Atherosclerosis: Coagulation and Fibrinolysis

Abstract

Tissue factor (TF) protein was overexpressed by macrophages and smooth muscle cells (SMCs) and deposited in the extracellular matrix of atherosclerotic intimas, probably resulting in enhanced procoagulant activity and the intimate participation in either thrombus formation or intimal fibrin deposition after the exposure of flowing blood and permeated fibrinogen to TF in atherosclerotic lesions. On the other hand, APO(a) was localized both in the stroma and within some macrophages. Fibrin deposition, which was more frequently detected in the matrix of advanced lesions than in that of early lesions, occasionally colocated with cell- and matrix-associated TF and APO(a) deposited in the matrix. These findings further support the hypothesis that the coagulation and fibrinolysis systems can play an essential role in the initiation and progression of atherosclerosis through fibrin deposition both in atherosclerotic plaques and on the arterial surface by neointimal hypercoagulability and a hypofibrinolytic state, which can also participate in SMC proliferation due to the decreased activation of TGF-beta by embedded and deposited APO(a). The clinical implications of these phenomena may thus contribute to future investigations in the prevention and treatment of atherosclerotic diseases.

Higher CHA2DS2-VASc Score Is Associated With Increased Mortality in Acute Pulmonary Embolism

“…21,24,[29][30][31][32] Activation of platelets and coagulation cascade triggered by atherosclerosis that causes fibrin turnover is the basis of pathogenesis consequently. [33][34][35][36] Diabetes mellitus is associated with increased levels of procoagulant factors. 37 Dyslipidemia is associated with hypercoagulability, endothelial dysfunction, and increased platelet aggregation.…”

Standard Heparin versus Low-Molecular-Weight Heparin

“…Reduced platelet activation could imply less platelet impairment and less risk of bleeding episodes since there are fewer functionally exhausted platelets circulating in the blood stream. In addition, during the progression of the atherosclerotic disease, the vascular intima becomes more thrombotic than with nondiseased arteries, not only as a result of the procoagulant and hypofibrinolytic activities going on in the subendothelial matrix and atheromatous gruel, but also due to any endothelial injuries resulting from rupture or ulceration of the atheromatous plaques [39]. Sueishi et al [39]have demonstrated that in the atheromatous plaque tissue factor activity, assessed as factor X activation, is overexpressed.…”

“…A reduction in lipolytic activity related to cyclic heparinization could be a further possible mechanism: cyclical and prolonged SH treatment activating lipoprotein lipase (LPL) causes a progressive decrease in lipolytic activity and accumulation of chilomicrons [25, 38]. Liu et al [39]have shown that LMWH has a lower affinity to LPL. This does not result in any lower ability to release LPL from endothelial binding sites in peripheral tissues, but mainly in a lesser ability of LMWH to prevent hepatic clearance of LPL [38].…”

An Association between Atherosclerosis and Venous Thrombosis

“…[17][18][19][20][21][22][23] A role of this prothrombotic state in promoting venous thrombosis is plausible, on the basis of the assumption that activated platelets and coagulation factors appear in the slowflowing venous system. High d -dimer levels have been found to be associated with an increased risk of venous thromboembolism 37,38 and recurrent venous thromboembolism.…”

“…[13][14][15][16] Furthermore, atherosclerosis is associated with activation of both platelets and blood coagulation as well as an increase in fibrin turnover, which can lead to thrombotic complications. [17][18][19][20][21][22][23] In subjects without symptomatic atherosclerosis, carotid plaques are considered a reliable marker of arterial disease elsewhere in the circulation. [24][25][26][27][28] To determine whether an association exists between asymptomatic atherosclerotic disease and the risk of venous thromboembolism, we assessed whether vessel-wall plaques were present and, if so, quantified them by means of carotid-artery ultrasonography in a consecutive series of patients with acute venous thrombosis and in a control group of subjects without thrombosis.…”