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

22 Apr
2011

The presence of fragment-D dimers in the blood at 1.5 and 3 hours after beginning therapy indicated the in vivo occurrence of clot lysis. Higher levels of fragment-D dimers were present 3 hours after the onset of therapy in the blood of patients who received rt-PA than in patients who received heparin alone (40±29 |xg/ml vs 4±3 ^g/ml) (mean ±SD) (p<0.01). At 3 hours after the start of treatment among patients who received heparin alone, the plasma fibrinogen was 388 ± 126 mg/dl as compared to 222 ± 182 among patients who received rt-PA and heparin (p = 0.14). Among patients treated with 80 mg of i t-PA, however, the plasma fibrinogen at 3 hours was 7 4 ± 51 mg/dl.

The mean angiographic scores were evaluated for patients who had angiograms both before and 2 hours after treatment. Among patients who received rt-PA, the angiographic scores of the left lung were 12.2 ± 5,6 before treatment and 12.5 ±7.4 (mean±SD) after treatment. The angiographic scores of the right lung among patients treated with rt-PA were I0.0±4,4 before treatment and 8.2±3.8 after treatment. Oc­casionally the reduction of the thrombus size with rt- PA was appreciable (Fig 1). Among patients who received only heparin, the angiographic scores of the left lung were 12.9±2.2 before treatment and 12.8 ±4.1 after treatment. The angiographic scores tif the right lung among patients treated only with heparin were 15.5 ±6.3 before treatment and 18.0±10.0 after treatment. Changes of the angio­graphic score with treatment were not significantly different in the comparison of patie nts treated with rt-PA to patients treated with heparin alone.

FIGURE 1. Arteriogram in the left pulmonary artery of patient 11 before treatment (left) and 2 hours after the administration of rt-PA 80 mg (right). The arteriogram shows less obstruction after the administration of rt-PA.

A trend suggested improvement over time of mis­matched perfusion defects among patients treated with rt-PA plus heparin. The presentment, 1 day, 2 day and 7 day mismatched scan deficits respectively were 39 ±18 percent, 29±21 percent, 28±22 per­cent, and 19 ± 14 percent (Fig 2). Among the patients who received heparin alone, mismatched perfusion defects were unchanged during the first two days and decreased only slightly by day 7. Values before treat­ment, at one day, two days, and seven days respectively were 41 ±15 percent, 41 ±18 percent, 40 ±16 per­cent, and 34 ± 18 percent. The trend toward improve­ment among patients treated with rt-PA and heparin did not achieve statistical significance in comparison to the small number of patients treated with placebo and heparin. Viagra Super Active

FIGURE 2. Perfusion scans, (posterior view) in patient 12. Perfusion scans are shown prior to the administration of rt-PA 80 mg and 24 hours, 48 hours, and 7 days after therapy. There was improvement of the perfusion scan 24 hours after treatment with rt-PA.

Among patients treated with rt-PA, the total pul­monary resistance after 1.5 hours decreased from 550 ±220 dyne-s-cm -5 to 360 ±180 dyne-s-cm -5. The pulmonary arterial mean pressure showed no signifi­cant change in these patients (28 ± 9 mm Hg vs 25 ± 8 mm Hg). The total pulmonary resistance after 1.5 hours did not change in patients treated with heparin (770 ±710 vs 760 ±700 dyne-s-cm -5). The pulmonary arterial mean pressure remained unchanged (33 ± 13 mm Hg vs 33 ± 13 mm Hg) among those who received heparin alone. The reduction of total pulmonary resistance among patients treated with rt-PA was greater than the reduction among patients treated with heparin alone (p = 0.03). No prominent changes  were noted either in the respiratory rate or the heart rate over the seven days of the investigation.

Complications

Among the nine patients who received rt-PA, one major bleeding episode occurred in an 81-year-old woman who received 64 mg of rt-PA in combination with heparin. Bleeding occurred in the upper gastro­intestinal tract as well as at sites of catheter insertions and needle punctures. Eight units of packed red blood cells were required. Gastroscopy showed oozing from mild superficial mucosal ulcerations. The patients coagulopathy was corrected and a Greenfield filter was inserted. However, the patient continued to suffer cardiovascular instability, developed a myocardial in­farction, and died of an arrhythmia 19 days after treatment with rt-PA. Serious bleeding was not ob­served among the patients who received placebo plus heparin.

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