Effects of intravenous urokinase versus alteplase on total pulmonary resistance in acute massive pulmonary embolism: a European multicenter double-blind trial. The European Cooperative Study Group for Pulmonary Embolism.

Twelve centers participated in a double-blind study in which 63 patients with angiographically documented acute massive pulmonary embolism were randomly assigned to treatment with either urokinase (4,400 U/kg as an intravenous bolus infusion, then 4,400 U/kg per h over 12 h; n = 29) or alteplase (10 mg as an intravenous bolus infusion, then 90 mg over 2 h) followed by heparin (n = 34). The primary objective was to compare the resolution of pulmonary embolism as judged by the change in total pulmonary resistance over the initial 2 h. Further objectives were to evaluate the changes in total pulmonary resistance over the next 10 h and the degree of angiographic resolution at 12 to 18 h. At 2 h, total pulmonary resistance decreased by 18 +/- 22% in the urokinase group and by 36 +/- 17% in the alteplase group (p = 0.0009). Continuous monitoring of pulmonary artery mean pressure, cardiac index and total pulmonary resistance revealed that these variables improved faster in the alteplase group, with consistently significant intergroup differences from 30 min up to 3 to 4 h. After 12 h, the decrease in total pulmonary resistance was 53 +/- 19% in the urokinase group compared with 48 +/- 17% in the alteplase group and the reduction in the angiographic severity score was 30 +/- 25% compared with 24 +/- 18%, respectively, with no significant intergroup differences. Bleeding was equally frequent in the two treatment groups, except that more urokinase-treated patients experienced hematomas at puncture sites.     

Thrombolytic therapy in pulmonary embolism. Which patient should be treated, which regimen should be used?

Summary The indications of thrombolytic therapy in the management of pulmonary embolism remain unclear. Thrombolysis is a lifesaving procedure in patients with major embolism and cardiogenic shock, but in patients with normal blood pressure, randomized studies did not show a decrease in mortality in patients receiving thrombolysis. Recent data however suggest that this therapy may be beneficial in patients with major pulmonary embolism and evidence of right ventricular afterload. Several controlled studies have compared different thrombolytic regimen in patients with pulmonary embolism and indicate that a 2-h infusion of rtPA or urokinase is more rapidly effective than a 12 to 24-h infusion of either streptokinase or urokinase and that a 0.6 mg/kg bolus injection of rtPA is as effective and safe as the 2-h 100 mg regimen.     

58例急性肺栓塞治疗方案的选择与评估

目的 探讨急性肺栓塞（ＡＰＥ）的最佳治疗方案。评估重组组织型纤溶酶原激活剂和尿激酶（ＵＫ）２小时连续静脉溶栓法的可行性及临床疗效。方法 ５８例经放射性核素肺灌注通过扫描（ＥＣＴ）或选择性肺动脉造影（ＣＰＡ）确诊为ＡＰＥ的患者,采用ｒｔ－ＰＡ或ＵＫ２小时连续静脉滴注法（简称２小时法）或ＵＫ小剂量每日１次３￣７日法溶栓及单纯抗凝法,栓子切除法治疗。比较并分析不同治疗方案的临床疗效。结果 溶栓治疗４１例     

Effectiveness and safety of bolus administration of alteplase in massive pulmonary embolism.

Animal studies have demonstrated that thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) is accelerated and that bleeding is reduced when rt-PA is infused over a short period. Previous clinical studies in patients with venous thromboembolism have shown that rt-PA is an effective thrombolytic agent when administered by continuous infusion over 2 to 24 hours. Clinical experience of bolus rt-PA administration in patients with massive acute pulmonary embolism (PE) is, however, limited. A prospective open study was conducted in which 54 patients with massive PE (Miller index > or = 20 of 34) received a 10-minute infusion of rt-PA at a dose of 1 mg/kg. Perfusion lung scanning was used to assess the change in pulmonary perfusion after drug administration. At 48 hours and 10 days, the mean absolute improvements in the perfusion defect were 11 and 31%, respectively. In addition, a significant clinical improvement occurred within 2 hours in 11 of the 15 shocked patients. Five patients died (9%) as a result of persistent shock (3 patients), neurologic damage (1 patient) or intracranial bleeding (1 patient). Major bleeding occurred in 8 patients (15%). Long-term follow-up information was available for 44 of the 49 discharged patients: 2 had died and 12 (27%) complained of persistent exertional dyspnea, 7 of whom had an associated heart or lung disease or chronic thromboembolism at admission. These results suggest that a bolus regimen of rt-PA could provide a convenient approach to thrombolytic therapy in patients with massive PE.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravenous recombinant tissue plasminogen activator (rt-PA) and urokinase in acute myocardial infarction: results of the German Activator Urokinase Study (GAUS)

The effects of recombinant tissue plasminogen activator (rt-PA) and urokinase on patency and early reocclusion of infarct-related coronary arteries were investigated in a single blind, randomized multicenter trial in 246 patients with acute myocardial infarction of less than 6 h duration. Both 70 mg of single chain rt-PA with an initial bolus of 10 mg and 3 million units of urokinase with an initial bolus of 1.5 million units were given intravenously over 90 min. The first angiographic study at the end of the infusion revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction trial [TIMI] grade 2 or 3) in 69.4% of 121 patients given rt-PA versus 65.8% of 117 patients given urokinase (p = NS). Among patients treated within 3 h from symptom onset a patent infarct-related artery was found in 63.9% of 72 patients given rt-PA versus 70% of 70 patients given urokinase (p = NS). There were five cardiac deaths in each group and one fatal intracranial hemorrhage in the rt-PA group. The in-hospital reinfarction rate was 8.9% versus 13.2% for patients treated with rt-PA and urokinase, respectively. There was no difference in left ventricular function at baseline and follow-up catheterization studies. Both drugs were well tolerated and there was no significant difference in cardiovascular or bleeding complications between the two groups. It is concluded that rt-PA and urokinase in the dosages used provide similar efficacy and safety in the treatment of acute myocardial infarction. Reocclusion during the first 24 h may be less frequent after urokinase treatment.     

29例急性肺栓塞临床观察及治疗研究

目的分析急性肺栓塞的临床特点,观察溶栓抗凝治疗对急性肺栓塞的临床治疗效果。方法２９例肺栓塞患者根据放射性核素肺灌注通气检查、选择性肺动脉造影或超声心动图确诊。对其中２３例肺栓塞患者行静脉溶栓加抗凝治疗２９例次;６例肝素抗凝治疗,以临床及核素检查评价其治疗效果。结果男性患者中以年轻超力型发病者较高,女性患者以更年期以后发病明显增高。院外误诊率高达７５．９％。临床上以呼吸困难为主要表现者多见;尿激酶或重组组织型纤溶酶原激活剂（ｒｔ－ＰＡ）溶栓２９例次,总有效率为６５．５％。根据本组有限病例观察溶栓效果与栓塞的面积未见差异,而与发病开始到溶栓治疗的时间密切相关（Ｐ＜０．０５）。肝素抗凝６例,１例显效,２例有效,３例无效。结论应提高对急性肺栓塞的警惕性,减少误诊率;尿激酶或ｒｔ－ＰＡ对急性肺栓塞溶栓抗凝治疗安全有效,溶栓时间越早越好;对有溶栓适应证的患者应首选溶栓治疗。     

Thrombolytic treatment of acute pulmonary embolism

Many investigators have reported about beneficial results with thrombolytic therapy in patients with acute pulmonary embolism. Streptokinase and urokinase have been used for more than 15 years, but the conditions of use of these agents still remain controversial. Optimal dosage and treatment schedule are still evolving. For streptokinase most investigators adopt a fixed dosage schedule: a loading dose of 250,000 units followed by a maintenance infusion of 100,000 units per hour for 24 to 72 hours. For urokinase numerous dosage regimens have been used such as: high dosage schedule 4,400 units per kilogram per hour for twelve to 24 hours with or without loading dose; moderate dosage 1,600 to 2,000 units per kilogram per hour for 24 hours and low dosage in bolus. With these treatments there is a trend to reduced in-hospital-mortality in massive pulmonary embolism; the early pulmonary revascularization and the hemodynamic improvement are higher than those noticed with heparin. These results are obtained with a minimum of complication essentially bleeding in 10 or 15%; most bleeding being located at puncture site. More recently, new thrombolytic agents have been used in acute pulmonary embolism. Only four studies have tested rt-PA which is effective and relatively safe, but the optimal dose regimens remain to be determined. Less information is available concerning Anisoylated Plasminogen Streptokinase Activator Complex (APSAC), the angiographic improvement seems to be rapid and important (50% on average) but the decrease of fibrinogen is important too and comparable with streptokinase. Considering the good results of thrombolytic treatment of acute submassive and massive pulmonary embolism, there is a doubt as to whether the pulmonary embolectomy has any place in the pulmonary embolism patients except in those with cardiac arrest. In the near future new thrombolytic drugs could be more efficient on pulmonary embolism and deep venous thrombosis, and thus the bleeding risk might be decreased.     

Management of mobile right heart thrombi: a prospective series

BACKGROUND: Mobile right heart thrombi (MRHT) are uncommon but their true prevalence is unknown. The aim of our study was to assess the prevalence of MRHT by a systemic use of transthoracic echocardiography in a prospective series of consecutive patients admitted for acute severe pulmonary embolism (PE) and to adopt intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) as the first line intention to treat patients with proven MRHT. METHODS AND RESULTS: We performed a systematic transthoracic echocardiogram from November 1997 to June 1999 in 335 consecutive patients admitted for suspected acute massive PE in whom the diagnosis was subsequently confirmed by perfusion lung scan or angiography. MRHT was identified in 12 of the 335 patients (4%). Nine patients presented a coil form and three patients a ball form. The thrombolytic employed in all cases was rt-PA according to the following protocol: 10 mg in a bolus and 40 mg over 2 h, followed by 50 mg over 5 h, up in a total dose of 100 mg, associated with a bolus of 5000 units of heparin. Control echocardiograms were performed 12 h after the initiation of treatment and at 12-month follow-up. Three patients died before the onset of thrombolytic infusion. The nine remaining patients were submitted to thrombolytic therapy using rt-PA. In seven of the nine remaining patients, MRHT was no longer observed after 12 h and the echocardiographic signs of RV overload had disappeared. The two last patients required adjunctive surgery because of evidence of persistent thrombus in a pulmonary artery. After 24 h, both scintigraphy and angiography demonstrated improved pulmonary perfusion. At 1-year follow-up, all patients were alive and the pulmonary artery pressure estimated by Doppler echocardiography was <30 mm Hg. CONCLUSIONS: The incidence of right heart thrombus is low in patients admitted for acute PE. Thrombolytic therapy with rt-PA appears to be rapidly effective in most patients with MRHT. The thrombus usually resolves and pulmonary perfusion is rapidly improved. Systematic echocardiogram appears to be useful for rapidly detecting MRHT in patients with suspected massive PE.     

A new thrombolytic regimen for acute myocardial infarction using combination half dose tissue-type plasminogen activator with full dose streptokinase: a pilot study. KAMIT Study Group

Because a previous study utilizing a combination of recombinant tissue-type plasminogen activator (rt-PA) and urokinase demonstrated reduced reocclusion rates compared with rates obtained with rt-PA alone, this study was conducted to determine whether the combination of rt-PA and streptokinase might achieve similar results at reduced cost. Forty patients with acute myocardial infarction were treated with a 1 h infusion of rt-PA (50 mg) and streptokinase (1.5 million U) administered within 6 h (mean 3.6 +/- 1.2) of symptom onset. Emergency coronary arteriography revealed patency of the infarct-related artery in 30 (75%) of 40 patients. With the addition of coronary angioplasty in those who had unsuccessful thrombolytic reperfusion, the early patency rate was increased to 98%. In-hospital mortality rate (2.5%) and the incidence of significant bleeding requiring transfusion (15%) were low. Angiographically documented reocclusion of the infarct vessel occurred in 3 (8%) of 37 patients by day 7. Regional wall motion of the infarct zone improved by 0.9 +/- 0.9 SD/chord (p less than 0.0005), and ejection fraction increased 3.6 +/- 8% units (p less than 0.05) between immediate and day 7 studies. In contrast to the price of full dose rt-PA ($2,300) or rt-PA with urokinase ($3,500), the cost of this regimen was $1,230. This pilot study demonstrates that at half the cost, a combination of half dose rt-PA with full dose streptokinase offers high infarct vessel patency, recovery of ventricular function, a low rate of reocclusion and few bleeding complications.(ABSTRACT TRUNCATED AT 250 WORDS)     

Safety and efficacy of thrombolytic therapy for superior vena cava syndrome

The experience at the Cleveland Clinic from 1982 to 1990 using thrombolytic therapy for superior vena cava (SVC) syndrome was retrospectively reviewed. Sixteen patients, 11 of whom had indwelling central venous catheters, were treated with either urokinase (n = 11) or streptokinase (n = 5). Either urokinase (4,400 U/kg bolus followed by 4,400 U/kg/h) or streptokinase (250,000 U bolus followed by 100,000 U/h) was used, and venograms were performed before and after. Overall, 56 percent of patients had complete clot lysis and relief of symptoms. Thrombolytic therapy was effective in eight (73 percent) of 11 patients receiving urokinase and one (20 percent) of five patients receiving streptokinase. Of those with a central venous catheter, eight (73 percent) of 11 patients were successfully lysed, whereas only one (20 percent) of five patients was successfully lysed if no catheter was present. If thrombolytic therapy was performed less than or equal to five days of symptom onset, seven (88 percent) of eight patients were successful, if thrombolytic therapy was performed greater than five days after symptom onset, two (25 percent) of eight patients were successful. Symptoms were relieved and the catheter was preserved in patients in whom thrombolytic therapy was effective. Factors predicting success were as follows: (1) the use of urokinase compared with streptokinase; (2) the presence of a central venous catheter; and (3) a duration of symptoms less than or equal to five days.     

Intrapulmonary artery infusion of urokinase for treatment of massive pulmonary embolism: a review of 26 patients with and without contraindications to systemic thrombolytic therapy.

BACKGROUND: Pulmonary emboli (PE) are a common event seen in over 600,000 patients a year. Occurring suddenly, PE often result in a high rate of mortality. To combat the high rate of mortality, more aggressive therapies including the use of thrombolytics are often indicated. The use of intrapulmonary artery infusion of urokinase has been shown to promote rapid resolution of emboli and restoration of normal pulmonary hemodynamics. HYPOTHESIS: The study was undertaken to review the effectiveness and safety of pulmonary artery infusion of urokinase in 26 patients with and without contraindications to the use of systemic thrombolytic therapy. METHODS: We reviewed the outcomes of 26 patients who received infusion of urokinase, using a usual loading dose of 4,000 U/kg body weight given as a bolus, followed by 4,000 U/kg/h for 12 to 24 h, using either/or unilateral or bilateral infusions. Pulmonary angiograms were obtained prior to and following the urokinase infusions. RESULTS: Intrapulmonary artery infusion of urokinase was given to 26 patients, 9 of whom had contraindications to the use of systemic thrombolytic therapy. Six patients were recent post operative, one was receiving oral anticoagulants, one was receiving chemotherapy with bleeding complications, and one had received cardiopulmonary resuscitation. Twenty of the patients returned to their baseline state (normal heart rate, blood pressure, and p02), one was minimally improved, and five deaths occurred. Of the five deaths, three occurred within 1 h of starting urokinase infusion, the remaining two died more than 36 h after treatment with urokinase as a result of their basic underlying disease. Minor bleeding occurred from puncture sites, two hematomas occurred at the puncture site, and there were two gastrointestinal bleeds, one of which occurred a week post urokinase therapy while the patient was receiving heparin and coumadin. No central nervous system bleeds occurred and no transfusions were required as a result of urokinase intrapulmonary artery infusions. The overall mortality rate in this series was 11.5%. CONCLUSIONS: Intrapulmonary artery infusion of urokinase in extensive pulmonary embolism is a safe and efficient treatment in patients with and without contraindication to the use of systemic thrombolytic therapy. With a usual loading dose of 4,000 U/kg body weight, followed by an infusion of 4,000 U/kg/h for 12 to 24 h, it produces significant and rapid resolution of pulmonary emboli with a low morbidity and mortality rate. In our series, the mortality rate was 11.5%, and none of the deaths was the direct result of urokinase therapy.     

Accelerated plasminogen activator dose regimens for coronary thrombolysis. The TAMI-7 Study Group.

To determine the clinical profile and efficacy of accelerated recombinant tissue-type plasminogen activator (rt-PA) dose regimens, five different strategies of thrombolytic therapy in a total of 232 patients were systematically evaluated in the setting of acute myocardial infarction. The fifth strategy involved a combination of accelerated rt-PA and intravenous urokinase (regimen E). A weight-adjusted dose of 1.25 mg/kg body weight of tissue plasminogen activator over 90 min (regimen C) yielded the highest coronary patency rate (83%) at acute angiography. The associated in-hospital reocclusion rate for this regimen was low (4%). An exaggerated (60-min) dosage regimen yielded an inferior coronary patency rate (63%). Combination therapy (regimen E) was associated with a 72% patency rate and 3% reocclusion rate. Marginal improvement in global ejection fraction and regional wall function was demonstrated with all strategies by predischarge catheterization. Bleeding complications were most common at the periaccess site and were not different from those in previous experiences reported with conventional 3-h dosing regimens. Measurements of baseline, 30-min and 3-h levels of tissue plasminogen activator, fibrinogen and fibrin(ogen) degradation products were obtained. At 3 h, fibrinogen levels of less than 1 g/liter were demonstrated with combination therapy (regimen E) as well as with regimen C. Major clinical outcomes including death, reocclusion and reinfarction also showed a tendency to be less common with regimen C. Therefore, although accelerated dose regimens of rt-PA do not reliably yield acute coronary patency rates greater than 85%, an acute coronary patency rate of approximately 85% can be approached.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of intravenous urokinase plus heparin versus heparin alone in acute myocardial infarction. Urochinasi per via Sistemica nell'Infarto Miocardico (USIM) Collaborative Group

In a randomized trial of the effects on in-hospital mortality of intravenous urokinase plus heparin versus heparin alone, 2,531 patients with acute myocardial infarction in 89 coronary care units were enrolled for greater than 30 months. Patients admitted within 4 hours of the onset of pain were randomized to receive either intravenous urokinase (a bolus dose of 1 million U repeated after 60 minutes) plus heparin (a bolus dose of 10,000 U followed by 1,000 IU/hour for 48 hours) or heparin alone (infused at the same rate). Complete data were obtained in 2,201 patients (1,128 taking urokinase and 1,073 taking heparin). At 16 days, overall hospital mortality was 8% in the urokinase and 8.3% in the heparin group (p = not significant). Among patients with anterior infarction, mortality was 10.3% in the urokinase and 13.9% in the heparin group (p = 0.09; relative risk = 0.73). The incidence of major bleeding (urokinase 0.44%, heparin 0.37%) as well as the overall incidence of stroke (urokinase 0.35%, heparin 0.20%) was similar in the 2 groups. The rates of major in-hospital cardiac complications (reinfarction, postinfarction angina) were also similar.     

Hemodynamic course during fibrinolysis in severe pulmonary embolism

Seventy seven cases of severe pulmonary embolism (Miller index greater than 13 points) including 61 acute (under 5 days) and 16 subacute episodes, underwent continuous haemodynamic monitoring during treatment with either urokinase 2 000 U/kg/h for 24 hours with heparin (Group I: 18 patients), or urokinase 4 500 U/kg/h for 12 hours without heparin (Group II: 47 patients), or with streptokinase 2 00 000 U over 10 hours (Group III: 12 patients). Efficacy was defined as greater than 20% improvement of Miller index at control angiography after 48 hours (Group I: 10 patients, Group II: 31 patients, Group III: 8 patients). In the 49 patients (63%) with good results, the Miller index fell by about 50% with a significant increase in cardiac index (20%) from the 12th hour. There was a concomitant fall in pulmonary systolic arterial pressure (35%). In the 28 patients (37%) with partial improvement a 20% increase in cardiac index and an 18% fall in pulmonary systolic arterial pressure were observed only in the high dose urokinase group, despite incomplete pulmonary revascularisation demonstrating the vasodilator effect of this protocol. Fibrinolysis was repeated in the patients with incomplete results or a Miller index of over 13 points, leading to improvement in 78% of patients. Accelerated lysis of pulmonary embolism leads to rapid normalisation of haemodynamic parameters and improves the prognosis of massive pulmonary embolism by reducing the number of recurrences and the mortality rate (4%).     

病态肥胖肺栓塞患者肝素抗凝剂量的探讨（病例报告及文献复习）

目的：探讨病态肥胖肺栓塞患者抗凝治疗时普通肝素的治疗剂量。方法报告1例病态肥胖(体质量>100 kg,体质量指数>40 kg/m2)的肺栓塞患者,并进行文献复习,结合本患者和文献资料分析肝素抗凝治疗过程中肝素初始剂量、维持剂量与体质量的关系。结果患者男,21岁,身高178 cm,体质量140 kg,因“晕厥3 h”入院,肺动脉 CT 血管造影确诊为急性肺栓塞。立即按校正体质量106 kg [(实际体重+理想体重)/2]给予负荷剂量普通肝素80 U/kg,续以18 U·kg-1·h-1持续泵入,4 h 后查活化部分凝血活酶时间(APTT)为145 s;暂停肝素泵入1 h,复查 APTT 为96 s;继续暂停肝素泵入1 h,APTT 为56 s;开始以1500 U/h 泵入肝素,根据 APTT 值调整肝素泵入速度,最终肝素维持用量为9.4~14.6 U·kg-1·h-1(按校正体质量计算),APTT 维持在45~96 s。复习文献：病态肥胖患者肝素按 Raschke 量表负荷和维持治疗,会出现 APTT 超标和达标时间延长。按照校正体质量′[理想体质量+0.3×(实际体质量-理想体质量)]计算,80 U/kg 为负荷剂量,13 U·kg-1·h-1为维持剂量,可能能减少病态肥胖患者肝素治疗时 APTT 的超标几率,增加安全性。结论肝素抗凝时 Raschke 量表不适合病态肥胖肺栓塞患者,应适当降低肝素的负荷剂量和维持剂量。     

Randomized angiographic trial of recombinant tissue-type plasminogen activator (alteplase) in myocardial infarction. RAAMI Study Investigators.

Clot dissolution with restoration of infarct-related artery blood flow is the likely mechanism for the improved prognosis and mortality reduction seen after thrombolytic therapy of acute myocardial infarction. A pilot study has suggested that 100 mg of recombinant tissue-type plasminogen activator (rt-PA) infused over 90 min may lead to higher patency rates than the current standard of 100 mg over 3 h. In this multicenter, randomized, open label trial, 281 patients with acute myocardial infarction receive 100 mg of rt-PA according to either the standard 3-h infusion regimen (an initial 10-mg bolus followed by 50 mg for the 1st h, then 20 mg/h for 2 h) or an accelerated 90-min regimen (15-mg bolus followed by 50 mg over 30 min, then 35 mg over 60 min). All patients also received intravenous heparin and oral aspirin during and after rt-PA infusion. At 60 min after initiation of the rt-PA infusion, the observed angiographic patency rates were 76% (95% confidence intervals 65% to 84%) in the accelerated regimen group and 63% in the control group (52% to 73%, p = 0.03). At 90 min these rates were 81% (73% to 87%) and 77% (68% to 84%), respectively (p = 0.21). Both randomized groups experienced similar rates of recurrent ischemia, reinfarction, angiographic reocclusion, other complications of myocardial infarction (including stroke and death) and bleeding complications.(ABSTRACT TRUNCATED AT 250 WORDS)     

AngioJet rheolytic thrombectomy versus local intrapulmonary thrombolysis in massive pulmonary embolism: a retrospective data analysis.

PURPOSE: To compare the efficacy of full-dose local intrapulmonary thrombolysis (LIT) versus AngioJet rheolytic thrombectomy (ART) in the treatment of massive pulmonary embolism. METHODS: A retrospective review was conducted of 8 consecutive patients (5 women; mean age 66.0+/-5.9 years, range 56-74) who underwent LIT with high-dose intrapulmonary urokinase (4400 IU/kg over 10 minutes followed by a 2000-IU/kg/h infusion) and a subsequent 6 consecutive patients (4 men; mean age of 59.2+/-17.0 years, range 26-69) who underwent ART plus adjunctive low-dose urokinase infusions (100,000 IU) until hemodynamic recovery was achieved. Pre and postprocedural Miller scores were calculated, and relative Miller score improvement, total urokinase doses, and duration of therapy were compared. RESULTS: Hemodynamic stability was restored in all 8 LIT patients and in 5 (83%) of the 6 ART patients; 1 (16.7%) patient died during the ART procedure due to recurrent MPE. In the LIT group, the mean Miller score prior to intervention was 17.38+/-2.67, which was reduced to 6.13+/-1.46 after the intervention (p<0.0001) compared to scores of 18.83+/-2.86 and 6.83+/-2.79, respectively, in the ART group (p<0.0001). The mean urokinase dose was 2.07+/-0.44 million IU in the LIT group versus 0.70+/-0.36 million IU in the ART group (p<0.0001). The mean duration of therapy was 11.45+/-2.94 hours in the LIT group versus 3.37+/-1.41 hours in the ART group (p<0.0001). No significant difference in relative Miller score improvement was observed. CONCLUSION: By accelerating the fragmentation of thrombus, ART plus adjunctive low-dose urokinase seems to be more rapidly effective compared to LIT. ART achieves both rapid cardiovascular relief and reduces the dose of thrombolytic agent necessary in patients with massive pulmonary embolism.     

Comparative Efficacy of a Two-Hour Regimen of Streptokinase Versus Alteplase in Acute Massive Pulmonary Embolism: Immediate Clinical and Hemodynamic Outcome and One-Year Follow-Up

Objectives. This study sought to compare the efficacy of 2-h regimens of alteplase and streptokinase in acute massive pulmonary embolism. The primary end point was immediate hemodynamic improvement, and secondary end points included early clinical efficacy and safety, as well as 1-year clinical outcome.Background. Several thrombolytic regimens have been compared for the past 10 years in randomized studies, showing that 2-h infusion regimens of alteplase or urokinase lead to faster hemodynamic improvement than former 12- to 24-h administration protocols in acute massive pulmonary embolism. Many trials have focused on immediate hemodynamic and angiographic outcomes, but none has addressed long-term follow-up after thrombolysis.Methods. Sixty-six patients with acute massive pulmonary embolism (Miller score >17 and mean pulmonary artery pressure >20 mm Hg) were randomly assigned to receive either a 100-mg 2-h infusion of alteplase (n = 23) or 1.5 million IU of streptokinase over 2 h (n = 43). In both groups, heparin infusion was started at the end of thrombolytic infusion and adapted thereafter. Total pulmonary resistance was monitored over a 12-h period. Pulmonary vascular obstruction was assessed 36 to 48 h after thrombolytic therapy. One-year follow-up information included death, cause of death, recurrent pulmonary embolism, chronic thromboembolic pulmonary hypertension, stroke and bleeding.Results. Both groups had similar baseline angiographic and hemodynamic characteristics of severity, with maintained cardiac output in 64 (97%) of 66 patients. The results (mean ± SD) demonstrated that despite a faster total pulmonary resistance improvement observed at 1 h in the alteplase group compared with the streptokinase group (33 ± 16% vs. 19 ± 16%, p = 0.006), a similar hemodynamic efficacy was obtained at 2 h when both thrombolytic regimens were completed (38 ± 18% vs. 31 ± 19%). There was no significant difference in either pulmonary vascular obstruction at 36 to 48 h or bleeding complication rates. One-year event-free survival was similar in both groups, as most events were related to concomitant diseases.Conclusions. These results suggest that a 2-h regimen of streptokinase can be routinely used in patients with massive pulmonary embolism and maintained cardiac output without obviously compromising efficacy or safety.     

Coronary reperfusion studies with pro-urokinase in acute myocardial infarction: evidence for synergism of low dose urokinase

Pro-urokinase is a single chain precursor of two chain urokinase, which has been shown to induce fibrin-selective plasminogen activation. In the present study, thrombolytic efficacy of 9 million U of glycosylated pro-urokinase administered intravenously was compared with that of a combined regimen utilizing 4.5 million U of pro-urokinase and 0.2 million U of urokinase. Seventy-five patients with a first myocardial infarction were randomized to receive high dose pro-urokinase (n = 40, group A) or the combination therapy (n = 35, group B). Reperfusion of the infarct-related artery was assessed by repeat coronary angiography. Thrombolysis in Myocardial Infarction trial (TIMI) grade II or III reperfusion was achieved in 73% of group A patients compared with 66% of group B patients (p = NS). A trend toward faster reopening of the infarct-related artery was observed in patients in group B. Coronary artery reocclusion occurred in 5 (10%) of 49 patients in whom angiography was repeated within 36 h after the start of therapy. Clot-selective thrombolysis was indicated by a minimal fibrinogen decline (15% and 13%, respectively, in groups A and B). Alpha 2-antiplasmin levels, however, decreased more rapidly in patients in group B (p less than 0.05). This finding and the equivalent reperfusion rate in the combined treatment group strongly suggest synergistic interaction between these two thrombolytic agents. In summary, the high incidence of reperfusion, the low rate of early reocclusion and the paucity of side effects, particularly with regard to bleeding complications, indicate that pro-urokinase possesses the characteristics of an ideal thrombolytic agent.     

Clinical validity of a normal perfusion lung scan in patients with suspected pulmonary embolism

The objective of this study was to test the safety of withholding anticoagulant therapy in patients with clinically suspected pulmonary embolism who have normal perfusion lung scans, regardless of the clinical manifestations. Anticoagulant therapy was withheld or withdrawn in 515 consecutive patients except in patients in whom deep-vein thrombosis was detected. Only three of the 515 patients had symptomatic venous thromboembolism on follow-up. The frequency of symptomatic pulmonary embolism on follow-up was one of 515 patients. With knowledge of the normal findings by perfusion scanning, an alternative diagnosis was established in 367 of the 515 patients. Cause of symptoms remained uncertain in 148 patients. It is safe to withhold anticoagulant therapy in patients with suspected pulmonary embolism and normal perfusion scans, regardless of the clinical manifestations. The finding of a normal perfusion scan excludes the presence of clinically important pulmonary embolism and makes pulmonary angiography unnecessary.