Benefit of intrapleural fibrinolytic therapy in the treatment of complicated parapneumonic effusion and empyema.

Our study aimed to assess the benefit of intrapleural fibrinolysis before resorting to surgery to treat complicated parapneumonic effusion and empyema. We conducted a retrospective and descriptive study, including all patients hospitalized in the intensive care unit (ICU) of the Abderhaman Mami hospital, Tunisia for empyema treated with instillation of intrapleural fibrinolytic therapy between the 1st January 2000 and 31st December 2016. In all patients, empyema was diagnosed on clinical features, imaging findings (chest X-ray, thoracic echography and/or computed tomography (CT), and microbiological data. The fibrinolytic agent used was streptokinase. The efficiency of intrapleural fibrinolytic therapy was judged on clinical and paraclinical results. Among 103 cases of complicated parapneumonic effusion and empyema, 34 patients were included. The mean age was 34 years [15-81] with a male predominance (sex ratio at 2.77). Median APACH II score was 9. Fifty (50%) of the patients (n=17) had no past medical history; addictive behavior was described in 17 patients (50%). All patients were admitted for acute respiratory failure and one patient for septic shock. Pleural effusion was bilateral in 7 patients. Bacteria isolated were Streptococcus pneumonia (6 cases), Staphylococcus aureus (3 cases, including one which methicillin-resistant), Staphylococcus epidermidis (1 case), anaerobes (5 cases), and Klebsiella pneumoniae (1 case). First-line antimicrobial drug therapy was amoxicillin-clavulanate in 20 patients. A chest drain was placed in all cases in the first 38 hours of ICU admission. The median number of fibrinolysis sessions was 4 [2-9] and the median term of drainage was 7 days [3-16]. No side effects were observed. Video-assisted thoracoscopic surgery was proposed in 5 patients. The median length of hospitalization stay was 15 days [6-31]. One patient died due to multi-organ failure.

Streptokinase irrigation through a percutaneous catheter helps decrease the need for necrosectomy and reduces mortality in necrotizing pancreatitis as part of a step-up approach.

BACKGROUND: Percutaneous catheter drainage in pancreatic necrosis with a predominant solid component has a reduced success rate. To improve the efficacy of percutaneous catheter drainage, we used streptokinase in the irrigation fluid in the present study. METHODS: In this retrospective analysis of 4 prospective randomized studies performed at our center from 2014 to 2019, 108 patients were evaluated. We assessed the safety, feasibility, and efficacy of streptokinase irrigation compared to saline irrigation. Data were also analyzed between 50,000 IU and 150,000 IU streptokinase. RESULTS: There were 53 patients in the streptokinase irrigation group and 55 in the saline irrigation group, and both groups were comparable in terms of age, sex, etiology, APACHE II score, and percutaneous catheter drainage characteristics. The modified computerised tomography severity index and modified Marshall score at the onset of pain were significantly higher in the streptokinase group. Sepsis reversal was significantly higher in the streptokinase group (75% vs 36%), and the need for necrosectomy (34% vs 54%) was also lower in the streptokinase group. Mortality was lower in the streptokinase group than in the saline group (32% vs 40%). The incidence of bleeding in the streptokinase group was lower than that in the saline group (7% vs 18%). A higher dose of streptokinase (150,000 IU) resulted in lower rates of necrosectomy, bleeding, and mortality compared to those with 50,000 IU streptokinase. CONCLUSION: Significant reductions in the need for surgery and sepsis reversal were noted in the streptokinase group. The results using 150,000 IU streptokinase were superior to those using 50,000 IU streptokinase.

Comparison of QT dispersion in patients with ST elevation acute myocardial infarction (STEMI) before and after treatment by streptokinase versus primary percutaneous coronary intervention (PCI).

BACKGROUND: QT dispersion (QTD) represents inhomogeneous ventricular repolarization such that an increased QTD may predispose the heart to malignant ventricular arrhythmias (VAs). This study was conducted to compare QTD in patients with ST-elevation myocardial infarction (STEMI) before and after treatment by streptokinase (SK) versus primary percutaneous coronary intervention (PCI). METHODS: The present case-control study was conducted on 185 STEMI patients who received SK (115 cases) or underwent primary PCI (70 cases). QTD and QT corrected dispersion before and 24 h after treatment. Likewise, they were also found to correct fatal arrhythmias (VT and VF) during the first 24 h after admission, and ejection fraction (EF) 24 h after treatment was evaluated. RESULTS: QTD decreased in the primary PCI group, though no significant difference was seen between the two studied groups (P > 0.05). A significant increase was detected in the EF mean values for the primary PCI-treated patients (P = 0.022). Moreover, there was a significant reduction in QTD of patients with fatal arrhythmias in the primary PCI group (P = 0.022). CONCLUSION: An overall QTD reduction in the primary PCI group and a significant decrease in QTD of patients with fatal arrhythmias in the primary PCI group show that this treatment strategy is more efficient than thrombolytic therapy. As an important indicator of proper myocardial function, EF can independently predict improved myocardial function in the primary PCI group.

Preparation of PEG-grafted chitosan/streptokinase nanoparticles to improve biological half-life and reduce immunogenicity of the enzyme.

Streptokinase, as a thrombolytic drug, is widely used in treatment of cardiovascular disorders and deep vein thrombosis. Streptokinase is immunogenic due to its prokaryotic source, having short biological half-life (i.e. 15 to 30 min) that is not enough for an efficient therapy. In this study, nanoparticles (NPs) of chitosan/streptokinase and polyethylene glycol (PEG)-grafted chitosan/streptokinase were prepared by polyelectrolyte complex method. Particle size of chitosan and PEG-grafted chitosan NPs were 154 ± 42 and 211 ± 47 nm, respectively. Results showed that using PEG in preparation of nanoparticles leads to ~24% decrease in encapsulation efficiency. Encapsulation of streptokinase in the NPs also resulted in a slight reduction in enzymatic activity. However, in vivo findings indicated that response of the immune system was delayed for 20 days and blood circulation time of the enzyme increased up to 120 min by using PEG. Biological half-life of the drug also increased up to twice in PEG-grafted chitosan. In conclusion, PEG-grafted chitosan NPs could be an alternative for delivery of streptokinase to reduce its clinical limitations.

[Thrombolysis in pulmonary embolism with high mortality risk: Experience of a cardiology department in sub-Saharan Africa]. / La thrombolyse dans l'embolie pulmonaire à haut risque de mortalité : expérience d'un service de cardiologie d'Afrique Subsaharienne.

INTRODUCTION: High-risk pulmonary embolism (PE) accounts for 5% of total acute PE and is a life-threatening emergency requiring immediate therapeutic management by fibrinolysis. The objective of this work is to describe the experience of thrombolysis in high-risk PE in a cardiology department in Togo. PATIENTS AND METHODS: This is an analytical and descriptive study carried out in the cardiology department of the Campus teaching hospital of Lomé over a period of 5 years (August 2012 to July 2017) concerning patients hospitalized for high-risk mortality PE and having undergone streptokinase thrombolysis. RESULTS: Twenty-eight of the 102 PE were at high risk of mortality (27.5%). They were 9 men and 19 women with an average age of 61.9±14.1 years. The mean systolic blood pressure was 65mmHg and 50% of the patients were placed on dobutamine. Thrombolysis was performed in 22 of the 28 patients (78.6%). Eighteen patients had a short protocol and 4 a long protocol. The mortality rate was 32.1% or 13.6% in the thrombolysis PE versus 100% in the non-thrombolysis PE (P=0.01). Causes of death in thrombolysis were persistent shock (2 cases) at the end of thrombolysis and sudden death occurred 1 month after hospitalization. The average hospital stay was 18.8 days. CONCLUSION: The high-risk PE remains today a pathology burdened with heavy mortality. Thrombolysis remains the first treatment to reduce this mortality.

Pediatric empyema thoracis: What has changed over a decade?

OBJECTIVES: The purposes of this paper are to study clinicobacteriological profile, treatment modalities and outcome of pediatric empyema thoracis and to identify changes over a decade. DESIGN: This is a retrospective study. SETTING: Department of Pediatrics of a tertiary care hospital in North India. PATIENTS: We enrolled 205 patients (1 month-12 years) of empyema thoracis admitted over 5 years (2007-11) and compared the profile with that of a previous study from our institute (1989-98). RESULTS: Pleural fluid cultures were positive in 40% (n = 82) cases from whom 87 isolates were obtained. Staphylococcus aureus was the most common isolate (66.7%). Methicillin-sensitive S. aureus accounted for 56%, Methicillin-resistant S. aureus (MRSA) 10% and gram-negative organisms 18.3% of isolates. Intercostal drainage tube (ICDT) was inserted in 97.5%, intrapleural streptokinase was administered in 33.6%, and decortication performed in 27.8% cases. Duration of hospital stay was 17.2 (±6.3) days, duration of antibiotic (intravenous and oral) administration was 23.8 (±7.2) days and mortality rate was 4%. In the index study (compared with a previous study), higher proportion of cases received parenteral antibiotics (51.7% vs. 23.4%) and ICDT insertion (20.5% vs. 7%) before referral and had disseminated disease (20.5% vs. 14%) and septic shock (11.2% vs. 1.6%), less culture positivity (40% vs. 48%), more MRSA (10.3% vs. 2.5%) and gram-negative organisms (18.4% vs. 11.6%), increased use of intrapleural streptokinase and surgical interventions (27.8% vs. 19.7%), shorter hospital stay (17 vs. 25 days) and higher mortality (3.9% vs. 1.6%). CONCLUSIONS: Over a decade, an increase in the incidence of empyema caused by MRSA has been noticed, with increased use of intrapleural streptokinase and higher number of surgical interventions.

Tenecteplase versus streptokinase thrombolytic therapy in patients with mitral prosthetic valve thrombosis.

OBJECTIVE: Prosthetic valve thrombosis (PVT) is a dreadful complication of mechanical prosthetic valves. Thrombolytic therapy (TT) for PVT is an alternative to surgery and currently making a leading role. This study compares TT with tenecteplase (TNK) and streptokinase (SK) head to head in patients with mitral PVT. METHODS: In this single center, observational study, patients with mitral PVT diagnosed by clinical data, transthoracic echocardiography, transesophageal echocardiography, and fluoroscopy were included. After excluding patients with contraindications for thrombolysis, they were randomly assigned to receive either SK or TNK regimen. Patients were monitored for success or failure of TT and for any complications. RESULTS: Among 52 episodes (47 patients with 5 recurrences) of mechanical mitral PVT, 40 patients were thrombolyzed with SK and 12 patients were thrombolyzed with TNK. Baseline characteristics including demographic profile, clinical and echocardiographic features, and valve types were not statistically significant between the groups. Complete success rate was 77.5% in SK group and 75% in TNK group (p=0.88). Partial success rate, failure rate, and major complications were not statistically significant between the two groups. Within 12h of therapy, TNK showed complete success in 33.3% of patients compared to 15% in SK group (p-value <0.02). Minor bleeding was more common in TNK group. CONCLUSION: Slow infusion of TNK is equally efficacious but more effective than SK in the management of mitral mechanical PVT. 75% to 77.5% of PVT patients completely recovered from TT and it should be the first line therapy where the immediate surgical options were remote.

Acute renal artery embolisation: role of local catheter-based intra-arterial thrombolysis.

A 45-year-old man without previous comorbidity presented to us with acute onset right-sided flank pain for last 14 hours. His general physical and systemic examination was unremarkable, and there were no clinical signs of peritonitis. The ultrasonography did not reveal any evidence of nephrolithiasis or hydronephrosis. His contrast-enhanced CT scan revealed hypoattenuated areas of right kidney and evidence of right renal artery thrombosis. He was immediately shifted to cardiac catheterisation lab, and his renal angiography showed thrombotic occlusion of right renal artery. The bolus dose of streptokinase (250 000 IU) was given locally in renal artery by right judkins catheter followed by systemic infusion of streptokinase (100 000 IU/hour) for 24 hours. After that he was started on low molecular weight heparin. Repeat renal angiography done after 5 days showed completely normal right renal artery. His cardiac and thrombophilia work up was negative, and he was discharged on antiplatelets, oral anticoagulants and statins.

Intrapleural streptokinase is effective and safe for children with multi-loculated empyema regardless of the time from disease onset.

AIM: This study compared the efficacy of administering intrapleural streptokinase to children with multi-loculated empyema within 14 days or at any time after disease onset. METHODS: We studied children under 12 years with multi-loculated empyema who were admitted to a teaching hospital in Chandigarh, India, from July 2013 to June 2017. They received antibiotics, pleural drainage and intrapleural streptokinase. The first group received three doses within 14 days of disease onset, the second received three doses regardless of time after onset and the third group received four to six doses regardless of time after onset. The three phases lasted 18, 18 and 12 months, respectively. RESULTS: Of 195 children, 133 (68%) received streptokinase within 14 days, 46 (24%) beyond 14 days and 16 (8%) did not receive it. There was no difference in surgical decortication (14/133 versus 7/46, p > 0.05) and median hospitalisation duration (15 versus 14 days, p > 0.05) between administration before versus after 14 days. Median hospitalisation was shorter with four to six doses than three doses (11 versus 16 days, p < 0.01). CONCLUSION: Intrapleural streptokinase was effective for multi-loculated empyema even when it was administered more than 14 days after disease onset and four to six doses were superior to three doses.

The Efficacy of VATS and Intrapleural Fibrinolytic Therapy in Parapneumonic Empyema Treatment.

BACKGROUND: Development of multiloculation-septation is a challenging entity in empyema patients. In this study, it is aimed to investigate the success rates of videothoracoscopic deloculation (VATS-D) and intrapleural fibrinolytic (IPFib) application after tube thoracostomy. METHODS: The study retrospectively examined the patients diagnosed with empyema with multiloculation and septation between January 2005 and December 2014. Among these patients, the study included those who received VATS-D or IPFib therapy. RESULTS: VATS-D (Group 1) was applied to 54 patients and IPFib (Group 2) was applied to 24 patients. The success of both procedures was evaluated considering the need of decortication in the following periods. In the VATS-D group, 4 (7.4%) patients required decortication via thoracotomy where it was 1 (4.1%) patient (p = 0.577) in the IPFib group. The length of hospital stay was 6.81 ± 2.55 (4-15) days in Group 1 compared to 14.25 ± 6.44 (7-27) days in Group 2 (p <0.001). CONCLUSIONS: It was demonstrated that both of the methods applied in the study have high efficacy and are preferable methods based on the general conditions of patients. Additionally, the shorter length of hospital stays in patients received VATS-D was established as a significant parameter.

Obstructive Thrombosis of Left-Sided Mechanical Heart Valves: Clinical Profile and Thrombolytic Therapy.

BACKGROUND AND AIM OF THE STUDY: Thrombosis of a mechanical prosthetic heart valve is a potentially life-threatening complication associated with a high mortality. Although thrombolytic therapy has been considered highly beneficial in this situation, very few studies have been conducted to monitor the effectiveness of such thrombolytic therapy among Asian populations. Hence, the study aim was to evaluate the clinical profile, efficacy and safety of the thrombolytic agent streptokinase (SK) in patients with obstructive thrombosis of a left-sided mechanical heart valve. METHODS: Patients (n = 30) with left-sided mechanical heart valve thrombosis (LSMHVT) who had been managed with SK during the past four years were included in this retrospective study. Clinical features such as presenting symptoms based on NYHA functional class, prosthetic valve position, oral anticoagulant compliance, International Normalized Ratio (INR) and imaging methods including fluoroscopy, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were evaluated. In addition, the effectiveness and complications of SK were analyzed. RESULTS: The majority of patients presented with advanced NYHA class (III and IV, each 40%). Obstructive thromboses were observed at the mitral prosthesis in 70% of cases, at the aortic prosthesis in 27%, and at both valves in 3%. All patients underwent TTE, but fluoroscopy was used more often than TEE. Despite compliance with oral anticoagulation therapy, a sub-therapeutic INR was observed in 40% of cases at the time of presentation. Overall, thrombolysis was successful in 80% of patients using intravenous SK, with 100% success in patients in NYHA classes I-III and 42% for NYHA class IV. Moreover, embolic complications occurred in only a small number of patients. CONCLUSIONS: In patients with obstructive thrombosis of LSMHVT, intravenous SK was effective and should be considered as first choice in patients in NYHA classes I-III, and as an acceptable alternative in those in NYHA class IV.

Liposomes for the delivery of streptokinase.

Streptokinase is an efficient thrombolytic agent used to treat thromboembolic disorders. Conventional streptokinase formulations have limited thrombolytic activity and several shortcomings because of their immunogenicity and dose-related side effects including short half-life, lack of tissue targeting and peripheral bleeding. Different liposomal formulations have been explored by researchers in order to improve thrombolytic activity of streptokinase. Liposomal formulations could improve plasma stability, retain drug for longer periods of time in the circulation and promote selective delivery to the thrombus. Side effects of conventional streptokinase formulations, such as immunogenicity and hemorrhage, can also be reduced by using liposomal carriers. In vivo therapeutic efficacy of the liposomal streptokinase has been demonstrated well in animal models. In the present review, we will discuss the potential of different liposomal carriers to improve thrombolytic efficacy of streptokinase.

An Uncommon Complication of Streptokinase: Large Spontaneous Iliopsoas Hematoma.

Streptokinase is a fibrinolytic agent that enhances plasmin activation and is used in selected patients with acute ST elevation myocardial infarction (STEMI). Similar to the other thrombolytics, a common side effect is bleeding, especially from venous puncture sites. Here, we present a case of acute anterior wall STEMI complicated by large spontaneous iliopsoas hematoma after streptokinase administration. With conservative management, the course of the disease was uneventful, and the patient was discharged with no symptom and no clinically important sequel.

Translational initiatives in thrombolytic therapy.

Once thrombi have formed as part of the pathology defining myocardial infarction, ischemic stroke, peripheral arterial disease, deep venous thrombosis or other embolic disorders, the only clinically meaningful thrombolytic agents available for reversing the thrombogenic process are various plasminogen activators. These agents are enzymes that reverse fibrin polymerization underlying the coagulation process by converting endogenous plasminogen to plasmin, which cleaves the fibrin network to form increasingly smaller protein fragments, a process known as fibrinolysis. For the most part, the major clinically used thrombolytics, tissue plasminogen activator, urokinase and streptokinase, as well as the experimentally investigated agent staphylokinase, are the products of recombinant DNA technology, which permits molecular optimization of clinical efficacy. In all cases of molecular optimization and targeting, however, the primary challenge of thrombolytic therapy remains hemorrhagic side effects, which are especially devastating when they occur intracerebrally. Currently, the best strategy to ameliorate this adverse effect is nanoparticulate encapsulation or complexation, and many strategies of this sort are being actively pursued. This review summarizes the variety of targeted and untargeted thrombolytic formulations that have been investigated in preclinical studies.

Prolonged Infusions of Low-Dose Thrombolytics in Elderly Patients With Prosthetic Heart Valve Thrombosis.

BACKGROUND: The outcomes of thrombolytic therapy (TT) in elderly patients with prosthetic valve thrombosis (PVT) have not been evaluated previously. We investigated the outcomes of low-dose and slow infusion TT strategies in elderly patients with PVT. METHODS: Twenty-seven (19 female) patients aged ≥65 years (median: 70 years, range: 65-82 years) were treated with repeated TT agents for PVT. The TT regimens included 24-hour infusion of 1.5 million units of streptokinase in 2 patients, 6-hour infusion of 25 mg recombinant tissue plasminogen activator (t-PA) in 12 patients, and 25-hour infusion of 25 mg t-PA in 13 patients. Treatment success and adverse event rates were assessed. RESULTS: The initial and cumulative success rates were 40.7% and 85.2%, respectively. Adverse events occurred in 6 (22.2%) patients including 4 (14.8%) major (1 death, 1 rethrombosis, and 2 failed TT) and 2 (7.4%) minor (1 transient ischemic attack and 1 access site hematoma) events. Higher thrombus burden (thrombus area ≥1.1 cm2 by receiver operating characteristics analysis, sensitivity: 83.3%, specificity: 85%, area under the curve: 0.86, P = .008) and New York Heart Association class (0% vs 15.4% vs 25% vs 100% for classes I-IV, respectively, P = .02) predicted adverse events. By multiple variable analysis, thrombus area was the only independent predictor of adverse events (odds ratio: 13.8, 95% confidence interval: 1.02-185, P = .04). CONCLUSION: Slow infusion of low doses of TT agents (mostly t-PA) with repetition is successful and safe in elderly patients with PVT. However, excessive thrombus burden may predict adverse events.