall substrates, and modified by systemic factors. Acute vasoconstriction is directly related to platelet deposition, enhanced by endothelial dysfunction or absence, and increased by hypercholesterolemia which induces production of the potent vasoconstrictor endothelin.

Direct thrombin inhibition with a high affinity inhibitor, such as hirudin, totally blocks growth of thrombus, inhibits fibrin formation at lower doses and platelet deposition at somewhat higher doses, and enhances dissolution of residual thrombus. Dissolution of residual thrombus reduces luminal obstruction, and may reduce the need for revascularization procedures since plaque disruption most often occurs in arteries with minor obstruction (<50% stenosis).

Current recommendations include intravenous heparin 5000 U bolus+1,000 U/hr to maintain the aPTT at 60–85 sec, and aspirin (160–325 mg loading followed by 80 mg/day). Maximal inhibition of thrombus at the culprit lesion includes maintenance of heparin infusion plus daily aspirin and conversion of heparin to warfarin to maintain the INR at 2.0–3.0 for 3–6 months along with aspirin 80 mg/day as suggested by the ATACS trial. The value of fixed-dose warfarin plus lowdose aspirin in the acute and chronic phase after myocardial infarction is currently being evaluated in the Coumadin Aspirin Reinfarction Study.

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Authors and Affiliations

  1. Division of Cardiology, Mt. Sinai Medical Center, 1 Gustave Levy Place, 10021, New York, NY

    J. H. Chesebro

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  1. J. H. Chesebro
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  2. J. J. Badimon
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  3. N. L. Hassinger
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  4. R. D. McBane
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  5. V. Faster
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Chesebro, J.H., Badimon, J.J., Hassinger, N.L. et al. Acute myocardial infarction and the role of aspirin, heparin, and Warfarin. J Thromb Thrombol 1, 231–235 (1995). https://doi.org/10.1007/BF01060732

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