Antithrombotic actions of statins.
Aspirin depresses thrombin generation, probably through a mechanism independent of the cyclooxygenase inhibition, but rather related to acetylation of the platelet membrane macromolecules. This action of aspirin is blunted in hypercholesterolemia. In men with marked hypercholesterolemia, lowering serum cholesterol by a three-month simvastatin treatment is accompanied by a reduction of thrombin generation both at basal conditions in venous blood and after activation of hemostasis by microvascular injury. Similar results are obtained in patients with coronary heart disease and borderline - high cholesterol levels. We assessed tissue-factor initiated coagulation in blood samples collected every 30-seconds from bleeding time wounds in patients with advanced coronary artery disease and total cholesterol levels of 224 mg/dL. Three-month simvastatin treatment depressed blood clotting, leading to reduced rates of prothrombin activation, FVa generation, fibrinogen cleavage, FXIII activation, and an increased rate of FVa inactivation. Such a concerted influence of statins on the clotting cascade seems to be independent of their lipid-lowering action and may be the result of depressed isoprenoid production.
Szczeklik
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A
Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland. mmszczek@cyf-kr.edu.pl
Undas
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A
Musial
J
J
Gajewski
P
P
Swadzba
J
J
Jankowski
M
M
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019821:Simvastatin / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D010975:Platelet Aggregation Inhibitors; D019821:Simvastatin