Comparison of the Effects of Streptokinase and Heparin on the Early Rate of Resolution of Major Pulmonary Embolism

The extent of early resolution of major pulmonary embolism observed in 10 patients after 24 hours of treatment with heparin was compared with that seen in 17 patients after 24 hours of treatment with streptokinase. The patients in the streptokinase group also received a loading dose of heparin and were treated with heparin by continuous infusion when their thrombin time returned to normal levels. All had pulmonary hypertension. Pulmonary embolism was classified as acute in the 10 patients in the heparin group. Seven of these patients showed no angiographic change, two showed slight improvement and one showed angiographic deterioration. There was a moderate and statistically insignificant fall in mean pulmonary arterial pressure and total pulmonary resistance. Fourteen of the 17 patients who were studied before and after streptokinase were classified as acute and three as subacute progressive major pulmonary embolism. Eight showed marked angiographic improvement, four moderate and two slight angiographic improvement. There was a moderate and statistically significant fall in the mean pulmonary arterial pressure and pulmonary vascular resistance. In addition, all seven patients in whom no angiographic improvement occurred during heparin therapy showed moderate or marked angiographic improvement after a further 24 hours of treatment with streptokinase. The results strongly suggest that streptokinase therapy accelerates thrombolysis in patients with acute major pulmonary embolism.     

Local streptokinase administration in massive pulmonary embolism

Five patients with acute massive pulmonary embolism were treated with streptokinase administered via the pulmonary artery as close as possible to the embolus. Streptokinase (Awelysin) was infused at a loading dose of 250,000 IU followed by a maintenance dose of 100,000 IU/hour under haemodynamic and angiographic control. In four of five patients (two patients with cardiogenic shock) the clinical signs, pulmonary artery pressure and the angiographic findings improved or they normalised within 5-12 hours. In one patient with recurrent embolisation over three weeks the clinical condition improved gradually, although the angiographic findings improved only slightly. The results demonstrate that local thrombolysis of acute massive pulmonary embolism is a highly effective form of treatment.     

Comparison by Controlled Clinical Trial of Streptokinase and Heparin in Treatment of Life-threatening Pulmonary Embolism

Treatment with heparin or streptokinase was allocated randomly to 30 patients with life-threatening pulmonary embolism verified by angiography. Treatment was given for 72 hours and pulmonary angiography was repeated. There was significantly greater (P < 0·001) evidence of thrombolysis in those patients treated with streptokinase compared with those treated with heparin. The reduction of systolic and mean pulmonary arterial pressures was also significantly greater (P < 0·05 and P < 0·02 respectively) in the streptokinase group.Seven patients failed to complete 72 hours of the trial treatment: five successfully underwent pulmonary embolectomy. Six of these “failures” had initial pulmonary angiographic scores of 24 or more and systemic systolic blood pressure recordings of 100 mm Hg or less. Patients with these features should probably be considered for pulmonary embolectomy as the initial treatment.A febrile reaction commonly occurred in the streptokinase group; otherwise side effects were no more common than in the heparin group.     

Comparison of Streptokinase and Heparin in Treatment of Isolated Acute Massive Pulmonary Embolism

Massive pulmonary embolism was confirmed by pulmonary arteriography in 23 patients. All were seen between 2 and 48 hours after the onset of embolism and none had pre-existing cardiorespiratory disease. Fifteen were treated with streptokinase and eight with heparin. Factors which might influence prognosis and rate of resolution were similar in the patients in each group, and there was no significant difference between the groups in terms of pretreatment haemodynamic or arteriographic findings. Haemodynamic and arteriographic findings after treatment for 72 hours provided an objective measurement of resolution, which was significantly greater in the streptokinase-treated patients. There was no mortality in either group, but treatment had to be changed in two heparin-treated patients because of clinical deterioration. The principal complication of treatment, seen more often in the streptokinase-treated patients, was bleeding from cut-down or operation sites.     

Treatment of pulmonary embolism with streptokinase. A preliminary report

Nine patients with arteriographically proved pulmonary embolism have been treated by a 36-hour infusion of streptokinase. Satisfactory haemodynamic and arteriographic resolution was obtained in four patients with acute massive pulmonary embolism and in two with recent minor embolism. Little or no haemodynamic or arteriographic improvement was obtained in three patients with pulmonary thromboembolic disease of longer duration.     

Resolution of Pulmonary Embolism

To assess restoration of pulmonary perfusion after pulmonary embolism serial lung scans were carried out on 74 patients. Of these, one-third showed almost complete recovery, one-third improved, and the remainder either failed to improve or became worse. Perfusion was most rapidly restored in the first few days after the embolus and more slowly during the next two to three weeks.Untreated patients improved less often and had more new defects in perfusion than patients treated with anticoagulant therapy, no difference occurring in either the amount of improvement or in the rate of recovery of perfusion between patients treated with different anticoagulant regimens. There was evidence of further pulmonary emboli in 35% of treated patients, 82% of these occurring within two weeks of the initial embolus. Patients with defects in perfusion greater than 30% showed considerable improvement but recovered less well than those with smaller defects.     

Streptokinase in Recent Myocardial Infarction: A Controlled Multicentre Trial

In this controlled multicentre trial treatment with either streptokinase or heparin was allocated at random to patients suffering from myocardial infarction of less than 24 hours'' duration. Treatment with either drug was standardized and lasted for 24 hours. A total of 764 patients entered the trial; 34 patient charts were rejected (including all 28 charts from one centre) because of data failure. On retrospective analysis of the 730 remaining patients the two groups were found to have been comparable at the start.The total hospital mortality was 18·5% of 373 patients allotted to streptokinase treatment and 26·3% of 357 given herapin. The mortality after infusion (24 hours) was 10·6% of 340 patients treated with streptokinase and 17·8% of 320 given herapin (P=0·011). Reinfarction in hospital after the 24-hour period of infusion occurred significantly less often in patients treated with streptokinase (P=0·036). Bleeding from puncture sites and pyrexia occurred more frequently during streptokinase treatment.After exclusion of those patients whose diagnosis was unconfirmed on retrospective assessment, the total hospital mortality rate was 19·0% of 357 patients treated with streptokinase and 27·4% of 339 treated with heparin (P=0·011). These results indicate that in recent myocardial infarction streptokinase was superior to heparin in reducing mortality and reinfarction rate during an average period of six weeks in hospital.     

Thrombolytic therapy in arterial thrombosis producing acute ischemia of the lower limbs]

Efficiency of the thrombolytic therapy in the acute arterial thrombosis (producing an acute ischemia of the lower limbs) with streptokinase has been assessed in 35 patients treated in the selected departments of vascular surgery in Poland. Complete recovery has been noted in 9 patients (25.7%) in whom limb functioning with detectable peripheral pulse have been restored. An improvement has been achieved in 12 (34.3%) patients and moderate result in 4 (11.4%) patients. The limb has been amputated in 7 (20%) patients, and 3 patients (8.6%) died. Similar results have been observed in case of ischemia of duration period below 12 hours, between 12 and 24 hours, and between 24 and 72 hours. The results have been worse when thrombolytic therapy was introduced after 72 hours.     

Heparin Prophylaxis against Fatal Postoperative Pulmonary Embolism

Low-dose heparin prophylaxis against fatal pulmonary embolism has been studied in a random and prospective trial in 300 patients over the age of 50 who underwent major surgery. A dose of 5,000 IU mucous heparin sodium given two hours preoperatively and for five days post operatively prevented fatal pulmonary embolism in all 156 patients so treated, whereas out of 144 patients in the unheparinized group 6 (4·2%) died of pulmonary embolism. This difference is statistically significant. There was no increase in operative or post-operative bleeding or in the formation of wound haematomas in the heparinized group.     

Treatment of deep vein thrombosis with streptokinase.

From September 1962 to May 1972 145 patients with acute or subacute deep vein thrombosis confirmed by phlebography were treated with streptokinase. During the same period 42 patients considered unfit for thrombolytic therapy were treated with herapin and oral anticoagulants. The results, assessed by repeat phlebography, in 93 of the patients treated with streptokinase were compared with those in 42 patients treated with heparin. The age, sex, and severity of occlusion were roughly similar in both groups. Streptokinase treatment was successful in 42 per cent, partially successful in 25 per cent, and unsuccessful in 32 per cent of the 93 patients compared with none, 10 per cent, and 88 percent respectively in the 42 patients treated with heparin. Streptokinase was more effective when the thrombus was in proximal rather than calf veins. Thrombi of more than six days old were readily lysed. Plasma fibrinogen levels were below 0-8 g/1 (80 mg/100 ml) in nearly all patients successfully treated. The incidence of pulmonary embolism was no greater with streptokinase than with heparin treatment. Only prolonged follow-up would show whether thrombolytic treatment would be effective in preventing late complications of deep vein thrombosis such as chronic venous insufficiency.     

Treatment of Acute Massive Pulmonary Embolism by Streptokinase during Labour and Delivery

A 29-year-old woman sustained an acute massive pulmonary embolism in the 32nd week of pregnancy. Rapid clinical improvement followed the use of streptokinase. Treatment was continued for 41 hours, including labour and the first three hours after delivery. There was slow but severe postpartum haemorrhage. Partial uterine atony occurred, and may have been due, at least in part, to fibrin degradation products arising from thrombolysis. No adverse effects were noted in the baby.Our experience suggests that streptokinase may be given during labour but that an oxytocic agent may be needed; and that reversal of fibrinolysis before delivery is best achieved by the use of aprotinin (Trasylol) rather than aminocaproic acid.     

Prevention of Recurrent Pulmonary Embolism

Fifty patients have been studied by bilateral phlebography following their first, or sometimes recurrent, pulmonary embolus. Nineteen were found to have fresh loose peripheral thrombus, and in eight of them the thrombus looked big enough to cause a major pulmonary artery obstruction and death. These 19 patients were treated by vein ligation in addition to anticoagulants.The incidence of recurrent embolism in the trial group is significantly lower than that found in a retrospective study of 50 patients treated with anticoagulants only. It is suggested that anticoagulants will not prevent all recurrent pulmonary emboli, and that phlebography, and if necessary surgery, should be part of the routine investigation and treatment of all patients after their first pulmonary embolus.     

43例术后疑似急性肺栓塞分析

目的:探讨影响术后急性肺栓塞(Acute Pulmonary Embolism,APE)的发生和预后的相关因素,以提高对术后肺栓塞的认识和诊疗水平。方法:收集2009.01-2014.12期间南方医院术后疑似急性肺栓塞患者的临床资料,总结其临床特征,分析其诱发因素、临床表现、治疗和预后,探讨其发病的高危因素。结果:共收集术后疑似肺栓塞43例,平均年龄56.09±14.08岁(17~80岁),明确诊断为肺栓塞15例(34.9%),共死亡20例(死亡率46.5%)。其临床表现和体征均具有非特异性,呼吸困难、心悸和晕厥是主要的临床表现。不仅可以发生于下肢、胸腹部(包括妇产科)、颅内等大手术后,也可能发生在介入栓塞术后。相关危险因素很多,包括性别、年龄、恶性肿瘤、全身麻醉、手术时间长等。具有高危因素的患者并具有可疑肺栓塞的临床表现时,结合D-二聚体、动脉血气分析、心电图、胸部X线、超声心动图、下肢彩超可检查协助APE的诊断,而胸部增强CT作为检查手段有利于明确诊断。结论:肺栓塞是手术后致命的并发症之一,早期诊断、早期治疗,能降低术后肺栓塞患者的死亡率。     

Certain aspects of acute arterial thrombosis]

An analysis included 228 patients with the acute arterial thrombosis in the extremities. Over 33% of patients reported to the treatment later than 24 hours after the onset. This delay markedly worsened the results of therapy. Sixty two percent of limbs was saved. Mortality rate was 15%. The author analyse the results of therapy in relation to the localization of thrombi and type of the treatment--surgical, use of vasodilators with heparin or streptokinase. In case of thrombosis localized in the end segment of aorta the results were less promising than in case of more peripheral arterial involvement. Excellent and favourable results in this group amounted to 32%, the limb was amputated in 13% of patients and 28% of patients died. Hundred eighty patients were operated. Arteriosclerotic lesions to the arterial wall were detected in 97%. Excellent and favourable results of surgery were achieved in 45%, amputations amounted to 22%, and mortality rate was 16%. Vasodilators combined with heparin produced an improvement in 13% of patients in whom surgery could be postponed. The best results were achieved in patients treated with fibrinolytic agents with subsequent surgery or without it. In this group excellent and favourable results amounted to 57%, amputations--24%, and mortality rate--8%.     

Tissue plasminogen activator and acute pulmonary embolism

We assessed the efficacy and safety of peripheral intravenous recombinant human tissue-type plasminogen activator (rt-PA) in 47 patients with angiographically documented pulmonary embolism (PE). We administered 50 mg/2 h and, if necessary, an additional 40 mg/4 h. By 6 hours, 94% of the patients had angiographic evidence of clot lysis that was slight in 5, moderate in 12, and marked in 27 patients. Among the 34 patients with pulmonary hypertension prior to treatment, average pulmonary artery pressure decreased from 43/17 (27) to 31/13 (19) mm Hg (P less than 0.0001). The average lung scan perfusion defect decreased from 37% before therapy to 16% (P less than 0.01) after therapy among the 19 patients who had pre- and post-treatment lung scans. Of 7 patients with pre- and post-treatment imaging and Doppler echocardiograms, hypokinetic right ventricular wall movement (mild in 1, moderate in 2, and severe in 4) normalized in 5 and improved to mild hypokinesis in 2. Right ventricular diameter decreased from 3.9 +/- 1.0 to 2.0 +/- 0.5 cm (P less than 0.005). Fibrinogen decreased 33% from baseline at 2 h and 42% from baseline at 6 h. However, patients with the greatest degree of angiographic clot lysis at 2 h had a preponderance of fibrinogenolysis over fibrinolysis, demonstrated by a lower ratio of cross-linked fibrin degradation products to fibrin(ogen) degradation products (0.14 +/- 0.09 vs. 0.54 +/- 0.82) (P less than 0.04). Among selected patients, peripheral intravenous rt-PA is associated with rapid lysis of PE, improved pulmonary perfusion, and improved right ventricular function.     

溶栓前后肺血栓栓塞症大鼠肺血管内皮细胞ICAM-1及Ps的表达

目的观察溶栓前后肺血栓栓塞症(pulmonarythromboembolism,PTE)大鼠肺血管内皮细胞上细胞间粘附分子-1(intercellularadhesion-1,ICAM-1),P-选择素(P-selectin,Ps)的变化,以此探讨溶栓治疗的影响。方法采用自体血栓回输法建立PTE模型,随机分为对照组、模型组、溶栓组。各组动物在栓塞后1、3、24、72、120h5个时间段分别处死,进行病理切片,免疫组化和原位杂交的方法检测肺血管内皮细胞上ICAM-1和Ps的蛋白及mRNA的变化。结果肺栓塞后病理可见肺动脉血栓形成,炎性反应明显。肺血管内皮上ICAM-1蛋白及mRNA表达在栓塞后3h开始增高(P<0·01),而Ps蛋白及mRNA表达在栓塞后1h开始增高(P<0·01)。溶栓治疗后,栓塞、出血、萎缩减轻,但炎性反应有所加重,肺血管内皮上ICAM-1和Ps的水平再次升高(P<0·01)。结论细胞间粘附分子-1与P-选择素均参与了大鼠肺血栓栓塞症的发病过程,溶栓治疗并未改善肺组织的炎性损伤。     

Guidelines for the use of intravenous thrombolytic agents in acute myocardial infarction. Ontario Medical Association Consensus Group on Thrombolytic Therapy.

A consensus group convened under the auspices of the Ontario Medical Association produced guidelines for the use of intravenous thrombolytic agents in acute myocardial infarction. The guidelines, updated to December 1988, include the following points. 1) Any hospital that routinely accepts the responsibility for looking after patients with acute myocardial infarction could offer thrombolytic therapy if monitoring facilities are available and if the staff are experienced in the treatment of cardiac rhythm disturbances. 2) Before treatment, all patients must be carefully screened for factors predisposing to hemorrhagic complications. 3) A physician should be clearly designated as responsible for the care of the patient receiving an infusion and be available in the event of problems. 4) For the two approved agents the usual dosages are as follows: streptokinase, 1.5 million units given over 1 hour; and tissue-type plasminogen activator (tPA), 100 mg over 3 hours, delivered as 60 mg in the first hour (of which 6 to 7 mg should be given as a bolus in the first 1 to 2 minutes) and then an infusion of 20 mg/h over the next 2 hours. 5) Intravenous thrombolytics should be considered for any patient with presumed acute myocardial infarction, as suggested by prolonged chest pain or other appropriate symptoms and typical electrocardiographic changes. Expeditious treatment is critical, since myocardial necrosis occurs within hours. 6) Emergency angiography is indicated for patients with hemodynamic compromise and no apparent response to streptokinase or tPA and in those with recurrent chest pain suggestive of acute myocardial infarction despite an apparent response to intravenous thrombolysis. Angiography before discharge is recommended for patients with postinfarction angina or evidence from noninvasive testing of significant residual ischemic risk. 7) There is insufficient evidence to choose between streptokinase and tPA on the basis of the two most important outcome measures: patient survival and myocardial preservation. More conclusive evidence comparing tPA, streptokinase and another promising agent, acylated plasminogen-streptokinase activator complex, will be available in 1989-90.     

Indications for Vena Caval Fenestration

A retrospective study of 20 patients who underwent vena caval fenestration showed that in 50% of the patients the procedure was done for prophylaxis and in 50% it was done for therapeutic reasons. After this procedure five patients had persistent leg swelling, two had deep venous thrombosis, two had pulmonary emboli and one died of a respiratory arrest. We recommend limiting the use of vena caval fenestration to those patients who have verified pulmonary embolism while adequately anticoagulated or patients who have pulmonary embolism and a major contraindication to anticoagulation.     

Subcutaneous injections and intravenous infusion of sodium salt of heparin in the treatment of thrombosis of deep veins of the lower extremities

Ninety-four patients with deep vein thrombosis of inferior limbs were randomly allocated to receive sodium heparin either by subcutaneous injections or by continuous intravenous infusion for six days. No significant difference was observed in the therapeutic efficiency as judged by phlebographic examinations and in rate of symptomatic pulmonary embolism between the two groups. There was one instance of major bleeding in the subcutaneous group. Minor bleedings occurred in 10 of the 48 patients treated with subcutaneous heparin and in 13 of the 46 patients receiving intravenous heparin. The results showed that subcutaneous injections of sodium heparin are as effective and safe as continuous intravenous infusion of this drug in the treatment of deep vein thrombosis.