The relevance of this phenomenon could be even more striking when rt-PA is administered in the presence of the large fibrin-rich thrombi encountered in DVT and pulmonary embolism, which are likely to release large amounts of cross-linked FDPs. This may explain the high incidence of bleeding when t-PA is used in treatment of DVT. Limiting…
The extent of fibrinogenolysis was quantified by measuring the levels of B01-42, a fibrinogen-derived fragment released by plasmin early in the course of fibrinogen conversion to fragment X. The presence of a clot increased rt-PA-mediated Bp 1-42 release more than 20-fold. Potentiation of fibrinogenolysis is not the result of enhanced plasminogen activation on the clot…
Even more than the improved efficacy, the major potential advantage of a bolus administration of rt-PA seems to be the reduced risk of hemorrhagic complications. A decrease in the frequency or severity of bleeding, particularly intracranial bleeding, could indeed favor a greater utilization of thrombolytic treatment, particularly in clinical disorders with low mortality, such as…
The differences were particularly striking in samples taken 7 h or more after the administration of the thrombolytic agent. At hour 7, the level of cross-linked FDPs was 5,821 ±1,683 mg/ml in rt-PA-treated patients, compared with 2,924 ±1,186 mg/ml in strep-toldnase-treated patients (p<0.01). A marked and prolonged increase in FDPs in the late-drawn samples was…
Shiftman et al investigated the effects of 2 dosing regimens of rt-PA on pulmonary thrombolysis in a canine model of pulmonary embolism that caused pulmonary hypertension. In that study, rt-PA, 1 mg/ kg, was infused over 15 or 90 min. The shorter infusion resulted in a marked increase in the rate of lysis (56%/h vs…
Rationale for Bolus rt-PA Administration Theoretically, one way to improve thrombolysis is to reach a higher concentration of the lytic agent in the vicinity of the thrombus. The efficacy of intra-arterially administered thrombolytic agents in coronary or peripheral artery obstruction is presumably due to the high concentration of plasminogen activators on the surface and inside…
In most clinical studies, rt-PA was administered by continuous infusion over a period of 90 min to 8 h. The rationale for such a prolonged rt-PA infusion was based on the fear of a high incidence of rethrombosis due to (1) the moderate hemostatic impairment induced by rt-PA; (2) the short half-life of t-PA; and…
In recent years, thrombolytic therapy has become widely used in patients with acute myocardial infarction. Indeed, thrombolytic agents have been shown to induce reperfusion of the occluded coronary arteries, save ischemic myocardium, improve left ventricular dysfunction, and enhance both early and late survival. In contrast, the use of thrombolytic agents remains controversial and infrequent in…
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