Intravenous thrombolytic treatment of mechanical prosthetic valve thrombosis: a study using serial transesophageal echocardiography

OBJECTIVE

We analyzed the results of intravenous thrombolytic treatment under transesophageal echocardiographic (TEE) guidance in prosthetic valve thrombosis.

BACKGROUND

Thrombotic occlusion of prosthetic valves continues to be an uncommon but serious complication. Intravenous thrombolytic treatment has been proposed as an alternative to surgical intervention.

METHODS

In a four-year period, 32 symptomatic patients with prosthetic valve related thrombosis underwent 54 thrombolytic treatment sessions for the treatment of 36 distinct episodes. All patients had low international normalized ratio values at the presentation. Transesophageal echocardiography was performed at baseline and repeated after each thrombolytic treatment session (total 98 TEE examinations). Streptokinase was used as the initial agent with a repeat dose given within 24 h when necessary. Recurrent thrombosis was treated either with tissue plasminogen activator or urokinase.

RESULTS

The initial success after first dose was only 53% (17/32) but increased up to 88% (28/32) after repeated thrombolytic sessions upon documentation of suboptimal results on TEE examination (p < 0.01). In addition, four asymptomatic patients with large thrombi were also successfully treated with single infusion. The TEE characteristics of thrombus correlated with clinical presentation and response to lytics. Success was achieved with single lytic infusion in 40% of the obstructive thrombi as compared with 75% of the nonobstructive ones (p < 0.05). The success rates of lytic treatment were similar for mitral versus aortic valves, and for tilting disk versus bileaflet valves. Rapid (3 h) and slow (15 to 24 h) infusion of streptokinase resulted in similar success rates. However, major complications (three patients) occurred only in the rapid infusion group.

CONCLUSION

In patients with prosthetic valve thrombosis, intravenous slow infusion thrombolysis given in discrete, successive sessions guided by serial TEE and transthoracic echocardiography can be achieved with a low risk of complications and a high rate of success.     

Thrombolysis with Streptokinase During Cardiopulmonary Resuscitation: A Single Center Experience and Review of the Literature

Objective: To report our experience with use of thrombolysis with streptokinase during cardiopulmonary resuscitation of patients with cardiac arrest due to myocardial infarction. Design: A case series. Methods: Thrombolytic therapy (streptokinase) was administered during cardiopulmonary resuscitation of 4 patients with suspected myocardial infarction as the cause of cardiac arrest. Results: 3 of the 4 patients survived and were discharged from the hospital without any major complications or neurological sequela. Conclusion: Thrombolysis with streptokinase during cardiopulmonary resuscitation of patients with suspected acute myocardial infarction is associated with reduced mortality and favorable neurological outcome.     

Improved reperfusion and clinical outcome with enoxaparin as an adjunct to streptokinase thrombolysis in acute myocardial infarction. The AMI-SK study.

AIMS: To establish whether the addition of enoxaparin (a low-molecular-weight heparin) to streptokinase therapy improves early and sustained coronary patency and clinical outcome in patients with evolving myocardial infarction. METHODS AND RESULTS: A total of 496 patients with acute myocardial infarction treated with streptokinase were randomized to an intravenous bolus (30 mg) and subcutaneous injections (1mg x kg(-1), twice daily) of enoxaparin (n=253), or placebo (n=243) for 3-8 days. The median duration of treatment in both groups was 5 days. ST-segment resolution at 90 min and 180 min measured by electrocardiogram was improved in patients receiving enoxaparin. Complete, partial and no ST-segment resolution at 180 min was observed in 36%, 44% and 19% in the enoxaparin group vs 25%, 44% and 31% in the placebo group, respectively (P=0.004). Assessment of the primary end-point revealed improved TIMI-3 flow with enoxaparin vs placebo (70% vs 58%, P=0.01). Combined TIMI-2 and -3 flow was also improved (88% vs 72%, P=0.001), as was TIMI frame count (P=0.003). The triple clinical end-point of death, reinfarction and recurrent angina at 30 days was reduced with enoxaparin (13% vs 21%, P=0.03). CONCLUSION: Streptokinase in combination with enoxaparin is associated with better ST-segment resolution and better angiographic patency at days 5-10, suggesting more effective reperfusion. This was associated with a significant reduction in clinical events, indicating less reocclusion.     

小剂量重组织型纤溶酶原激活剂与尿激酶、链激酶治疗急性心肌梗死疗效观察

目的:观察小剂量重组织型纤溶酶原激活剂、尿激酶和链激酶静脉溶栓治疗急性心肌梗死的疗效及安全性。方法:112例急性心肌梗死患者随机分为纤溶酶原激活剂组40例,尿激酶组30例,链激酶组42例。分别应用重组织型纤溶酶原激活剂50mg、尿激酶75万u、链激酶75万u于30min内静脉输入。结果:小剂量加速静脉溶栓心肌梗死相关血管再通率,重组织型纤溶酶原激活剂组80%,尿激酶组53.5%,链激酶组50%。重组织型纤溶酶原激活剂组与尿激酶组、链激酶组疗效比较P<0.05。3组溶栓后出血及5周病死率比较无明显差异。结论:小剂量重组织型纤溶酶原激活剂治疗急性心肌梗死的疗效明显优于小量尿激酶和链激酶,不良反应无明显差异。     

Continuous ST- and QRS-vector changes and myoglobin release during streptokinase-treated acute myocardial infarction.

Twenty-two consecutive patients with a first myocardial infarction treated with streptokinase (SK) were compared to a group of 33 consecutive patients who did not receive SK. Age, infarct localization, duration of symptoms and infarct size, as estimated by cumulative creatine kinase (CK) release, did not differ between the two groups. Myoglobin (MG) release stopped after 5.5 +/- 3.3 h in SK-treated patients, which was 11 h earlier than in the controls (P less than 0.0001). CK release ceased after 15 +/- 7.8 h, about 13 h earlier than in the controls (P less than 0.0001). ST and QRS vector changes, registered by continuous vectorcardiography, were completed after 2.9 +/- 2.0 and 4.4 +/- 2.5 h respectively, about 2 and 4 earlier than in the controls (P less than 0.005 and P less than 0.0001 respectively). With SK, the termination of ST and QRS vector changes occurred more uniformly than corresponding vector changes in the controls, in whom a longer time interval between the termination of ST and the end of QRS vector changes was observed. With SK, the difference between the end of ST and QRS vectors decreased by about 3 h to 1.6 +/- 1.5 h (P less than 0.0001). Temporal relations between MG release and ST and QRS vector changes were similar but more uniform than in those of the reference group. In conclusion, we found that SK resulted in an accelerated and more uniform development of the infarct process, ending about 10 h after onset of therapy, compared with 20-30 h in the reference group.     

链激酶基因的分离与表达及其单克隆抗体的制备(英文)

用PCR方法从链球菌染色体基因组中分离了链激酶基因,并把它克隆到表达载体pBV220中。诱导表达后重组蛋白以包涵体的形式存在并占菌体总蛋白的60％以上。纯化后的重组蛋白的纯度达90％以上。血纤维蛋白原平板测活方法表明,重组蛋白比活性为1.3×10~5U/mg。重组链激酶蛋白免疫小鼠后获得6株分泌抗链激酶单克隆抗体的杂交瘤。把重组链激酶基因克隆至M13mp19中进行DNA序列分析,结果表明与文献报道的有区别。     

Inhibition of pulmonary tumor seeding by antiplatelet and fibrinolytic therapy in an animal experimental model

Fibrin and platelets contribute to the development of blood borne metastases by facilitating the arrest of tumor cell emboli in the microcirculation. We have previously demonstrated that the fibrinolytic agent strep-tokinase inhibits pulmonary tumor cell seeding in an animal model. To determine whether this effect was potentiated by antiplatelet therapy, a further study was performed to assess the effect of streptokinase in combination with aspirin in a similar model. The results demonstrated that aspirin did not significantly enhance the antimetastatic effect of streptokinase (median: streptokinase = 60, streptokinase + aspirin = 60.5, P = 0.79, Mann Whitney). In a second series of experiments, the antimetastatic effect of streptokinase was compared with another fibrinolytic agent, human recombinant tissue plasminogen activator (rt-PA). Fibrinolytic doses of streptokinase (30,000 units/kg) and rt-PA (5 mg/kg) significantly reduced pulmonary tumor seeding when compared with controls (median: control = 48, streptokinase = 23, P<0.01, rt-PA = 29, P < 0.001). There was no significant difference in pulmonary tumor seeding between the groups treated with streptokinase and rt-PA (P = 0.56). The clinical implications of these findings are discussed. © Wiley-Liss, Inc.     

注射用基因工程链激酶的临床药物动力学

目的:测定注射用基因工程(重组)链激酶(r-SK)在人体内的药物动力学.方法:6例急性心肌梗死患者在60min期间静脉匀速滴注r-SK 150万IU,用纤维蛋白-凝胶板方法测定血浆中r-SK的活性.结果:血浆浓度-时间曲线以一室模型拟合,Ke:(0.015±0.06 3)1/min,T_1/2:(49.57±19.70)mim;表观分布客积V:(11 637.03±9 730.24)ml;AUC:(18 198.82±16 413.74)IU·min/ml,CL:(153.96±103.09)ml/min.结论:对于治疗急性心肌梗死1h内静脉输注150万IU的r-SK是合适的.     

Early results of low dose intra-arterial streptokinase therapy in acute and subacute lower limb arterial ischaemia

Thirty-two patients with acute and subacute limb-threatening peripheral arterial ischaemia were treated with low dose intra-arterial streptokinase infusions. The mean duration of infusion was 38 h. Six patients developed pericatheter thrombosis and two had distal embolization of fragments of thrombus but in all cases these responded to repositioning the catheter and continuing the infusion. Five patients developed groin haematomata and in three of these there was evidence of a systemic fibrinolytic effect from the streptokinase with plasma fibrinogen reduced below 1 g/l. The most serious complication was perforation of the popliteal and tibial arteries which occurred on two occasions and required cessation of the infusion. Twenty-two patients (69 per cent) achieved limb salvage, eight (25 per cent) suffered a major amputation and two (6 per cent) died. The outcome was not related to the site, nature or duration of the arterial occlusion but patients with loss of sensation or paralysis of the affected limb were significantly less likely to obtain limb salvage (P = 0.001). For occlusions greater than 30 cm in length a new technique was used where the thrombus was lysed from distal to proximal in short lengths by gradual catheter withdrawal. This was successful in five out of six cases. Low dose intra-arterial streptokinase has been confirmed as an effective, relatively safe method of treatment in recent arterial ischaemia and can be recommended in situations where the results of surgery may not be favourable. In particular, patients with arterial thromboses and no distal run-off, distal and late arterial emboli, thrombosed popliteal aneurysms and patients after a failed embolectomy, have all been shown to respond to thrombolytic therapy with intra-arterial streptokinase.