Fibrinolysis for acute myocardial infarction: current status and new horizons for pharmacological reperfusion, part 2.

Abstract

Ancillary therapy in association with fibrinolysis may be classified into 2 general categories. Additional therapies may be used to facilitate, enhance, and sustain coronary reperfusion, ie, conjunctive therapy, or to minimize the impact of the ischemic insult to the myocardium and/or consequences of reperfusion injury, ie, adjunctive therapy. ### Conjunctive Therapy An important paradox associated with the use of fibrinolytic therapy is its procoagulant potential. The effect of fibrinolytic agents on platelets is complex, poorly understood, and controversial.1 Conflicting evidence exists concerning the capacity of fibrinolytic agents to activate as opposed to diminish platelet activation; this may relate, in part, to differences in protocol design and methodology for assessment of platelet function, the type of fibrinolytic agent used, and the time course over which the studies are conducted.1 2 3 4 5 6 7 8 9 10 11 12 13 14 Regardless of this controversy, exposure of clot-bound thrombin, when unmasked, becomes an extraordinarily potent platelet agonist that mandates conjunctive antithrombin and antiplatelet therapy as an essential component of any fibrinolytic strategy.5 Activated platelets provide an abundant source of factor Xa on their surface and, through extrusion from their alpha-granules, emit plasminogen activator inhibitor - 1, α2 antiplasmin, platelet factor IV, and a variety of vasoconstrictor substances such as thromboxane α2 and serotonin.1 6 7 The latter substances have been demonstrated to be biologically active in humans. They have also been suggested as the mechanism for no reflow after apparently successful primary angioplasty for thrombotic coronary occlusion and, together with the hematologic mediators, antagonize the prospects of successful fibrinolysis.8 Conjunctive antithrombin therapy with unfractionated heparin is also associated with platelet activation. In summary, the vascular accident causing coronary thrombosis and the therapeutic strategy that incorporates fibrinolysis set the stage for a complex interplay of opposing forces …