Search

Disruption of an atherosclerotic plaque in coronary arteries with a minor stenosis is the usual stimulus for acute coronary thrombosis and myocardial infarction. In this article the pathogenesis of arterial thrombosis and contributions of local arterial wall substrates, the rheology of blood flow, systemic factors, and the critical role of thrombin in the formation of thrombus are discussed. More potent antithrombotic therapy may accelerate exogenous thrombolysis, allows endogenous thrombolysis, and should reduce recurrent infarction and ischemia and death, as well as need for coronary revascularization. Maximal antithrombotic therapy for acute myocardial infarction includes an intravenous bolus of heparin at 100 U/kg followed by an intravenous infusion--at 1,200 U/hr for patients weighing 60-80 kg, 1,300 U/hr for those weighing [greater than] 80 kg, and 1,000 U/hr for those weighing [less than] 60 kg (or 17 U/kg/hr)--to maintain the activated partial thromboplastin time at 2-3 times control (60-90 sec) for at least 5-7 days. To convert intravenous to subcutaneous administration, use 14,000-17,000 U every 12 hours and initially overlap the intravenous infusion by 2 hours. The loading dose of aspirin on admission to the hospital is 160 mg followed by 80 mg/day. High-risk patients should be considered for conversion of heparin to warfarin therapy for at least 3 months at an international normalized ratio of 2.5-4.0 for the prevention of recurrent ischemia, reinfarction, death, thromboembolism, reactivation of thrombosis, and reduced necessity for revascularization.

Therapeutic strategies and clinical trials in unstable angina should be based on the pathogenesis, risk, and mechanisms of thrombosis. The mechanisms of thrombosis and the differences in the effects of anticoagulant, antithrombotic, antifibrin, and antiplatelet drugs must be taken into account when determining the dosage and duration of therapy. Ignoring these principles may prevent identification of new therapy, increase the cost of new drug development and research, increase the cost of new drugs, and increase the cost of medical care., A thrombus is a clump of various kinds of blood cells, including platelets, fibrin, clotting factors, and other components, that attaches itself to the inside wall of an artery. Thrombosis usually occurs after the cells lining the interior wall of an artery have been injured. Disruption of atherosclerotic plaques causes unstable angina (chest pain due to reduced blood flow to the heart muscle), heart attack and sudden cardiac death. The physiological aspects of thrombus formation and plaque rupture are described. Vasoconstriction (constriction of a blood vessel) commonly occurs after injury to a vessel wall. This type of injury may occur during balloon angioplasty, a technique that employs a balloon-tipped catheter to widen arteries narrowed by atherosclerotic plaques. Delayed angiography (imaging of the heart and blood vessels) should be performed following angioplasty to detect and treat vascular injury. Unstable angina often precedes a heart attack or other condition that results from clot-related arterial blockage. Treatment of unstable angina with combined anticoagulation (heparin) and low-dose aspirin is recommended, although this combination has never been tested against single therapy. Recommended medications and their dosages are described. The appropriate use of thrombolytic therapy, and the development of new antithrombotics are also discussed. (Consumer Summary produced by Reliance Medical Information, Inc.)

Survival of patients with acute transmural infarction is largely related to the size of the myocardial infarction. The goal of thrombolytic therapy in acute myocardial infarction is maximal salvage of myocardium by reestablishment of flow in the occluded infarct-related artery and the establishment and maintenance of a patent infarct-related artery. Results of randomized trials show a significant reduction in mortality in patients who have undergone thrombolysis. A patent infarct-related artery, even in the absence of a change in left ventricular function, is associated with reduced mortality. The Thrombolysis in Myocardial infarction Trial and the European Cooperative Trial showed that recombinant tissue-type plasminogen activator is superior to streptokinase in reestablishing flow in a totally occluded artery. Experimental and clinical evidence suggests that thrombolysis and thrombosis occur simultaneously, and that lysis appears to increase both thrombin and platelet activity. Effective reduction of thrombosis accelerates thrombolysis. Rethrombosis after thrombolysis is due to anchored residual thrombus, which alters the hemorrheology of blood flow and produces a highly thrombogenic substrate that is largely due to residual fibrin-bound thrombin. Platelet deposition is directly related to severity of residual stenosis and shear rate. Thrombin appears to be the most potent of the 5 potential stimulators of platelet activation during arterial thrombosis. Proper anticoagulation can play an important role in reducing thrombosis. Experimental evidence strongly supports the use of heparin during and after thrombolysis. A recently reported study shows continued reduction of residual stenosis after 1 month of vigorous anticoagulation with intravenous heparin and subsequent oral anticoagulation. A recent clinical trial showed that subcutaneous heparin given during hospitalization reduced recurrent ischemia after thrombolysis, mortality and left ventricular mural thrombosis. Most current trials are using both heparin and aspirin during and after thrombolysis, with apparent reduction in rates of reocclusion. Thrombolysis with a combination of recombinant tissue-type plasminogen activator and either streptokinase or urokinase appears to reduce reocclusion. Maximal therapy to enhance continued lysis of residual mural thrombus after hospitalization includes combined anticoagulation with sodium warfarin and probably low-dose aspirin at 80 mg/day. (Am J Cardiol 1990;6S:12C-19C), Improvements in the treatment of acute arrhythmias (abnormal heart rhythms) has led to increased survival following acute myocardial infarction (heart attack, which usually occurs when a coronary artery is blocked by a thrombus or blood clot). Long-term survival depends on re-establishing adequate blood flow to the parts of the heart muscle supplied by the occluded artery. In this regard, enormous strides are being made in the application of thrombolytic therapy, the use of enzymes to dissolve clots and re-open an artery blocked by a thromboembolus and re-establish blood flow. As might be expected, the treatment is most effective when administered soon after the onset of myocardial infarction. The use of thrombolytic therapy is not without risks; a reliable diagnosis of myocardial infarction is very important. Generally, patients over 75 should not receive thrombolytic therapy, nor should patients at risk for hemorrhage. Hemorrhage risk factors include uncontrolled hypertension, a previous cerebrovascular event, prolonged cardiopulmonary resuscitation, and recent surgery. Evidence from a number of sources indicates that thrombus formation and lysis are ongoing simultaneously, a fact that has direct clinical significance. The addition of heparin to thrombolytic therapy improves effectiveness, and in experimental studies has improved thrombolysis by 50 percent. The residual thrombus left after thrombolytic therapy provides a potent stimulus for rethrombosis; this stimulus may be more powerful than that of a deeply injured arterial wall. Anticoagulation therapy reduces the size of the residual thrombus and reduces the risk of rethrombosis. Although the proper dosage and effectiveness of heparin during and after thrombolysis has not been determined by randomized clinical trials, empirical evidence suggests that a bolus of 150 units per kilogram of heparin, given with the thrombolytic agents, followed by 1,000 units of heparin per hour is effective. After about 12 hours, the heparin dose may be adjusted to maintain activated partial thromboplastin times at 2 to 3 times normal. (Consumer Summary produced by Reliance Medical Information, Inc.)

An approach to the management of thrombosis and embolism in various cardiovascular disorders is discussed. This approach is based on current knowledge of pathogenesis and risk of thromboembolism. Rational therapeutic guidelines are formulated along the lines of anatomic location (arterial circulation, cardiac chambers or prosthetic valves), pathophysiology (activation of platelets or the coagulation system, or both), and degree of thromboembolic risk. With clear understanding of these factors, it may be possible to determine the most suitable platelet inhibitor or anticoagulant regimen for the individual patient, and whether these agents should be given singly or in combination. (Am J Cardiol 1990;6S:38C-44C), Blood clots that obstruct blood vessels are majors causes of illness and death. The management of thrombosis, the development of a blood clot within a vessel or the heart, and embolism, the obstruction of blood vessel by a clot (which has usually travelled within the circulation from a larger to a smaller vessel) is not straightforward. Careful analysis of the causes of thrombosis and embolism and the associated risks is required before appropriate therapy can be instituted. In the nineteenth century, the famous pathologist Virchow described his 'triad' of causes for thrombosis: injury to the endothelia (the inner lining of blood vessels and the heart), static blood flow, and hypercoagulability of the blood. Although a tremendous amount has been learned about the process of blood clotting, these three principles are still a useful guideline. The greatest risk of thrombosis within an artery occurs in patients with unstable angina, acute myocardial infarction, and immediately after arterial surgery. Moderate risk occurs with stable angina, the chronic phase after myocardial infarction, and after arterial surgery. The greatest risk of thrombosis within the chambers of the heart itself are associated with atrial fibrillation, mitral stenosis, and uncontrolled hyperthyroidism. Patients with atrial fibrillation and other forms of heart disease have a moderate risk, and patients under 60 with no other evidence of disease are at relatively low risk. Patients with implanted heart valves are at high risk of thrombosis, with mechanical valves presenting more risk than bioprostheses; a patient with a bioprosthesis and normal atrial rhythm has a significantly lowered risk. The treatment of these patients should be balanced against risks. High risk patients may be treated with warfarin (coumadin); dipyridamole may be added for very high risk patients, such as those with mechanical heart valves. Warfarin is indicated for patients at medium risk for thrombosis within the heart, but aspirin may be satisfactory for patients with medium risk of arterial thrombosis, such as some patients with myocardial infarction. Patients at low risk may not require antithrombotic therapy, or may be adequately managed with aspirin. (Consumer Summary produced by Reliance Medical Information, Inc.)