Statins and Blood Coagulation

Abstract

Abstract-The 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors (statins) have been shown to exhibit several vascular protective effects, including antithrombotic properties, that are not related to changes in lipid profile. There is growing evidence that treatment with statins can lead to a significant downregulation of the blood coagulation cascade, most probably as a result of decreased tissue factor expression, which leads to reduced thrombin generation. Accordingly, statin use has been associated with impairment of several coagulant reactions catalyzed by this enzyme. Moreover, evidence indicates that statins, via increased thrombomodulin expression on endothelial cells, may enhance the activity of the protein C anticoagulant pathway. Most of the antithrombotic effects of statins are attributed to the inhibition of isoprenylation of signaling proteins. These novel properties of statins, suggesting that these drugs might act as mild anticoagulants, may explain, at least in part, the therapeutic benefits observed in a wide spectrum of patients with varying cholesterol levels, including subjects with acute coronary events. Key Words: statins Ⅲ blood coagulation Ⅲ thrombin Ⅲ protein C T he 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase inhibitors, the so-called statins, have been proven to be highly effective in the management of hyperlipidemia and the prevention of atherosclerotic vascular disease, especially coronary artery disease (CAD). 1,2 The therapeutic benefits from statin therapy, however, are only poorly correlated with cholesterol lowering, suggesting other mechanisms are at play. Mevalonate, the product of HMGCoA reductase, is the precursor of not only cholesterol but also isoprenoid compounds that permit the attachment of signaling proteins to the cell membrane. 3,4 Abundant experimental and clinical evidence in this rapidly expanding field has resulted in the widely accepted concept of cholesterol-independent pleiotropic effects produced by statins that include alteration of endothelial dysfunction, leading to increased nitric oxide (NO) bioavailability, atherosclerotic plaque stabilization, regulation of angiogenesis, reduction of the inflammatory response, and antithrombotic properties. [5][6][7] Apart from profibrinolytic and antiplatelet effects, reported in several studies, 5,7-9 increasing evidence indicates that the HMG-CoA reductase inhibitors also modulate the blood coagulation cascade at multiple levels, leading to reduced thrombogenicity.The activation of the extrinsic coagulation pathway initiated by an exposure or expression of tissue factor (TF) plays a key role in hemostasis (Figure). The localized process involves multiple components, including blood coagulation factors, platelets, blood cells, the endothelium, and sublayers of a damaged vessel. Platelets provide the catalytic surface for the formation of the procoagulant complexes; the intrinsic factor Xase (FIXa-FVIIIa) and prothrombinase (prothrombin, FXa-FVa). These complexes accelerate thrombin ge...

Beyond Hyperglycemia in Diabetes: Role of Statin Treatment on Thrombogenesis Triggered by Inflammation

“…Statins can interfere at different levels of the inflammatory process, decreasing cholesterol levels, platelet activation and their release of mediators of inflammation. Taken together, these mechanisms may lead to stabilization of the atherosclerotic plaque as well as modulation of the prothrombotic status experimental studies have well established the pleiotropic effects of statins by showing their ability to reduce the inflammatory burden, to modulate endothelial function and the risk of thrombosis, thus reducing the incidence of acute vascular events [18]. Statins have been shown to lead to a significant downregulation of the blood coagulation cascade, independently of changes in lipid profile [18].…”

Effects of rosuvastatin as an adjuvant treatment for deep vein thrombosis

“…Statins have cholesterol-independent pleiotropic eff ects that exert vascular protection by improving endothelial function, regulating angiogenesis, stabilizing atherosclerotic plaques, increasing nitric oxide bioavailability, and reducing thrombogenic and infl ammatory responses [2]. Statins also have an anticoagulant eff ect by decreasing tissue factor expression, which reduces thrombin generation and hence attenuates fi brinogen cleavage and factor V/XIII activation [2].…”

“…In addition, post-thrombotic syndrome (PTS), which is a long-term sequela of DVT, aff ects 23 -60 % of patients and results in a high level of morbidity [1]. Several factors contribute to the development of VTE: alterations in blood fl ow, hypercoagulability of blood, and disruption of endothelial function [2].…”

“…Several vascular pleiotropic eff ects have been described for statins, in addition to modifying the lipid profi le: increased nitric oxide bioavailability, atherosclerotic plaque stabilization, regulation of angiogenesis, reduction of the infl ammatory response, and antithrombotic properties [2]. The anticoagulant properties include reduced tissue factor expression, increased thrombomodulin expression, and favorable alterations to fi brin clot structure.…”

Genotipos frecuentemente asociados a trombofilias

“…Las arterias y las venas son los sitios más frecuentes de aparición de trombosis, también pueden generarse en los capilares o en el corazón, aunque con menor frecuencia. Las complicaciones de la trombosis se originan por el efecto local de la obstrucción del flujo y el posterior desprendimiento y formación del émbolo del material trombótico, o por el consumo de elementos hemostáticos (7).…”