Lower dosage of recombinant tissue-type plasminogen activator (rt-PA) in the treatment of acute pulmonary embolism: A systematic review and meta-analysis

Background and Objective

According to US Food and Drugs Administration (FDA), 2 hour recombinant tissue plasminogen activator (rt-PA) 100 mg infusion is recommended for eligible patients with acute pulmonary embolism (PE). However,there exists evidence implying that a lower dosage of rt-PA can be equally effective but potentially safer compared with rt-PA 100 mg regimen. The aim of this systematic review and meta-analysis is to assess the efficacy and safety of low dose rt-PA in the treatment of acute PE.

Material and Method

We searched Pubmed, EMBASE, the Cochrane library and CBM Literature Database for randomized controlled trials (RCT) focusing on low dose rt-PA for acute PE. Outcomes were described in terms of changes of image tests and echocardiography, major bleeding events, all-cause death, and recurrence of PE.

Results

Five studies (440 patients) were included, three of which compared low dose rt-PA (0.6 mg/kg, maximum 50 mg or 50 mg infusion 2 h) with standard dose (100 mg infusion 2 h). There were more major bleeding events in standard dose rt-PA group than in low dose group (OR 0.33, 95%CI 0.12-0.91;P = 0.94,I² = 0%), while there were no statistical differences in recurrent PE or all cause mortality between these two groups. Two studies compared low dose (0.6 mg/kg, maximum 50 mg/2 min bolus or 10 mg bolus, ≤ 40 mg/2 h) with heparin. There was no significant difference in major bleeding events (OR 0.73, 95% CI 0.14-3.98;P = 0.72), recurrent PE or all cause mortality. No dose-related heterogeneity was found for all the included studies.

Conclusions

The results of this meta-analysis were hypothesis-generating. Based on the limited data, our systematic review suggested that low dose rt-PA had similar efficacy but was safer than standard dose of rt-PA. In addition, compared with heparin, low dose rt-PA didn’t increase the risk of major bleeding for eligible PE patients.     

Evaluation of chest tube administration of tissue plasminogen activator to treat retained hemothorax

Background

When retained hemothorax occurs, video-assisted thoracoscopy or thoracotomy is performed, but recently, tissue plasminogen activator (tPA) has been used. This study evaluated intrapleural tPA use for retained traumatic hemothoraces.

Methods

A retrospective review was conducted of trauma patients treated with intrapleural tPA for retained hemothorax. Data included demographics, past medical and surgical histories, injury details, treatment details, and outcomes.

Results

Seven patients (median age = 47 years, male = 6, blunt trauma = 6) met study criteria. All patients received a chest tube. Six patients later received computed tomography-guided drains for tPA infusion. Number of tPA treatments per patient varied from 1 to 5. Median total tPA dosage was 24 mg. Median time from injury to chest tube placement was 11 days and from chest tube placement to first tPA treatment was 4 days. No patients required a video-assisted thoracoscopy; however, 1 patient required thoracotomy. There were no deaths or bleeding complications attributed to intrapleural tPA.

Conclusion

Although future studies are needed to identify optimum treatment guidelines, intrapleural tPA appears to be a safe and efficacious treatment option.     

Adrenal gland-dependent augmentation of plasminogen activator inhibitor-1 expression in streptozotocin-induced diabetic mice

BACKGROUND: Diabetes is associated with an excess risk of cardiac events, and one risk factor for infarction is an elevated level of plasminogen activator inhibitor-1 (PAI-1). OBJECTIVES AND METHODS: To evaluate whether the glucocorticoid hormones are involved in the diabetes-induced PAI-1 production, we examined expression profiles of PAI-1 mRNA in adrenalectomized (ADX) mice with streptozotocin (STZ)-induced diabetes. RESULTS: The diabetes-induced augmentation of plasma PAI-1 levels and PAI-1 mRNA expression in the heart and lungs was completely normalized in diabetic ADX mice. The glucocorticoid receptor antagonist RU486 significantly, but only partly suppressed PAI-1 induction in STZ-induced diabetic mice, suggesting that factors other than glucocorticoids are also involved in PAI-1 induction provoked by diabetes. CONCLUSION: Our results suggested that the adrenal gland plays a critical role in the progression of thrombosis in diabetic patients by inducing expression of the PAI-1 gene.     

蛇毒蛋白C激活剂实验条件及稳定性的探讨

目的探讨可能影响蛇毒蛋白C激活剂作用的实验条件和该试剂的稳定性。方法分别采用APTT法和CBS02.46底物法，检测蛇毒蛋白C激活荆在不同实验条件下的抗凝活性及酰胺酶活性。结果蛇毒蛋白c激活剂的最适pH值为6．0～7．0，最适温度为37～40℃，肝素、枸橼酸钠等抗凝剂及Na^ 、K^ 、EDTA等不影响其活性，SDS则显著抑制其生物学活性。该试剂溶液剂型在室温下或4℃中4w内效价无变化，冻干剂型则在2y内效价无明显变化。结论蛇毒蛋白C激活剂是一种效价较高、稳定性较好，影响因素少的蛋白C活化试剂。     

Acute-phase response of human hepatocytes after infection with Chlamydia pneumoniae and cytomegalovirus

BACKGROUND: There is increasing evidence that chronic inflammation plays a pivotal role in the development of atherosclerosis. Whether inflammation is the cause or consequence of vascular damage is unclear. Also, the source of inflammation is unknown, but may well be infection by Cytomegalovirus (CMV) or Chlamydia pneumoniae (C. pneumoniae). Infection of the liver by CMV or C. pneumoniae may induce a general inflammatory reaction contributing to accelerated atherogenesis. In this study we investigated the production of interleukin-6 (IL-6), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) by hepatocytes after infection with CMV or C. pneumoniae. METHODS: HepG2 cell monolayers were grown to confluence in 48-well tissue culture plates. Hepatocytes were infected with 50 microL or 100 microL of suspension of CMV (10(2.70) TCID50 mL(-1)) and C. pneumoniae (10(4.75) TCID50 mL(-1)). The medium of the inoculated cells was collected every 24 h, from day 1 to day 4, for determination of IL-6, PAI-1 and fibrinogen concentrations. RESULTS: Fibrinogen production was increased significantly in a dose-dependent manner after infection with CMV (50 microL: P=0.022 and 100 microL: P<0.001) and C. pneumoniae (P=0.012). Cytomegalovirus infection resulted in an increase of IL-6 production compared with uninfected cells (P=0.048). Cytomegalovirus and C. pneumoniae infection did not result in a significantly increase of PAI-1 production by hepatocytes. CONCLUSION: We conclude that in addition to direct vascular wall infection by C. pneumoniae and CMV, virus-related development of atherosclerosis might also be initiated by chronic liver infection and subsequent production of inflammatory and procoagulant mediators released in the circulation. This may be another pathophysiological link for the observed relation between infections and the development of atherosclerosis.     

冠心病发病与血浆纤溶酶原激活物抑制剂-1及其基因4G/5G多态性的关系

目的 探讨冠心病患者血浆纤溶酶原激活物抑制剂-1（PAI-1）水平和活性（PAI：A）的升高与PAI-1基因4G/5G多态性的关系及其对发病的影响。方法 122例冠心病患者与172例健康对照者，同时做PAI-1基因型分析并测定PAI-1，PAI：A。结果 PAI-1基因型分布在冠心病组4G/4G型最多（47.2%)。对照组中以4G/5G型最多（49.4%)；PAI-1与PAI：A在4G/4G，5G/5G，4G/5G3种基因型组间比较差异有显著性意义。其中以4G/4G基因型组PAI-1及PAI：A最高。结论 血浆PAI-1增高，是冠心病发病的危险因素。冠心病组4G/4G基因型频率是PAI-1增高的重要影响因素，PAI-1基因4G/5G多态性可能部分地决定了冠心病发病的倾向性。