Fibrinolytic Agents

The generation of plasmin from plasminogen by plasminogen activators (fibrinolytic agents) induces a variety of effects in addition to dissolving fibrin strands, degrading fibrinogen, and inhibiting tissue factor pathway and factor VIII. It also, in high concentrations, causes platelet activation. Thus, fibrinolytic agents have both prothrombotic and antihemostatic properties—the latter of which is often augmented by the concomitant use of anticoagulants and platelet antagonists (see Chapter 12). Bleeding is the most common complication of fibrinolytic (and adjunctive antithrombotic) therapy. The most important predictors of nonintracranial hemorrhage are older age, invasive procedures, low body weight, and female sex (de Jaegre et al, 1992; GISSI 2 Investigators, 1990; GUSTO-III Investigators, 1997; INJECT Investigators, 1995). Predictors of intracranial hemorrhage include age (>65 years), low body weight (<70 kg), hypertension on admission, and alteplase (vs. streptokinase) (GUSTO-III Investigators, 1997). The approach to patient management in cases of fibrinolytic-induced bleeding is summarized in Figure 30.1. It is important to consider antithrombotic agents that may concomitantly increase hemorrhagic potential. Factor VIIa (recombinant; NovoSeven) represents a treatment alternative for life-threatening hemorrhagic complications.