THROMBOLYTIC THERAPY

Abstract

Physiologic hemostasis provides a delicate balance between thrombosis and fibrinolysis. However, pathophysiologic states develop that promote thrombosis. In recent years, many acute thrombotic syndromes are being treated with thrombolytic agents. As with any medical therapy or intervention, the decision to proceed must be based upon a careful consideration of the indications and contraindications as well as the risks versus the benefits. There are many different conditions that may be treated with thrombolytic agents. Thrombolytic agents have secured a place in the treatment of acute myocardial infarction (AMI) because of their well-validated reduction in mortality. Acute pulmonary embolism is being aggressively treated with thrombolytics. The role of thrombolytic agents in vertebrobasilar thrombosis is currently being explored. In addition, thrombolytics are also being used for the treatment of thromboembolic disease during pregnancy. There are several scenarios in which patients presenting to the operating rooms for anesthesia and surgery may have recently been exposed to thrombolytic agents, presenting perioperative challenges for the anesthesiologist. Thrombolytics have, as a common mechanism of action, the ability to activate one of the proteolytic enzymes, plasminogen. Plasminogen, along with its activators and inhibitors, compose the fibrinolytic system that is ultimately responsible for clot lysis. Physiologic plasminogen activators catalyze the conversion of both unbound and fibrin-bound plasminogen to plasmin. Plasminogen activator inhibitors play a key role in regulating this process. The fibrin-bound plasmin then degrades the fibrin within the thrombus, leading to clot lysis (fibrinolysis). Circulating unbound plasmin degrades fibrinogen (fibrinogenolysis) as well as factors V and VIII, creating a systemic fibrinolysis. The action of circulating alpha2-antiplasmin, which inactivates unbound plasmin, prevents this physiologic process from becoming pathologic. Fibrin-bound plasmin resists inactivation by alpha2-antiplasmin. This allows for the lysis of pathogenic thrombi, while preventing a systemic fibrinolytic state.15