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.

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.

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.

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.

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.

Safety of thrombolytic therapy in patients with prosthetic heart valve thrombosis who have high international normalized ratio levels.

BACKGROUND AND AIM: Prosthetic valve thrombosis (PVT) is a rare but life-threatening complication of heart valve replacement. Based on the current guidelines, the treatment of a large number of these patients could be performed through the administration of thrombolytic agents. In the present study, we aim to assess the safety of thrombolytic therapy in patients with PVT who have high international normalized ratio (INR) levels. METHODS: In this study, we retrospectively analyzed outcomes of thrombolytic therapy in 65 PVT patients with different levels of INR at the time of fibrinolysis at a tertiary cardiac center. RESULTS: Mean age of patients was 51.6 ± 12.47 years. The tricuspid valve was the most common site of prosthetic valve thrombosis (64.6%). The Median (range) of INR was 2.1 (0.9-4.9). The majority of patients (50.8%) achieved a complete response following thrombolytic treatment. There were no cases of intracranial hemorrhage. Other major and minor bleedings occurred in 3 (4.6%) and 10 (15.4%) patients, respectively. No embolic stroke and systemic embolism were observed. We found no significant difference in the frequency of major (P-value = .809) and minor (P-value = .483) bleeding as well as response to thrombolytic therapy (P-value = .658) between patients with different levels of INR. Total administered dose of Streptokinase was also similar in PVT patients with or without major (P-value = .467) and minor (P-value = .221) bleeding complications. CONCLUSIONS: We concluded that there was no significant difference between PVT patients presenting with subtherapeutic and high INR levels who received thrombolytic treatments regarding both minor and major bleeding complications as well as response to thrombolysis.

Pulmonary haemorrhage following thrombolysis with streptokinase in myocardial infarction.

Pulmonary haemorrhage is a rare but a life-threatening complication of thrombolytic therapy in patients with acute ST-elevation myocardial infarction (MI). It usually presents with anaemia, massive haemoptysis, acute-onset respiratory distress and diffuse bilateral lung infiltrates on imaging. We hereby describe two patients, who had pulmonary haemorrhage following streptokinase therapy for acute MI. The first patient improved with conservative treatment, while the second patient died due to respiratory failure. Streptokinase, a fibrin non-specific agent, is a widely used thrombolytic in low-income and middle-income countries. Pulmonary haemorrhage should be suspected in patients who develop sudden respiratory compromise after receiving thrombolytics, especially streptokinase. The management issues related to this uncommon life-threatening complication have been discussed in this article.

Fibrinolysis: a Misunderstood Natural Defense Whose Therapeutic Potential Is Unknown.

Ever since tissue plasminogen activator (tPA) was approved for therapeutic fibrinolysis in 1987, it has been the fibrinolytic of choice. At the same time, it is also recognized that tPA never lived up to its clinical expectations and has more recently been replaced by percutaneous coronary intervention (PCI) as the treatment of choice for acute myocardial infarction (AMI). For other occlusive vascular diseases and for patients in remote areas, tPA remains an essential option. In view of the continued importance of fibrinolysis, it is disappointing that fibrinolysis never evolved beyond what it was when tPA replaced streptokinase (SK) 32 years ago. The endovascular procedure replacement for AMI treatment suffers from being technically demanding, time-consuming, and costly. An untested alternative fibrinolytic paradigm is that of the endogenous, physiological system, which is initiated by tPA but then is followed by the other natural plasminogen activator, urokinase plasminogen activator (uPA). In this combination, it is uPA rather than tPA that has the dominant function. This is also evident from gene knockout studies where deletion of uPA that it has the dominant effect. The fibrinolytic properties of tPA and uPA are complementary so that their combined effect is synergistic, especially when they are administered sequentially starting with tPA. Endogenous fibrinolysis functions without bleeding side effects and is ongoing. This is evidenced by the invariable presence in blood of the fibrin degradation product, D-dimer (normal concentration 110-250 ng/ml). This activator combination, consisting of a mini bolus of tPA followed by a 90-min proUK infusion, was once used to treat 101 AMI patients. Compared with the best of the tPA mega trials, this regimen resulted in an almost a doubling of the infarct artery patency rate and reduced mortality sixfold. To date, a second trial has not yet been done.

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.

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.

Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes.

Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality. METHODS: In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time-dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events. RESULTS: A total of 822 patients (4.4%) had ≥1 spontaneous ischemic event; 485 patients (2.6%), ≥1 spontaneous PLATO major bleed, 282 (1.5%), ≥1 spontaneous TIMI major bleed; and 207 (1.1%), ≥1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short- and long-term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95% CIs) for short- and long-term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and 0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P>0.05) CONCLUSIONS: In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem "prognostically equivalent" to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS.

A Comparative Study of In-Hospital Outcome of Patients with ST-Segment Elevation Myocardial Infarction with and Without Diabetes Mellitus, after Thrombolytic Therapy; In Government Hospital of Rajkot, Gujarat, India.

BACKGROUND: Diabetes mellitus is considered as a major health problem and an epidemic throughout the world. The mortality of patients with diabetes is almost twice that of non-diabetic. The outcome of in-hospital patients with myocardial infarction with and without diabetes after thrombolytic therapy is presented here. AIM: To compare the outcome of patients with myocardial infarction after thrombolysis in diabetics and non-diabetics in government hospital of Rajkot, India. METHODS: A retrospective, observational study was carried out between the period of March-2014 to April-2015. Patients who presented with acute myocardial infarction having ST-elevation as MI picture, were admitted to the emergency room of medicine department. All these patients were treated with streptokinase as a thrombolytic agent. Baseline ECG was taken on admission and the one after 60 minutes of thrombolysis. The study group involved two types: (i) diabetic (ii) nondiabetics. RESULTS: A total of 395 patients were included in the study. Out of them around 104 were females and 291 were males. ST-segment resolution in non-diabetic patients was found in 180 patients out of 186 and in diabetics it was found in 174 patients out of 208. Complications related to post fibrinolytic therapy was more prevalent in diabetics 148 patients (71.15%) as compared to those in non-diabetics 47 patients (25.26%). Mortality was observed only with diabetics (23.52%) as compared to no mortality in non-diabetics. CONCLUSION: Overall, morbidity and mortality of diabetic patients with Acute Myocardial Infarction was found to be greater as compared to non-diabetics; post thrombolysis.

Thrombolysis for Left-Sided Prosthetic Valve Thrombosis: Short- and Long-Term Outcomes.

BACKGROUND AND AIM OF THE STUDY: Emergency valve replacement has long been the treatment of choice in left-sided prosthetic valve thrombosis (PVT) for critically ill patients in NYHA classes III-IV. Thrombolytic therapy is recommended for NYHA class I/II patients with a small thrombotic burden. METHODS: The results of thrombolytic therapy to treat left-sided PVT (eight mitral, three aortic) with streptokinase (STK) in critically ill NYHA class III/IV patients were analyzed, where surgery was either refused due to financial constraints or by the surgical team. Results were assessed clinically, using fluoroscopy and transthoracic and transesophageal echocardiography. RESULTS: Mechanical bileaflet prosthetic valves (eight mitral, four aortic) were implanted between two and 10 years previously in 11 patients (four females, seven males; age range: 32-54 years). One patient had diabetes and had undergone prior percutaneous coronary intervention with drug-eluting stent implantation to the ostial left main artery. All had cardiomegaly with ejection fraction 24-63% and an increased mean gradient across the immobile prosthetic valve. Patients presented in a hemodynamically unstable state with pulmonary edema and/or hypotensive shock. The International Normalized Ratio was <2.5 in nine patients. Eight patients with mitral valve thrombosis responded to thrombolytic therapy and survived, with complete resolution of thrombus and return of full mobility of leaflets and resolution of valve gradients. To date, all responders have survived (up to five years) without any recurrence of re-thrombosis (PVT). CONCLUSION: Intravenous STK may be life-saving in critically ill NYHA class III/IV patients with left-sided PVT. Thrombolytic therapy is much cheaper and easier to administer than surgical replacement of the thrombosed prosthetic valve.

Spontaneous psoas hematoma in a case of acute myocardial infarction following streptokinase infusion.

INTRODUCTION: Cardiovascular disorders are the major cause of mortality and morbidity globally as well as in India. In India, where resources are limited and majority of patients pay out of their own pocket, thrombolysis is still done for majority of STEMI cases. CASE SCENARIO: A 48-year-old male patient, nonhypertensive and nondiabetic, came to the ER with history of retrosternal chest pain suggestive of angina at rest. An Electrocardiogram (ECG) revealed ST-segment elevation in the anterior leads. Patient was diagnosed with Acute STEMI and thrombolysis was initiated with STK. The following day, the patient complained of pain in his left groin. On examination, there was a swelling and tenderness in left lower abdomen and inability to extend the hip. A CT scan was done, which showed Psoas muscle hematoma. CONCLUSION: Spontaneous bleed into psoas muscle is a very rare complication of thrombolysis that may require surgical exploration.

Subcapsular liver hematoma after fibrinolytic therapy for acute myocardial infarction: a rare case report.

Hemorrhagic complications of thrombolytic therapy are rare but also serious and sometimes life-threatening. Liver hematoma is a very uncommon complication following thrombolytic therapy. We present a rare case of sub-capsular liver hematoma following streptokinase therapy of acute myocardial infarction as a challenging condition. This case report highlights that emergency physicians and cardiologists should be familiar with the significant and uncommon complications of thrombolytic agents, particularly streptokinase which is used generally in under- developed countries.