Thrombosis, Embolism, Infarction

Thrombosis, Embolism and Infarction

THROMBOSIS

Thrombus formation (called Virchow's triad): (1) endothelial injury, (2) stasis or turbulent blood flow (3) hypercoagulability of the blood

Endothelial Injury

Endothelial injury is particularly important for thrombus formation in the heart or the arterial circulation, where the normally high flow rates might otherwise impede clotting by preventing platelet adhesion and washing out activated coagulation factors.

Thus, thrombus formation within cardiac chambers (e.g., after endocardial injury due to myocardial infarction), over ulcerated plaques in atherosclerotic arteries, or at sites of traumatic or inflammatory vascular injury (vasculitis) is largely a consequence of endothelial cell injury.

From: Prospects for Cardiovascular Research JAMA. 2001;285(5):581-587. doi:10.1001/jama.285.5.581

Figure Legend:

Chronic endothelial injury, inflammation, and oxidative stress arecentral to the development of atherosclerosis. Endothelial injury

resultsfrom a variety of factors including tobacco use, hypercholesterolemia, interventionaltherapies with angioplasty or coronary

stents, and from ulceration or fissuringof atherosclerotic plaques. At sites of endothelial injury, production ofendothelial-derived

substances (nitric oxide [NO], tissue plasminogen activator[tPA], and prostacyclin [PGI2]) is decreased, creating a

prothromboticenvironment characterized lDipaoteprooftdeoinwsn,lomaydo: in3t/i1m1a/2l0h1y3perplasia, and

by incrCeaopsyerdigphlta?te2le0t1a2nAdmleeurickaoncyMteedaicdahlesion, vasoconAstsrsicotcioianti.oUnl.cAerllartiigohntsorrefsisesrvuerdin.g of the

increasedpermeability atherosclerotic plaque

to plasma results from

degradationof collagen matrix in the fibrous cap by metalloproteases released from macrophages.Exposure of the subendothelium

after plaque ulceration or fissuring leadsto platelet adhesion and aggregation and local accumulation of largely platelet-

derivedmediators (thromboxane A2, serotonin, adenosine diphosphate [ADP],thrombin, platelet activating factor [PAF], oxygen-

derived free radicals,tissue factor, and endothelin) that promote thrombus growth, fibroproliferation,and vasoconstriction. LDL

indicates low-density lipoprotein.

Endothelial Injury

Physical loss of endothelium can lead to exposure of the subendothelial ECM, adhesion of platelets, release of tissue factor, and local depletion of PGI2 and plasminogen activators.

However, it should be emphasized that endothelium need not be denuded or physically disrupted to contribute to the development of thrombosis; any perturbation in the dynamic balance of the prothombotic and antithrombotic activities of endothelium can influence local clotting events.

Thus, dysfunctional endothelial cells can produce more procoagulant factors (e.g., platelet adhesion molecules, tissue factor, PAIs) or may synthesize less anticoagulant effectors (e.g., thrombomodulin, PGI2, t-PA).

Endothelial dysfunction can be induced by a wide variety of insults, including hypertension, turbulent blood flow, bacterial endotoxins, radiation injury, metabolic abnormalities such as hypercholesterolemia.

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