Thrombolytic therapy of pulmonary thromboembolism

Abstract

MPLOYMENT of thrombolytic agents for the treatment of pulmonary thromboembolism is an attractive and rational concept based on a number of considerations. The process of pulmonary embolism involves compromise of the cross-sectional area of the pulmonary circulation by embolization of thrombotic material composed primarily of red cells enmeshed in a fibrin lattice. Damage to the pulmonary parenchyma results from the compromised circulation distal to the embolic material, and the hemodynamic alterations are due to the increased pulmonary resistance and its adverse effect on the right ventricle caused by the obliteration of the pulmonary bed. Removal of the embolic material immediately reverses the hemodynamic consequences, and probably also the effect on the pulmonary parenchyma, and in most instances restores the involved branches of the pulmonary artery to the state of normalcy that existed prior to the embolization. Recent emboli are favorable to lyse if exposed to plasmin because the embolic material is from freshly formed thrombi, usually no more than a few days old, and because there is often fragmentation of the thrombus as it embolizes, which exposes the inner aspects of thrombus. Thus, the administration of agents that greatly enhance fibrinolytic activity in plasma should lead to accelerated resolution of the embolic material. While spontaneous embolus resolution is the rule rather than the exception, the time required for this physiologic process is usually measured in days or weeks rather than in hours. More rapid reversal of the adverse consequences of an embolic episode may be desirble, especially in the patient who has marked hemodynamic effects of embolization. In such patients, deterioration of cardiopulmonary function is rapid after embolism, and prompt rapid restoration of normal blood flow may be important and, in fact, life saving. Theoretically, an additional benefit would be reduced likelihood of recurrent pulmonary embolism by inducing lyses of thrombi present in the veins in the lower extremities. These and other considerations have encouraged the evaluation of thrombolytic agents in acute pulmonary embolism. BACKGROUND INFORMATION