Tissue Plasminogen Activator for the Treatment of Acute Pulmonary Embolism: DISCUSSION

23 Apr


Fibrinolysis occurred within 1.5 hours after receiv­ing rt-PA, based upon the prompt elevation of frag­ment D-dimers. The assay that was used was specific for fibrin and did not detect fibrinogen degradation products. The observed reduction of fibrinogen levels in each of three patients receiving 80 mg of rt-PA was consistent, in addition, with a systemic lysis of fibrin­ogen. In spite of the prompt onset of fibrinolysis, there was only a limited change of the pulmonary vascular resistance and no significant improvement of the angiograms at 2 hours. The perfusion scans, however, showed trends toward more rapid improvement by 24 hours than patients treated with placebo.

Reported experience using rt-PA for venous throm- boemboli in patients is limited, and there are no placebo controlled studies. Bounameaux and associates reported the first treatment of a patient with pulmonary embolism using rt-PA. The patient treated with rt-PA plus heparin showed almost com­plete recanalization of the branches of the left pul­monary artery and recanalization of the vessels to the right lower lobe in 24 hours.

The largest experience with rt-PA in pulmonary thromboembolism was reported by Goldhaber and associates. They administered 50 to 90 mg of rt-PA over a period of 2 to 6 hours in an open fashion. Forty- four of 47 patients had angiographic evidence of clot lysis 6 hours after beginning treatment with rt-PA. Improvement over 6 hours was marked in 27, moder­ate in 12, and slight in five. In this study, two of 47 patients had a major hemorrhagic complication that required surgical control of the bleeding. Hematuria occurred in three patients, periodontal oozing in three patients, and groin hematomas severe enough to preclude the intended full dose occurred in seven patients. Therapy in our investigation differs from the therapy investigated by Goldhaber and associatesprimarily because we administered heparin simulta­neously. Heparin reportedly enhances the fibrinolytic effects of rt-PA and may have contributed to the improvement and the bleeding complication observed in the PIOPED study.
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Goldhaber and associates also compared the effects of rt-PA with urokinase. Twenty-two patients with acute pulmonary embolism were administered rt-PA 100 mg intravenously over 2 hours. Twenty-three patients were given urokinase for varying durations. After 2 hours, 82 percent of the patients treated with rt-PA showed clot lysis compared with 48 percent of the patients treated with urokinase. Among the pa­tients treated with rt-PA, there was 23 percent im­provement in the angiographic score; whereas the patients treated with urokinase showed an 8 percent improvement of the angiographic score. By 24 hours, improvement of the lung scan was identical in the two treatment groups. A decrement of the hematocrit more than ten points was observed in 20 percent of patients treated with rt-PA and 48 percent of patients treated with urokinase. In contrast to this report, we saw no significant clot lysis at 2 hours, but the doses of rt-PA that we employed were smaller.

Verstraete and associates treated 34 patients with acute pulmonary embolism 5 day) with rt-PA in combination with heparin. This aspect of the study was comparable to ours. Two hours after treatment with rt-PA 50 mg, either directly within the pulmonary artery (19 patients) or intravenously (15 patients), reductions of the angiographic severity were 12 per­cent and 15 percent, respectively. After 2 hours, a second administration of rt-PA 50 mg was given to patients with large residual emboli, either intrave­nously (eight patients) or within the pulmonary artery (14 patients). Seven to 18 hours after the beginning therapy, among 22 patients, the angiographic score of severity diminished 38 percent from control. The route of administration did not affect the outcome. An infusion of 100 mg over 7 hours seemed superior to an infusion of 50 mg over 2 hours. Blood transfusions of two or more units were necessary in four patients (12 percent). Less bleeding was observed in 16 other patients (47 percent). kamagra soft tablets

In conclusion, although a thrombolytic effect was induced on the basis of fragment D-dimers by 1.5 hours after the onset of therapy, rt-PA in a dose of 40 or 80 mg produced only modest hemodynamic effects and produced no significant changes of the pulmonary angiogram within 2 hours. The occurrence of one severe hemorrhagic episode among nine treated pa­tients indicates that rt-PA is not without risk.