Evaluation of clinical efficacy of streptokinase by comparison with the thrombolytic agent on animal model.

Cardiovascular disorders, including acute myocardial infarction (AMI), often lead to blood clot formation, impacting blood circulation. Streptokinase, a cost-effective and widely available thrombolytic agent, is crucial in treating thrombosis. This study aimed to produce streptokinase from Streptococcus pyogenes EBL-48 and compare its efficacy with heparin in an animal model. We evaluated the clot-lysing effectiveness of streptokinase produced from Streptococcus pyogenes EBL-48, emphasizing its low cost and ease of production. Streptokinase was produced using pre-optimized fermentation media and purified through ion exchange and gel-filtration chromatography. In vivo analysis involved inducing clots in a trial animal model using ferric chloride, comparing streptokinase with heparin. Ultrasonography assessed the clot-lysing activity of streptokinase. Streptokinase (47 kDa) effectively lysed clots, proving its low cost, easy production, and minimal adverse effects. Ultrasonography confirmed its fibrinolytic efficacy. These findings highlight potential as an affordable and easily produced thrombolytic agent, particularly relevant in resource-limited settings. Streptokinase efficacy and minimal adverse effects make it a promising option for thrombolytic therapy, especially in economically constrained regions. Future studies could optimize production techniques, explore different strains, and conduct clinical trials for human validation. Comparative studies with other thrombolytic agents would enhance understanding of their advantages and limitations.

Spontaneous retroperitoneal and intracranial hemorrhage following streptokinase therapy in acute myocardial infarction: An autopsy case report.

Bleeding complications following thrombolytic treatment for acute myocardial infarction (AMI) are not infrequent, among which intracranial hemorrhage is commonly reported. In contrast, retroperitoneal hematoma following the administration of thrombolytics is rarely reported in the literature. We are reporting a case of a middle-aged man, who presented with left-sided chest pain and was diagnosed with acute coronary syndrome with anterior wall ST elevation AMI. The patient was administered with thrombolytic drugs, including streptokinase and heparin. Percutaneous coronary intervention in the form of Coronary angioplasty with stent insertion was done to the left anterior descending artery, given coronary artery disease. The blood investigations showed elevated activated partial thromboplastin time and prothrombin time. The patient developed vomiting, altered sensorium, and left-sided weakness, and a non-contrast computerized tomography brain was done, which showed acute hemorrhage involving the right frontal lobe with intraventricular extension, so the ventricular drain was placed. The patient developed cardiac arrest and died on the third day. On autopsy examination, the brain showed subarachnoid hemorrhage, intraparenchymal hemorrhage over the right frontal lobe, and clotted blood in all the ventricles. A retroperitoneal hematoma of around 1500 cc was seen over the left side of the peritoneal cavity. This case highlights that although intracranial hemorrhage is a known complication after administrating thrombolytic therapy, clinicians should also be aware of the possibility of retroperitoneal hemorrhage. This case emphasizes the value of an autopsy in determining the cause of death in such situations.

Decrease of prothrombin level during thrombolysis in acute myocardium infarction.

Previously, the direct interactions of Bß26-42 fibrin residues with prothrombin were demonstrated. It was also shown that forming prothrombin complexes with E- or DDE-fragments causes non-enzymatic prothrombin activation. The direct measuring of the prothrombin level in the blood plasma of patients with acute myocardial infarction (AMI) allowed us to find a situation where such an activation can occur in vivo. Blood coagulation parameters in the blood plasma of patients with AMI were measured at 2 hours, three days, and seven days after the thrombolysis by streptokinase accompanied with intravenous administration of anticoagulants: unfractionated high molecular weight heparin (HMWH) and low-molecular-weight heparin (LMWH). The prothrombin level in the blood plasma of patients with AMI was normal before thrombolytic therapy and substantially decreased after streptokinase administration. This effect was prominent in the case of concomitant anticoagulant therapy with LMWH and was not observed when HMWH was applied. It can be explained by the fact that LMWH preferentially inhibits factor Xa, while the HMWH is an effective inhibitor of both factor Xa and thrombin. This observation suggested that the prothrombin level decrease was caused by the thrombin-like activity and possible autolysis of prothrombin by thrombin. Also, thrombolytic therapy with streptokinase caused the accumulation of fibrin degradation products (FDPs), some of which were able to bind prothrombin. The dramatic decrease of prothrombin level in the blood plasma of patients with AMI during thrombolysis allowed us to conclude the non-enzymatic prothrombin activation with the following autolysis of prothrombin that contributes to the pathology.

Safety outcomes of ticagrelor among patients with STE-ACS post streptokinase therapy-a retrospective observational study.

From the restriction of access to primary percutaneous coronary intervention, about 46% of patients with ST-elevation acute coronary syndrome (STE-ACS) received fibrinolytic therapy as a reperfusion strategy; streptokinase is frequently used in Thailand. Despite the guidelines recommending potent P2Y12 inhibitors among these patients, the data are limited, especially among patients with STE-ACS post streptokinase therapy. The study was proposed to describe factors for P2Y12 inhibitors selection and evaluate outcomes of pharmacoinvasively treated STE-ACS receiving ticagrelor compared with clopidogrel in Thailand. We performed a retrospective observational study of patients with STE-ACS post streptokinase therapy followed by percutaneous coronary intervention (PCI) with coronary stent placement and receiving ticagrelor or clopidogrel as P2Y12 inhibitor treatment from January 2017 to June 2021. The primary outcomes described factors for P2Y12 inhibitor selection and evaluated safety outcomes with inverse probability weight (IPW) adjustment. The secondary outcome was a composite of all-cause death, myocardial infarction and stroke. The median time from streptokinase therapy to initiating ticagrelor in the switch group was 25.7 (IQR, 1.9-4.4) hours. The factors related to switching from clopidogrel to ticagrelor included young age, history of coronary artery disease (CAD), dose of streptokinase and use of intravascular imaging. Any bleeding events occurred among 83 patients (41.71%) in the switch group and 83 patients (41.09%) in the no switch group (adjusted HR 1.04, 95% CI 0.75-1.44; p = 0.826). The composite of efficacy outcomes occurred in 6 patients in the switch group (3.02%) and 12 patients (5.94%) in the no switch group (adjusted HR 0.57, 95% CI 0.21-1.57; p = 0.279). Conclusion: In real practice, ticagrelor switching among patients with STE-ACS post streptokinase therapy did not differ regarding safety outcomes and composite of efficacy outcomes compared with clopidogrel.

Biologically-Relevant Staphylococcus Aureus Biofilm Phenotype Characterisation And Liability To Novel Antibiofilm Drugs.

Objectives: To characterise the biofilm matrix composition of a newly described Staphylococcus aureus biofilm phenotype. Method: This experimental study was conducted at the Faculty of Pharmacy, Helwan University, Cairo, Egypt, from January 2021 to March 2022, and comprised methicillin-resistant Staphylococcus aureus and methicillin-susceptible Staphylococcus aureus biofilm-forming clinical isolates which were allowed to construct biofilms under two distinct culture conditions; one a commonly used condition, and the other one a novel, more biologically-relevant condition. The formed biofilms were analysed for matrix composition through treatment with proteinase,sodium meta-periodate, and streptokinase. The efficacy of Cis-2-Decenoic acid and hamamelitannin on the biologically-relevant biofilms was evaluated using biofilm viability assay based on a colorimetric assay for measuring cell metabolic activity and scanning electron microscope imaging. Data was analysed using GraphPad Prism 5.01. RESULTS: Of the 58 isolates, 45(77.6%) were methicillin-resistant Staphylococcus aureus and 13(22.4%) were methicillin susceptible Staphylococcus aureus. There was significant difference in responses to streptokinase, proteinase and sodium meta-periodate (p<0.05) among the differentially-developed biofilms in methicillin-resistant Staphylococcus aureus isolates. Regarding the methicillin-susceptible Staphylococcus aureus isolates, the differentially-developed biofilms showed significantly different liabilities to streptokinase only (p<0.05). Mean biofilm inhibition for Cis-2- Decenoic acid was 54.27±27.93% and mean biofilm dispersion was 71.92±11.59% while the corresponding valuesfor hamamelitannin were 83.03±13.95% and 70.48±7.116% against the newly described methicillin-resistant Staphylococcus aureus biofilm phenotype. CONCLUSIONS: Applying biologically-relevant culture conditions on staphylococci biofilms and antibiofilm drugs is recommended.

Generation and characterization of a plasminogen-binding group A streptococcal M-protein/streptokinase-sensitive mouse line.

BACKGROUND: Streptococcus pyogenes (GAS) is a human bacterial pathogen that generates various mild to severe diseases. Worldwide, there are approximately 700 million cases of GAS infections per year. In some strains of GAS, the surface-resident M-protein, plasminogen-binding group A streptococcal M-protein (PAM), binds directly to human host plasminogen (hPg), where it is activated to plasmin through a mechanism involving a Pg/bacterial streptokinase (SK) complex as well as endogenous activators. Binding to Pg and its activation are dictated by selected sequences within the human host Pg protein, making it difficult to generate animal models to study this pathogen. OBJECTIVES: To develop a murine model for studying GAS infection by minimally modifying mouse Pg to enhance the affinity to bacterial PAM and sensitivity to GAS-derived SK. METHODS: We used a targeting vector that contained a mouse albumin-promoter and mouse/human hybrid plasminogen cDNA targeted to the Rosa26 locus. Characterization of the mouse strain consisted of both gross and histological techniques and determination of the effects of the modified Pg protein through surface plasmon resonance measurements, Pg activation analyses, and mouse survival post-GAS infection. RESULTS: We generated a mouse line expressing a chimeric Pg protein consisting of 2 amino acid substitutions in the heavy chain of Pg and a complete replacement of the mouse Pg light chain with the human Pg light chain. CONCLUSION: This protein demonstrated an enhanced affinity for bacterial PAM and sensitivity to activation by the Pg-SK complex, making the murine host susceptible to the pathogenic effects of GAS.

Comparative Efficacy and Safety of Thrombolytic Agents for Pulmonary Embolism: A Bayesian Network Meta-Analysis.

BACKGROUND: Thrombolytic agents and anticoagulants are the two classes of medication used in the treatment of acute pulmonary embolism (PE). There is continuous renewal and iteration of thrombolytic agents, and the efficacy and adverse effects of different agents have different effects on PE due to their different mechanisms of action. OBJECTIVES: The aim of the study was to evaluate the efficacy and safety of different thrombolytic agents in the treatment of all types of acute PE: hemodynamically unstable PE (massive PE) and hemodynamically stable PE (submassive PE and low-risk PE), using a network meta-analysis. METHODS: A search was conducted of the following databases: PubMed, The Cochrane Library, Embase, and Web of Science to collect randomized controlled trials (RCTs) comparing thrombolytic agents with heparin or other thrombolytic agents in patients with acute PE; the clinical outcomes included patient mortality, recurrent PE, pulmonary artery systolic pressure (PASP) after treatment, and major and minor bleeding. The measurement duration of outcome indicators was the longest follow-up period. Thereafter, a network meta-analysis was performed using a Bayesian network framework. RESULTS: A total of 29 RCTs (3,067 patients) were included, of which 6 studies (304 patients) were massive PE, 14 studies (2,173 patients) were submassive PE, 1 study (83 patients) included massive and submassive PE, and 8 studies (507 patients) were PE of unknown type. The treatment regimens included thrombolytic therapy (alteplase, reteplase, tenecteplase, streptokinase, and urokinase) and anticoagulant therapy alone. The results showed that the mortality using thrombolytic agents (except tenecteplase) was significantly lower compared with heparin. The recurrence of PE with alteplase was significantly lower compared with heparin (RR = 0.23, 95% CI, 0.04, 0.65). The PASP after using alteplase was significantly lower compared with heparin (mean difference = -11.36, 95% CI, -21.45, -1.56). Compared with heparin, the incidence of minor bleeding associated with tenecteplase was higher (RR = 3.27, 95% CI, 1.36, 7.39); compared with streptokinase, the incidence of minor bleeding associated with tenecteplase was higher (RR = 3.22, 95% CI, 1.01, 11.10). CONCLUSION: For patients with acute PE, four thrombolytic agents (alteplase, reteplase, streptokinase, and urokinase) appeared to be superior in efficacy compared with anticoagulants alone due to a reduction in mortality and no increase in bleeding risk. Alteplase may be a better choice because it not only reduced mortality but also reduced PE recurrence rate and treated PASP. Tenecteplase did not reduce mortality compared with anticoagulants alone and may not be a good choice of thrombolytic agent due to an increase in minor bleeding compared with streptokinase and anticoagulants alone. Thrombolytic drugs should be rationally selected to optimize the thrombolytic regimen and achieve as good a balance as possible between thrombolysis and bleeding.

Efficiency of targeted delivery of streptokinase based on fibrin-specific liposomes in the in vivo experiment.

Acute thrombosis has a narrow therapeutic window and remains the leading cause of morbidity and mortality, while thrombolytic therapy has limited efficacy and risk of side effects. We have developed and investigated new fibrin-specific systems for local drug delivery to increase efficiency while minimizing the side effects of streptokinase. The experiment was carried out on dogs with 2-h thrombi in the femoral artery received intravenous injections of streptokinase, liposome-bound and free streptokinase at 40/60% ratio, and immunoliposomes. The completeness of the vessel lumen restoration affected by the thrombus, and the risks of side effects were assessed. Fibrinolytic parameters (plasminogen, fibrinogen, alpha2-antiplasmin, and D-dimers levels) were measured at several time points after thrombus induction and the administration of the drug. There was a strong activation of fibrinolysis and consumption of fibrinolysis inhibitors after therapy with all liposomal forms of streptokinase. According to the ultrasound data, immunoliposomal form of streptokinase significantly reduces the degree of residual stenosis to 32% [30.5; 33.7] in 180 min after injection. The high fibrinolytic effect of liposomal forms of streptokinase is not accompanied by a sharp drop in the fibrinogen concentration in the blood compared to the native streptokinase by 60 min. The morphometric evaluation of the artery samples showed that immunoliposomal form of streptokinase induces a significant increase in the degree of free vascular lumen compared to the native streptokinase (71.3% (62.7; 77.5) vs. 47.7% (39.6; 55.7), p < 0.001). Thus, the study shows the efficacy of streptokinase-induced thrombolysis using immunoliposomal form of drug delivery system. Mechanism of action of the immunoliposomal delivery system.

Multiple Mutations on α, ß and γ Domains of Streptokinase Lead to the Generation of Highly Efficient Cysteine Analogues with Promising Features.

BACKGROUND: Streptokinase, one of the most widely used thrombolytic medicines, is a favorable protein for site-specific PEGylation as it lacks any cysteine residues in its amino acid sequence; however, any changes in the protein's structure should be carefully planned to avoid undesired changes in its function. OBJECTIVES: This study aimed to design and produce novel di/tri-cysteine variants of streptokinase from previously developed cysteine analogues, Arg45, Glu263, and Arg319, as candidates for multiple site-specific PEGylation. METHODS: Using bioinformatics tools and site-directed mutagenesis, we incorporated concurrent mutations at Arg45, Glu263, and Arg319 (carried out in our previous study) to create di/tri-cysteine variants of streptokinase proteins (SK45-319cys, SK263-319cys, and SK45-263-319cys) and evaluated their kinetic activity parameters by a colorimetric method, using H-D-Val-Leu-Lys-pNA.2HCl (S2251) as substrate. RESULTS: Based on the kinetic results, SK263-319cys with 44% enzyme efficiency increment compared to wild-type SK was the superior protein in terms of activity; as well, SK45-319cys and SK45-263-319cys showed 17 and 22% activity enhancement, respectively. Docking of the mutant streptokinase proteins with µ-plasmin demonstrated that changes in intermolecular interactions caused by amino acid substitution could be the reason for activity difference. CONCLUSION: The novel mutant proteins created in this study exhibit remarkable biological activity and may be uniquely suitable for simultaneous PEGylation on two/three domains. As well, PEGylated derivates of these variants might prove to be more proficient proteins, compared to the singlecysteine analogs of streptokinase; because of their more surface coverage and increased molecular weight.

A case of a young boy with hyper-fibrinolysis associated with natural fibrin precipitates suspected to have occurred through a novel coagulation and fibrinolysis mechanism.

An 8-year-old Japanese boy with no underlying disease presented with severe intramuscular hematoma of the hip, and was admitted for a disseminated intravascular coagulation-like state with fibrinolytic dominance. Laboratory examinations revealed severe hyper-fibrinolysis with elevated markers, markedly shortened euglobulin clot lysis time, mildly decreased prothrombin, and severely decreased fibrinogen and factor XIII. Natural fibrin precipitates rapidly appeared in citrate-treated, ethylene-diamine-tetra-acetic-treated, and heparin-treated samples, but not in argatroban-treated samples, indicating that the mechanism of thrombin and fibrin formation was Ca2+-independent. The precipitates were physically similar to thrombin-triggered plasma fibrin. A global coagulation assay revealed that thrombin generation potentials were normal throughout the clinical course, whereas plasmin generation was already detected before initiation of fibrin formation in the acute phase. This phenomenon disappeared with time. Changes in coagulation abnormalities and nature of fibrinolysis paralleled those seen in specific markers for streptococcal infections. Streptokinase was possibly involved in this disease, as SDS-polyacrylamide gel electrophoresis revealed that plasmin derived from streptokinase-plasminogen complex proteolyzed the prothrombin to approximately 35-kDa α-thrombin consisting of the A-B single chain, which was identified by NH2-terminal sequence analysis. The involvement of streptokinase-plasminogen-prothrombin caused by streptococcal infection may be one mechanism that produces marked hyper-fibrinolysis associated with natural fibrin precipitates.

Use of thrombolytic agents to treat neonatal thrombosis in clinical practice.

Among children, neonates have the highest incidence of thrombosis. Thrombolytic agents are used for the management of life and/or organ-threatening thrombosis. Literature on the efficacy and safety of thrombolytic agents in neonates is limited. We reviewed the evidence on dosing, administration, monitoring and treatment duration of tissue plasminogen activator (tPA), streptokinase and urokinase (URK) in neonates (≤ 28days). A systematic literature search was conducted of current databases from inception until 31 March 2021. The initial search yielded 6881 articles and 18 were retained for review. tPA, streptokinase and URK was utilized in 12, seven and four studies on 115, 51 and 16 patients, respectively. The dose range for tPA, streptokinase and URK was 0.01 -0.6 mg/kg/h, 50-2000 and 1000-0 000 units/kg/h, respectively, and treatment duration ranged from 30 min to 30 days. This is the first study to objectively summarize the efficacy and safety of thrombolytic agents in neonates. Overall, thrombolysis was associated with 87.9% complete or partial thrombus resolution and 7.4% recurrence risk. The bleeding risk associated with thrombolytic agents was 23.1% on pooled analysis, which is higher than other anticoagulants. Larger prospective studies are required to determine effective dosing regimens of these therapeutic drugs and further clarify their efficacy and safety. Blood Coagul Fibrinolysis 33:000-000 Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

The outcomes of reperfusion therapy with streptokinase versus tenecteplase in ST-elevation myocardial infarction (STEMI): a propensity-matched retrospective analysis in an Asian population.

Background Fibrinolysis using streptokinase or tenecteplase remains the primary reperfusion strategy for ST-elevation myocardial infarction (STEMI) in many Asian countries, including Malaysia. Comparative outcomes of these two fibrinolytic agents in the Asian population were inconclusive despite being widely used. Aim We aimed to assess and compare the outcomes of streptokinase versus tenecteplase in STEMI reperfusion of an Asian population. Method This single-centre retrospective study analysed data on STEMI patients who received fibrinolytic therapy from 2016 to 2020 in the Emergency Department of the largest tertiary hospital in Malaysia. Total population sampling was used in this study. Based on the propensity score matching, 359 patients receiving streptokinase were matched against 359 patients receiving tenecteplase by incorporating 16 variables that potentially affect mortality. 30-day mortality, stroke and major bleeding were the primary outcome measures. Results There was no significant difference in 30-day mortality between streptokinase (n = 39, 11.2%) and tenecteplase (n = 46, 13.2%) groups (p = 0.418). The rates of ischemic strokes [streptokinase (n = 1, 0.3%) versus tenecteplase (n = 3, 0.9%), p = 0.624], intracranial haemorrhage [streptokinase (n = 3, 0.9%) versus tenecteplase (n = 1, 0.3%), p = 0.624] and major bleeding [streptokinase (n = 4, 1.1%) versus tenecteplase (n = 3, 0.9%), p = 0.624], were comparable for the two groups. The incidences of failed thrombolysis were significantly higher in the tenecteplase arm. Hypotension and allergic reaction were significantly higher in the streptokinase arm. Conclusion Streptokinase and tenecteplase are fibrinolytic agents with similar efficacy and safety in STEMI reperfusion therapy in our Asian population.

Fibrinolytic Enzyme - An Overview.

Cardiovascular diseases, like coronary heart disease or artery disorders (arteriosclerosis, including artery solidification), heart failure (myocardial infarction), arrhythmias, congestive heart condition, stroke, elevated vital signs (hypertension), rheumatic heart disorder, and other circulatory system dysfunctions are the most common causes of death worldwide. Cardiovascular disorders are treated with stenting, coronary bypass surgery grafting, anticoagulants, antiplatelet agents, and other pharmacological and surgical procedures; however, these have limitations due to their adverse effects. Fibrinolytic agents degrade fibrin through enzymatic and biochemical processes. There are various enzymes that are currently used as a treatment for CVDs, like streptokinase, nattokinase, staphylokinase, urokinase, etc. These enzymes are derived from various sources, like bacteria, fungi, algae, marine organisms, plants, snakes, and other organisms. This review deals with the fibrinolytic enzymes, their mechanisms, sources, and their therapeutic potential.

Efficacy and safety of intrapleural streptokinase in tubercular empyema thoracis - old wine in new wineskin.

Tubercular empyema thoracis continues to be one of the leading causes of morbidity in low-income countries. Despite antitubercular therapy (ATT) and thoracostomy, empyema drainage is hampered by multiple septations, loculations, debris, and blood clots leading to complications. In a comparative experimental study to estimate the efficacy and safety of intrapleural streptokinase (IPSTK) in tubercular empyema, 30 cases of chronic multiloculated tubercular empyema were compared by radiological improvement by chest radiography, duration and volume of fluid drained, and degree of dyspnoea according to the modified Borg scale, depending on whether streptokinase was used or not. The former scored on all counts; we therefore conclude that intrapleural streptokinase is a safe, efficacious intervention in tubercular empyema. It decreases morbidity and reduces the need for surgery.

Fibrinspecific liposomes as a potential method of delivery of the thrombolytic preparation streptokinase.

The use of streptokinase (SK) in the clinic is limited by the lack of fibrin-specificity and the short half-life of the drug. We have developed a new dosage form of streptokinase (immunoliposome), which consists of "free" native streptokinase and "bound" encapsulated in liposomes conjugated through carboxylated dextran with fibrin-specific monoclonal antibodies FnI-3C (IgG2 class), in a ratio of 60 and 40%, respectively, and studied their physicochemical properties, pharmacokinetic parameters, and the ability of fibrin-specific liposomes with SK for targeted delivery to fibrin in an in vivo experiment. The obtained immunoliposomes had a hydrodynamic diameter of ~ 140 nm, a zeta potential of - 19.6 mV, and entrapment efficiency of 14.1%. Fluorescent labels bound to immunoliposomes with streptokinase selectively accumulated in model rat vein thrombi at sites containing fibrin in 30 min after injection. Studies of pharmacokinetic parameters showed that the administration of immunoliposomes with streptokinase to rats was accompanied by an increase in the half-life from 1.8 to 24.1 min, the time to reach the maximum concentration from 15 to 30 min, and a decrease in the elimination constant by about 13 times compared with the native streptokinase preparation. Further studies are needed to evaluate the thrombolytic efficacy a new dosage form of streptokinase in experiment in vivo.

Assessing the Efficacy and Outcomes Following Irrigation with Streptokinase Versus Hydrogen Peroxide in Necrotizing Pancreatitis: A Randomized Pilot Study.

BACKGROUND: Percutaneous catheter drainage (PCD's) are prone to blockage because of necrosum. To improve the efficacy of PCD, necrolytic agents have been used. The present study compared the use of Streptokinase with H2O2 in saline irrigation. MATERIALS AND METHODS: This is a single-center randomized pilot study (from July 2018 to Dec 2019). Patients with infected pancreatic necrosis not showing response to PCD and saline irrigation were included in the study. Patients received either Streptokinase (Streptokinase group 50,000 IU in 100 ml normal saline) or 3% H2O2 (3% H2O2 in 100 ml normal saline in 1:10 dilution). Primary endpoints were the need for surgery and mortality while secondary endpoints were hospital stay and complications attributable to necrolytic agents. RESULTS: There were 30 patients in the study, 15 in each arm. Organ failure was seen in 23 (76.6%), single organ failure was present in 11 (47%), and multi-organ failure in 12 (53%). Bleeding complications (20% in H2O2 vs 6.6% in Streptokinase), need for surgery (73% in H2O2 vs 33.3% in Streptokinase) and mortality (60% in H2O2 vs 33% in Streptokinase) were higher in H2O2 group but the difference was not significant statistically. Post-irrigation hospital stay was lesser in the Streptokinase group compared to H2O2 group but the difference did not reach statistical significance (14.1 ± 7.7 vs 19.2 ± 11.7, p = 0.09) CONCLUSIONS: Streptokinase irrigation led to a trend for reduced need for necrosectomy and mortality. H2O2 group had more bleeding complications. Post-irrigation hospital stay was lesser in Streptokinase group.

Urticaria, angioedema, and type I hypersensitivity reactions associated with fibrinolytic agents.

BACKGROUND: Several clinical trials of fibrinolytic agents have reported the occurrence of allergic reactions, in addition to hemorrhage. These reactions might worsen patient outcomes, especially by causing life-threatening type I hypersensitivity reactions, including anaphylaxis; however, there is a scarcity of data in this regard. OBJECTIVE: This study described and characterized patients with urticaria, angioedema and type I hypersensitivity reactions caused by fibrinolytic agents. METHODS: This was a retrospective study in which cases of suspected adverse drug reactions from the use of streptokinase, alteplase, and tenecteplase were evaluated over a period of 10 years at Phramongkutklao and Ratchaburi hospitals in Thailand. In addition, patient characteristics and management were assessed. RESULTS: A total of 824 patients received fibrinolytic agents due to various indications. Of 147 patients who received streptokinase, nine (6.12%) had suspected adverse drug reactions (one case of urticaria, two cases of anaphylactic shock, and six cases of hypotension). The prescription rate of alteplase was the highest, being taken by 547 patients; however, only one patient (0.18%) reported an adverse reaction, angioedema in the face and lips. Similarly, of the 130 patients who received tenecteplase, only one patient (0.77%) developed hypotension. CONCLUSIONS: All fibrinolytic agents, either nonfibrin or fibrin-specific, can cause urticaria, angioedema, and type I hypersensitivity reactions due to their mechanism of action.

Binding of the kringle-2 domain of human plasminogen to streptococcal PAM-type M-protein causes dissociation of PAM dimers.

The direct binding of human plasminogen (hPg), via its kringle-2 domain (K2hPg ), to streptococcal M-protein (PAM), largely contributes to the pathogenesis of Pattern D Group A Streptococcus pyogenes (GAS). However, the mechanism of complex formation is unknown. In a system consisting of a Class II PAM from Pattern D GAS isolate NS88.2 (PAMNS88.2 ), with one K2hPg binding a-repeat in its A-domain, we employed biophysical techniques to analyze the mechanism of the K2hPg /PAMNS88.2 interaction. We show that apo-PAMNS88.2 is a coiled-coil homodimer (M.Wt. ~80 kDa) at 4°C-25°C, and is monomeric (M.Wt. ~40 kDa) at 37°C, demonstrating a temperature-dependent dissociation of PAMNS88.2 over a narrow temperature range. PAMNS88.2 displayed a single tight binding site for K2hPg at 4°C, which progressively increased at 25°C through 37°C. We isolated the K2hPg /PAMNS88.2 complexes at 4°C, 25°C, and 37°C and found molecular weights of ~50 kDa at each temperature, corresponding to a 1:1 (m:m) K2hPg /PAMNS88.2  monomer complex. hPg activation experiments by streptokinase demonstrated that the hPg/PAMNS88.2  monomer complexes are fully functional. The data show that PAM dimers dissociate into functional monomers at physiological temperatures or when presented with the active hPg module (K2hPg ) showing that PAM is a functional monomer at 37°C.

Role of High Neutrophil Lymphocyte Ratio as an Independent Predictor of Adverse In-Hospital Outcomes in Patients with First Attack of ST-Elevation Myocardial Infarction Thrombolysed with Streptokinase.

Atherosclerosis is the pathognomic sign of ischaemic heart disease. Inflammation of the coronary artery contributes to the development of atherosclerosis. Neutrophil-to-lymphocyte ratio (NLR) has been reported to predict the risk of CAD and associated events in patients with ST-Segment elevation myocardial infarction (STEMI). This study was done to investigate the role of neutrophil-to-lymphocyte ratio (NLR) in predicting in-hospital adverse cardiac events in patients with STEMI thrombolysed with streptokinase (STK). This cross sectional descriptive type of study was conducted in the Department of Cardiology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from August, 2017 to October, 2018. The STEMI patients, thrombolysed with STK had blood samples at admission, analyzed for complete blood counts and NLR calculated. They were grouped into two, low and high NLR, taking 4.50 as cut-off value. Chi square test was used to compare rate of adverse events and death in hospital stay. Logistic regression analysis was used to estimate predictive ability of NLR for in-hospital cardiac events. A total of 87 (39.90%) patients had complications. Patients in high NLR group had higher rate of complications (48.3% vs. 22.5%, p<0.001) in hospital than those in low NLR group. Arrhythmias (21.1% vs. 9.9%, p<0.041), heart failure (27.9% vs. 14.1%, p=0.024), cardiogenic shock (16.3% vs. 4.2%, p<0.011), death (6.8% vs. 2.8%, p=0.227), re-infarction /post MI angina (4.1% vs. 0.0% p=0.084) occurred more in high NLR group. Mean NLR was significantly different between Group I and Group II (3.11±0.84 vs. 10.20±6.08, p<0.0001). Multivariate regression analysis showed NLR an independent predictor of in-hospital adverse cardiac events (p<0.0001). High on admission NLR is an independent predictor for in-hospital adverse cardiac events in patients with STEMI thrombolysed with streptokinase.