Damage to the vascular endothelium, such as caused by atherosclerotic plaques, can result in clot formation. Blood clots can occlude the vessel at this site of formation (thrombus), or they may break free from the site and travel as an embolus until they occlude the lumen of the smaller vascular segment. Emboli formed on the venous side of the circulation generally are trapped in the pulmonary vasculature, and emboli formed on the arterial side of the circulation generally occlude blood flow to the region of an individual organ.
The cells of the brain and the heart are particularly susceptible to damage caused by the interruption of blood flow from an embolus. Occlusion of a region of the cerebral circulation results in a stroke, and occlusion of a region of the coronary circulation results in a myocardial infarction.
A blood clot consists of a fibrin mesh that traps platelets and red blood cells (see Fig. 27-1). The fibrin mesh results from the activation of the clotting cascade through either an intrinsic stimulus (vascular stasis) or an extrinsic pathway activation (contact with damaged vascular endothelium). Activated platelets contribute both to the clot and to the activation of the intrinsic pathway.
In this patient, a blood clot has resulted in occlusion of the coronary blood vessel and ischemic damage to the myocardium. Although the individual had coronary vascular stenosis, the sudden onset of severe pain in the absence of exercise is a common characteristic of a thrombus. Abnormalities noted during the physical examination are due to a strong sympathetic nervous system activation. This includes an elevated heart rate and elevated blood pressure from the increase in total peripheral resistance, sweating from the sympathetic cholinergic activation of the sweat glands, pale cold skin from sympathetic constriction of the cutaneous vasculature, and the sympathetically mediated increase in respiratory rate.
Laboratory studies are consistent with myocardial ischemia. The ischemic region of the myocardium causes an electrical abnormality called an “ST segment shift.” The particular leads involved allow determination of the region of the heart that is ischemic. Myocardial enzymes that are normally intracellular begin to leak out from the damaged myocardial tissue. There is an early elevation in troponin and, after 24 hours, there is an elevation in the myocardial band isoform of creatine kinase (CK-MB). Because the infarct is relatively recent, the CK-MB levels are not yet elevated.
Acute resuscitation is centered on limiting ischemic damage, followed by reestablishment of blood flow. Chronic treatment is centered on diminishing the potential for future clot formation.
Ischemic damage is limited by the early administration of supplemental oxygen and the use of nitroglycerin as a coronary vasodilator. This ensures that any vascular segments that can be perfused are being supplied with oxygen-enriched blood.
tPA is used to stimulate the activity of the enzyme plasmin, which dissolves existing clots. Consequently, this class of drugs is often referred to as “clot busters.” tPA is effective when administered early in the episode of ischemia, but its usefulness is diminished if the ischemia has persisted for more than 6 hours.
The tendency for future clot formation can be diminished acutely by treatment with heparin or chronically by treatment with dicumarol (see Fig. 25-1). Heparin potentiates the action of antithrombin 3 and diminishes formation of the fibrin mesh. Dicumarol blocks the vitamin K–dependent synthesis of plasma proteins, which includes almost all of the clotting factors. The delayed effectiveness of dicumarol as an anticoagulant is because the clotting factors already synthesized before beginning the dicumarol treatment remain in the circulation.
Platelets contribute to the formation of platelet plugs as well as clots. The tendency for platelets to adhere and to undergo a release reaction is diminished by aspirin. Consequently, aspirin is sometimes referred to as a “blood thinner.”
