Thrombosis and the pharmacology of antithrombotic agents

OBJECTIVE: To provide an overview of the current state of knowledge regarding the physiology of hemostasis, the pathophysiology of thrombosis, and the pharmacology of antithrombotic agents. DATA SOURCES: A MEDLINE search was conducted to identify pertinent literature published since 1984. Recently published textbooks devoted to the subjects of hematology, hemostasis, and thrombosis also were reviewed, particularly their bibliographies. The bibliographies of selected review articles also were reviewed. STUDY SELECTION: As the amount of literature was vast, only the most significant and noteworthy published studies were reviewed. Review articles and book chapters authored by researchers of international reputation also were reviewed. DATA EXTRACTION: Identified studies from the primary literature and selected reviews were analyzed carefully. Information regarding hemostasis, thrombosis, and antithrombotic drugs was extracted. Particular attention was given to data regarding drugs currently available or soon to be available on the US market. DATA SYNTHESIS: Knowledge regarding the regulation of blood coagulation has expanded substantially in recent years. Hemostasis involves the dynamic interplay of numerous intravascular constituents, including the vessel wall, circulating procoagulants and anticoagulants, platelets, and fibrinolytic proteins. Thrombosis is the abnormal formation of a clot within the vascular system. When sufficiently large, thrombi can prevent the flow of blood and nutrients to vital tissues. Thrombosis is associated with many common diseases and is among the leading causes of death in developed countries. Many drugs are now available to prevent the formation and propagation of thrombi. These agents work by different pharmacologic mechanisms and are useful in different clinical situations. CONCLUSIONS: Thrombosis research has increased our understanding of the pharmacology of antithrombotic drugs and promoted the discovery of new agents targeted more specifically toward the critical steps in pathologic clot formation. New agents have the potential for greater efficacy and fewer adverse effects. An increased understanding of hemostasis, thrombosis, and the pharmacology of antithrombotic drugs should enable the clinician to use these agents appropriately.

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