Pathobiology of thrombin in acute coronary syndromes☆,☆☆,★

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Abstract

Am Heart J 1998;136:S19-S31.

Section snippets

Vascular Atherothrombosis: Basic Principles

Under normal physiologic conditions blood components do not interact with an intact vascular endothelium. The exposure of circulating blood to disrupted or dysfunctional surfaces initiates a series of complex yet orderly biochemical events that give rise to the rapid deposition of platelets, erythrocytes, leukocytes, and insoluble fibrin, producing an initial hemostatic plug that initiates and organizes the repair process.

In most instances thrombosis occurring within the arterial system is

Platelet deposition

Platelets attaching to nonendothelialized or disrupted surfaces undergo adherence, activation, and aggregation along the involved area with the formation of a rapidly enlarging platelet mass. Under physiologic conditions this represents a primary step in hemostasis. In pathologic thrombosis platelet adherence initiates a process that, if poorly regulated, can ultimately lead to circulatory compromise.

The process of platelet deposition involves (1) platelet attachment to collagen or exposed

Acute myocardial infarction (MI)

Occurring in upward of 1 million individuals yearly in the United States, MI represents the most commonly observed arterial thrombotic event in clinical practice. In most cases fissuring or rupture of an atherosclerotic plaque within a major epicardial coronary artery is followed by occlusive thrombosis, typically anchored to the damaged vascular surface and exposed plaque components.

Although hard collagenous material (sclerosis) contributes the most voluminous component of a coronary arterial

Molecular and Cellular Biology of Atherosclerotic Plaques in Acute Coronary Syndromes

Pathologic studies performed on patients who have died suddenly or have recently had an episode of unstable angina or MI often reveal intraluminal thrombus anchored to a ruptured atherosclerotic plaque.8 Primarily based on the results of in vitro experiments and studies conducted in static systems, the thrombogenic capacity of atherosclerotic plaques has been attributed to collagen, fatty acids, and phospholipids. Fernandez-Ortiz et al9 recently investigated dynamic thrombus formation with an

Thrombin: Biochemistry and Plasma Markers

This section will review the biochemistry of α-thrombin with particular attention focused on hemostatic markers available to monitor the generation, activity, and regulation of the enzyme and the potential role of these markers in understanding coronary vascular pathologic conditions. The integrity of the mammalian circulatory system is maintained by the integrated arms of the blood coagulation system. Vascular damage triggers the hemostatic mechanism through a series of complex and highly

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    ☆

    From the aCardiovascular Thrombosis Research Center, University of Massachusetts Medical School; the bDepartment of Pathology, University of Vermont Medical School; cNational Blood Service; and dHospital de L’Hotel-Dieu.

    ☆☆

    Reprint requests: Richard C. Becker, MD, Director, Thrombosis Research Center, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 06155.

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