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1

Kalinin, R. E., E. A. Klimentova, I. A. Suchkov, A. A. Egorov, and A. S. Pshennikov. "The Impact of the Fibrinolytic System on the Outcomes of Thrombolytic Therapy." Russian Sklifosovsky Journal "Emergency Medical Care" 13, no. 4 (2025): 631–40. https://doi.org/10.23934/2223-9022-2024-13-4-631-640.

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Thrombolysis is one of the effectively used methods for treating patients with acute vascular pathology. Despite the high technical success of this therapy, some problems of fibrinolytic treatment still remain unresolved. Resistance to thrombolytic agents with subsequent unsatisfactory reperfusion of the vascular bed is the most important of them. Currently, despite advances in the pharmacotherapy of drugs used in thrombolysis and improvements in the technical basis for its performance, the predictors that influence its outcome are still not clearly defined. The use of fibrinolytic drugs during thrombolysis induces activation of the procoagulative component of hemostasis in the form of increased activity of thrombin, prothrombin fragments 1.2 and the thrombin-antithrombin III complex in response to excessive fibrinolysis caused by this treatment method. This paradoxical procoagulant activation of the hemostatic system may be the cause of the lack of initial reperfusion of the vascular bed in 15–25% of cases, and from 5% to 15% of cases of early thrombotic reocclusion after initially successful thrombolysis. In parallel with the activation of the coagulation link of hemostasis against the background of this type of treatment, changes occur in the functioning of the fibrinolysis system, which directly affects the outcomes of thrombolysis. This paper provides a comprehensive overview of the spectrum of major markers of the fibrinolytic system that have been studied in the context of thrombolysis outcomes in patients with acute vascular pathology. It was concluded that it is necessary to expand the determination of laboratory blood parameters by directly determining the values of plasminogen activator inhibitor-1, thrombin-activated fibrinolysis inhibitor, α2-plasmin inhibitor in order to predict the outcome of thrombolysis.
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2

Bell, William R., and Michael B. Streiff. "Thrombolytic Therapy: A Comprehensive Review of its Use in Clinical Medicine—Part I." Journal of Intensive Care Medicine 8, no. 2 (1993): 56–72. http://dx.doi.org/10.1177/088506669300800202.

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In the first part of this comprehensive review of thrombolytic therapy in clinical medicine, we begin with a brief history of fibrinolysis, followed by a review of the components of die endogenous fibrinolytic system and the currently available plasminogen activators. An in-depth examination of thrombolysis in treatment of acute myocardial infarction follows, Including recommendations for management based on available clinical trial data. New developments in thrombolytic therapy are also discussed.
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3

Fuad, Hayatun, Nur Hidayati, Sri Darmawati, et al. "Prospects of fibrinolytic proteases of bacteria from sea cucumber fermentation products as antithrombotic agent." BIO Web of Conferences 28 (2020): 02006. http://dx.doi.org/10.1051/bioconf/20202802006.

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Cardiovascular disease is among the largest contributors of premature mortality in the world caused by inflammation of blood vessels. The abnormalities provoke thrombus formation or thrombosis blocking blood vessels leading to strokes, heart attacks and coronary artery diseases. Increasing percentage of cardiovascular cases and deaths due to thrombosis has attracted researchers to look for newer thrombolysis agents. Commonly used drugs to treat thrombosis has been limited due to various side effects. Therefore, the search for sources of safer and cheaper fibrinolytic enzymes for handling thrombolysis continues. This study aimed to evaluate potentials of fibrinolytic protease of bacteria isolated from fermented seafood (sea cucumber) products as antithrombotic agents. Information was initially gathered from scientific publications identified using web-based tools including PubMed (National Center for Biotechnology Information), Science Direct (Scopus) and Web of Science (Thomson Reuters) using combinations of search terms including “fibrinolytic enzyme protease”, “endopeptidase”, “fermented food”, “sea cucumber”, “thrombolysis therapy,” “thrombolytic agent,” “fibrinolytic bacteria,” “fibrinolysis,” “protease producing bacteria,” “fibrin degradation,” “holothurians,” etc. We also searched for these terms in national and international organization technical reports and databases. This literature review reveals the prospects of fibrinolytic protease enzymes from bacteria from fermented seafood, particularly sea cucumber as novel antithrombotic agents.
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4

Hvas, Christine Lodberg, and Julie Brogaard Larsen. "The Fibrinolytic System and Its Measurement: History, Current Uses and Future Directions for Diagnosis and Treatment." International Journal of Molecular Sciences 24, no. 18 (2023): 14179. http://dx.doi.org/10.3390/ijms241814179.

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The fibrinolytic system is a key player in keeping the haemostatic balance, and changes in fibrinolytic capacity can lead to both bleeding-related and thrombosis-related disorders. Our knowledge of the fibrinolytic system has expanded immensely during the last 75 years. From the first successful use of thrombolysis in myocardial infarction in the 1960s, thrombolytic therapy is now widely implemented and has reformed treatment in vascular medicine, especially ischemic stroke, while antifibrinolytic agents are used routinely in the prevention and treatment of major bleeding worldwide. Despite this, this research field still holds unanswered questions. Accurate and timely laboratory diagnosis of disturbed fibrinolysis in the clinical setting remains a challenge. Furthermore, despite growing evidence that hypofibrinolysis plays a central role in, e.g., sepsis-related coagulopathy, coronary artery disease, and venous thromboembolism, there is currently no approved treatment of hypofibrinolysis in these settings. The present review provides an overview of the fibrinolytic system and history of its discovery; measurement methods; clinical relevance of the fibrinolytic system in diagnosis and treatment; and points to future directions for research.
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Mishra, Ashish, Jayesh Prajapati, Gajendra Dubey, et al. "Characteristics of ST-elevation myocardial infarction with failed thrombolysis." Asian Cardiovascular and Thoracic Annals 28, no. 5 (2020): 266–72. http://dx.doi.org/10.1177/0218492320932074.

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Background Fibrinolytic therapy is an important reperfusion strategy, especially when primary percutaneous coronary interventions cannot be offered to ST-elevation myocardial infarction patients. Given that failed reperfusion after fibrinolytic therapy is common, it is pragmatic that the predictors, outcomes, and angiographic profiles of patients with failed thrombolysis are carefully scrutinized. Methods We prospectively studied clinical variables and outcomes over 30 months in 243 ST-elevation myocardial infarction patients who received fibrinolytics as primary treatment. Logistic regression analysis was used to identify predictors of failed thrombolysis. Results Failed thrombolysis occurred in 38.68% of patients with a mean window period of 6.58 ± 1.42 h, and 55.32% of patients with failed thrombolysis had Killip class >I on presentation. Risk factors such as diabetes mellitus (55.32%), dyslipidemia (60.64%) and obesity (77.66%) were frequently associated with failed thrombolysis; 73.40% of patients with failed thrombolysis had Thrombolysis in Myocardial Infarction flow grade 0/1 in the infarct-related artery, and 58.51% of such patients needed a rescue percutaneous coronary intervention. The mean Thrombolysis in Myocardial Infarction risk score was 5.46 ± 2.77 in failed thrombolysis patients, with mortality of 4.25% at the 6-month follow-up. Conclusion Non-resolution of presenting symptoms and ST changes on electrocardiography at 90 min served as the earliest indicators of failed thrombolysis, with a significant angiographic correlation. Clinical variables such as delayed presentation (>6 h), dyspnea, Killip class >I, cardiogenic shock, Thrombolysis in Myocardial Infarction score, and conventional risk factors including diabetes mellitus, dyslipidemia, and obesity represented cluster of predictors of failed thrombolysis.
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6

Chopard, Romain, Fiona Ecarnot, and Nicolas Meneveau. "Catheter-directed therapy for acute pulmonary embolism: navigating gaps in the evidence." European Heart Journal Supplements 21, Supplement_I (2019): I23—I30. http://dx.doi.org/10.1093/eurheartj/suz224.

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Abstract Systemic thrombolysis for acute pulmonary embolism (PE) reduces the risk of death and cardiovascular collapse but is associated with an increased rate of bleeding. The desire to minimize the risk of bleeding events has driven the development of catheter-based strategies for pulmonary reperfusion in PE. These catheter-based strategies utilize lower-dose fibrinolytic regimens or purely mechanical techniques to expedite removal of the embolus. Several devices providing mechanical or suction embolectomy and catheter-directed thrombolysis, with or without facilitation by ultrasound, have been tested. Data are inconsistent regarding the efficacy and safety of mechanical and suction embolectomy. The most comprehensive data on catheter-based techniques stem from trials of ultrasound-facilitated catheter fibrinolysis. Ultrasound-facilitated catheter fibrinolysis relieves right ventricular pressure overload with a lower risk of major bleeding and intracranial haemorrhage than historical rates with systemic fibrinolysis. However, further research is required to determine the optimal application of ultrasound-facilitated catheter fibrinolysis and other catheter-based therapies in patients with acute PE.
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7

Stringer, Kathleen A. "Beyond Thrombolysis: Other Effects of Thrombolytic Drugs." Annals of Pharmacotherapy 28, no. 6 (1994): 752–56. http://dx.doi.org/10.1177/106002809402800613.

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OBJECTIVE: To review the effects of plasminogen activators (tissue plasminogen activator, streptokinase, and anistreplase) on fibrinogen and thrombin, platelets, complement, blood rheology, and neutrophils. DATA SOURCES: A MEDLINE search, as well as a review of recent scientific abstracts, was conducted to identify pertinent literature. STUDY SELECTION: Focus was placed on studies conducted in humans. However, many in vitro studies have been performed to fully elucidate the effect of plasminogen activators on different aspects of hemostasis and on the fibrinolytic and immune systems. DATA EXTRACTION: Data from in vitro, human, and animal studies were evaluated. DATA SYNTHESIS: There is a discrepancy between 9O-minute patency and mortality in acute myocardial infarction patients treated with thrombolytic drugs. This could be caused, in part, by other hematologic and immunologic effects of thrombolytic drugs. Though the emphasis of clinical trials has been infarct-related artery patency, left ventricular function, and mortality, some studies have evaluated the effect of thrombolytic agents on fibrinogen and thrombin, platelets, blood rheology, complement, and neutrophils. This review discusses the alteration of systemic hematologic and immunologic parameters by thrombolytic drugs and the possible clinical implications of these effects. CONCLUSIONS: Although the interactions between thrombolytic drugs, hemostasis, and the fibrinolytic and immune systems are complex and still not fully understood, it appears that these drugs differ in their effects on these systems. A greater understanding of these properties and their clinical implications may ultimately enhance the care and outcome of acute myocardial infarction patients treated with thrombolytic therapy.
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8

Gensini, Gian Franco, Marco Comeglio, and Andrea Colella. "Coronary and Peripheral Thrombolysis: Current Status and Recommendations." Clinical and Applied Thrombosis/Hemostasis 4, no. 2 (1998): 82–86. http://dx.doi.org/10.1177/107602969800400202.

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Thrombolytics are mainly indicated in acute myo cardial infarction (AMI), with limited evidence of usefulness in stroke and acute peripheral arterial occlusion (PAO). Throm bolytics can successfully dissolve thrombi in any vessel, but clinical benefit varies according to the involved vascular bed. The anticipated clinical benefit of thrombolytics in treating AMI, stroke, and PAO must be carefully balanced against the risk of bleeding (especially intracranial hemorrhage). In AMI, fibrinolytic agents reduce mortality rates by as much as 30% when started within 6 h of symptom onset and by as much as 50% if given within 1 to 2 h. Therefore, the timing of fibrino lytic therapy largely determines the magnitude of reduction in mortality after AMI. Streptokinase is a well-documented treat ment for AMI, with r-TPA plus IV heparin enabling better results, specially in anterior MI and in the elderly. Reteplase was not superior to alteplase in GUSTO-III and TNK-TPA is in the early phase of investigation. However their ease of admin istration and potential for more potent and specific clot lysis may prove advantageous. In acute stroke, the most recently reported phase III trials of streptokinase and recombinant tissue plasminogen activator (r-TPA) have stressed the importance of the clinical benefit/hemorrhage risk balance. These studies sup ported the viewpoint that the use of fibrinolytic agents for stroke must be limited to r-TPA in well-characterized patients and with a narrow time window. Finally, local administration of thrombolytic agents in acute arterial thrombosis, mainly in the limbs, is commonly used by interventional radiologists. Goods results have been reported in terms of safety and effec tiveness in the treatment of acute lower extremity ischemia. The preliminary results of the Thrombolysis or Peripheral Ar terial Surgery (TOPAS) trial suggest that recombinant uroki nase therapy (4,000 IU/min) is associated with limb salvage and patient survival rates similar to those achieved with sur gery, concurrent with a reduced need for complex surgery after thrombolytic intervention. In summary, AMI represents the most important indication for thrombolysis, with large amounts of data supporting its use. In acute stroke, there is less evidence of efficacy and it is limited to a few well-characterized patients, whereas local ad ministration in patients with acute PAO may favorably affect patient outcome despite of the absence of evidence of improved limb salvage. Key Words: Thrombolysis—Myocardial infarc tion—Stroke—Acute peripheral arterial occlusion.
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9

Shibuya, Akira, Haruhiko Ninomiya, Masaki Nakazawa, Toshiro Nagasawa, Yasuhiro Yoda, and Tsukasa Abe. "Oxymetholone Therapy in Patients with Familial Antithrombin III Deficiency." Thrombosis and Haemostasis 60, no. 03 (1988): 495–97. http://dx.doi.org/10.1055/s-0038-1646998.

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SummaryThree patients with familial antithrombin III (ATIII) deficiency, who also have histories of thromboembolism, were treated with oxymetholone in combination with warfarin. Thrombolysis was observed in one patient with acute thrombosis of inferior vena cava during the oxymetholone and warfarin therapy. No further thromboembolic episodes occurred in these patients after initiation of warfarin with or without oxymetholone. The levels of plasma ATIII, α1-antitrypsin, plasminogen and Cl-inactivator were significantly increased in all patients after the introduction of oxymetholone therapy. This suggests that oxymetholone augments anticoagulant and fibrinolytic activity. Hence we consider that oxymetholone in combination with warfarin may be possible thrombolytic therapy in patients with familial ATIII deficiency.
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10

Mulla, A., and K. de Wit. "P106: Systemic thrombolysis for suspected high-risk pulmonary embolism: a retrospective medical record review." CJEM 20, S1 (2018): S94. http://dx.doi.org/10.1017/cem.2018.304.

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Introduction: Current treatment guidelines advocate for the aggressive management of both high-risk and subsets of moderate-risk pulmonary embolism (PE) with fibrinolytic therapy. However, there is limited evidence on the risks and benefits of fibrinolytic therapy in PE, with mortality improvement still to be proven. This study aimed to report the incidence of major bleeding and death after thrombolysis for PE. Methods: A health records review was performed on data from two hospitals between 2007 and 2017. Pharmacy identified all patients who had received either alteplase or tenecteplase. Trained abstractors reviewed each chart to determine the indication for thrombolytic therapy. Patients were included if they received systemic thrombolysis for diagnosed or presumed PE. Data was extracted on 30-day mortality, International Society of Thrombosis and Hemostasis defined major bleeding within 30 days, premorbid anticoagulant and antiplatelet prescription, age, sex, comorbidities, renal function, history of bleeding, type and dose of thrombolytic and category of PE (high or moderate risk). Results: 1534 patients were identified, of which 72 received systemic thrombolysis for PE. The median age was 57, 34 were male, 17 with a history of venous thrombosis and 12 with cancer. Fifty-four were classified as having high-risk PE, of whom 39 received cardiopulmonary resuscitation (CPR) when thrombolysis was administered. Formal confirmatory imagining for PE was obtained in only 23/39 patients who were in cardiac arrest. Eighteen patients were classified as moderate-risk PE. The incidence of major bleeding was 28/54 (52%, 95% CI 39-65%), and 3/18 (17%, 95% CI 6-39%) for the high and moderate risk groups respectively. There were 4 intracranial bleeds, all in the high-risk PE group. The only significant predictor of major bleeding was the need for CPR at the point of administration of the thrombolytic agent (OR 2.6, 95% CI 1.0-7.5, adjusted for age). Thirty-four patients died within 30 days (47%, 95% CI 36-59%), all in the high-risk PE group. Death was not associated with any demographic variable on univariate analysis. Death occurred in 28/39 (72%, 95%CI 56-83%) patients who received CPR and 6/33 (18%, 95% CI 9-34%) who did not. Conclusion: We found a high incidence of 30-day major bleeding and death following administration of thrombolysis for PE which will help inform future prognostic discussions in our institution.
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Wever, M. L. G., K. D. Liem, W. B. Geven, and R. B. Tanke. "Urokinase Therapy in Neonates with Catheter Related Central Venous Thrombosis." Thrombosis and Haemostasis 73, no. 02 (1995): 180–85. http://dx.doi.org/10.1055/s-0038-1653748.

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SummaryThe results of fibrinolytic therapy with urokinase were evaluated in 26 neonates with catheter related central venous thrombosis. Complete thrombolysis could be achieved in 13 patients (50%), partial thrombolysis in 3 patients (12%). No effect was seen in 10 patients (38%). Therapy success was influenced by age, size and location of the thrombus. Coincidence of infection occurred in 16 patients (62%). Mild hemorrhagic complications were seen in 2 patients (8%), no other significant side effects were observed. Nine patients with residual thrombosis were treated with oral anticoagulants following urokinase resulting in resolution of the thrombus in 6 patients within 3 months (67%). The incidence of asymptomatic recurrent thrombosis was high (28%). Urokinase might be an effective and safe treatment for central venous thrombosis in neonates. Prophylactic antibiotic therapy during the infusion of urokinase and long-term treatment with oral anticoagulants after thrombosis are advisable. Early detection of thrombosis might enhance the success rate of fibrinolytic therapy. Therefore, we strongly recommend routine echocardiographic screening of central venous catheters.
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12

Buryachkovskaya, L. I., N. V. Lomakin, E. A. Shirokov, N. K. Vitko, and D. N. Verbovoy. "A Case of Successful Thrombolysis on the Verge of a Reperfusion Revolution in Coronary Cardiology and Vascular Neurology." Kardiologiia 59, no. 6 (2019): 91–96. http://dx.doi.org/10.18087/cardio.2019.6.n686.

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Thrombolytic therapy (TLT), as a method of treatment, began to develop in the second half of the 50s of the last century. At that time, there was an accumulation of data on its effectiveness, side effects and contraindications, as well as the development of fibrinolytic drugs, such as fibrinolysin, streptokinase, urokinase, and the conditions for their administration. Official recognition of TLT in regulatory documents began only in the 80s after the development of more effective and safe tissue plasminogen activators. However, on the threshold of an era of development in this area in the treatment of patients with thrombosis of the coronary, carotid, and other peripheral vascular regions, the researchers obtained conflicting data on the results of the use of thrombolytics. There was no concept of a therapeutic window for the use of TLT, there was no data on possible combinations of thrombolytic drugs with anticoagulants, the high probability of bleeding prevented widespread introduction of the method into clinical practice. At that time, vascular imaging and laboratory diagnostics were not sufficiently developed, there was no consensus of the world’s leading experts on the benefits of thrombolysis. The use of TLT in acute arterial thrombosis required not only clinical experience, but also courage and ability to make non-standard decisions. The authors of the article analyze in detail the case of rescuing a patient with progressive thrombotic occlusion of the arteries of the brain stem. Then the pioneer in the field of thrombolytic therapy E. I. Chazov and his colleagues took responsibility for the application in this situation of an insufficiently studied treatment method with uncertain consequences. This decision was not due to the identity of the patient or the threat of an internal investigation. Marshal or soldier – it did not matter for E. I. Chazov and his colleagues. If doctors in this clinical situation relied on recommendations, orders and standards, then such a patient would have to wait thrombolysis for another 30 years.
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Khan, Md Monir Hossain, Md Afzalur Rahman, Abdullah Al Shafi Majumder, et al. "Prediction of Reperfusion and Infarct-Related Artery Patency after Thrombolysis in Acute Anterior Myocardial Infarction by Degree of P Wave Dispersion on ECG." Bangladesh Heart Journal 32, no. 2 (2018): 100–105. http://dx.doi.org/10.3329/bhj.v32i2.36096.

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Background: The prognosis of patients with persistent occlusion of the infarct related artery (IRA), despite lytic therapy is poor. Early detection of successful reperfusion and IRA patency is of great importance in terms of prognosis and identification of candidates for rescue percutaneous coronary intervention (PCI). P wave dispersion (PWD), a new parameter measured before and after fibrinolytic therapy (FT) is supposed to predict successful reperfusion in patients with anterior acute myocardial infarction (AMI).Objectives:To examine the prediction of successful reperfusion and infarct related artery (IRA) patency by measuring P wave dispersion in 12-lead surface ECG.Method:132 patients were selected and divided into two groups on the basis of ST segment resolution (STR) after 120 minutes of thrombolysis. Group I: patients with STR >70%; Group II: patients with STR < 70%. All patients underwent coronary angiography (CAG). IRA patency was considered if TIMI flow grade was >2.Results: Mean age of the successfully thrombolysed group was 49.12±9.54 and mean age of failedthrombolysis group was 52.08±8.23 years. Though higher age was associated with failed thrombolysis and it was statistically insignificant (p=0.06). Patients with higher BMI showed no significant difference in thrombolysis. It was observed that diabetes mellitus and dyslipidemia were significantly higher in group II patients (p=0.04 and p=0.03, respectively). The mean level of PWD after 120 minutes of thrombolysis (PWD120) was statistically significant (p=0.001) between two groups. After multivariate regression analysis PWD120 was found to be the significant predictor of ST segment resolution as well as IRA patency (OR = 1.101; 95% CI = 1.012 – 1.240; p = 0.01).Conclusion: P wave dispersion (PWD) in patients receiving thrombolytic therapy can be a predictor of successful reperfusion and patent infarct related artery (IRA). PWD values, in combination with other reperfusion parameters, can contribute to the identification of rescue PCI candidates.Bangladesh Heart Journal 2017; 32(2) : 100-105
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14

Gantsgorn, E. V., A. V. Safronenko, M. L. Maksimov, A. A. Baloyan, I. M. Malleev, and R. M. Manvelyan. "Possibilities of thrombolytic therapy of acute myocardial infarction with ST." Farmacevticheskoe delo i tehnologija lekarstv (Pharmacy and Pharmaceutical Technology), no. 4 (September 6, 2024): 47–55. http://dx.doi.org/10.33920/med-13-2404-05.

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For a long time, the global medical community has been discussing the issue of the strategic role of thrombolytic pharmacotherapy and percutaneous coronary intervention in the treatment of acute ST-elevation myocardial infarction (STEMI). Today, based on the results of large studies, the European Society of Cardiology recommends preferring invasive tactics to thrombolysis in case of infarction complication by cardiogenic shock or severe heart failure, regardless of the duration of the delay associated with the organization of endovascular intervention. Meanwhile, STEMI remains a frequent and lifethreatening condition requiring immediate reperfusion, and therefore, the sequential use of both tactics, as well as thrombolytic therapy alone, is actively being discussed, especially in areas where there is no hospital with the technical capability to perform endovascular dilation of the affected vascular segment. In this regard, the thrombus may remain the only pathogenetic link for action to restore myocardial blood supply. Recent studies of specific fibrinolytic agents have demonstrated good prospects and safety of alteplase and tenecteplase, in particular. Thus, given the already proven effectiveness of thrombolysis, as well as its speed of action and ease of implementation, in our opinion, further in-depth study and modification of approaches to the use of this group of drugs in clinical practice is necessary.
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Kumar, Amit, Shweta Tanwar, and Rajesh Chetiwal. "N-terminal pro-B-type natriuretic peptide as a predictive marker of the outcomes of fibrinolytic therapy in acute ST-elevation myocardial infarction." MGM Journal of Medical Sciences 11, no. 2 (2024): 217–22. http://dx.doi.org/10.4103/mgmj.mgmj_32_24.

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Abstract Background: Risk assessment is vital in delivering appropriate treatment and enhancing patient outcomes during acute ST-elevation myocardial infarction (STEMI). This study sought to ascertain the significance of NT-proBNP in predicting the outcome of thrombolysis in acute STEMI. Materials and Methods: In this prospective study, we enrolled individuals with acute STEMI who underwent fibrinolytic therapy. Plasma N-terminal-proBNP (NT-proBNP) levels were assessed upon admission. Patients were categorized as thrombolysis success or failure groups based on electrocardiogram (ECG) criteria. The outcomes were measured in terms of in-hospital mortality and adverse cardiovascular events. Results: Thrombolysis achieved success in 59.13% of acute STEMI cases. Patients experiencing failed thrombolysis had a significantly longer mean time to reperfusion than those with successful thrombolysis (4.74 ± 2.42 vs. 5.97 ± 2.35 h, P = 0.0078). The median baseline NT-proBNP concentration was 983 pg/mL (interquartile range 777–2987 pg/mL). The plasma NT-proBNP levels on admission were notably higher in the thrombolysis failure group (P < 0.001). NT-proBNP, time to reperfusion, heart rate, blood urea, and serum uric acid exhibited negative correlations with thrombolysis outcomes. The most prevalent adverse event was cardiac failure. Receiver operating characteristic (ROC) curve analysis indicated a robust association between NT-proBNP and in-hospital mortality. High NT-proBNP (>983 pg/mL) and prolonged time to reperfusion (>6 h) emerged as independent predictors of thrombolysis failure on multivariate logistic regression analysis (P = 0.017 and 0.035, respectively). Conclusion: Elevated plasma NT-proBNP upon admission during acute STEMI serves as a robust predictor for both fibrinolytic therapy failure and in-hospital mortality.
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Wagner, Andreas, Marianne Gwechenberger, Harald Herkner, et al. "Attenuation of Thrombolysis-induced Increase of Plasminogen Activator Inhibitor-1 by Intravenous Enalaprilat." Thrombosis and Haemostasis 79, no. 01 (1998): 140–43. http://dx.doi.org/10.1055/s-0037-1614233.

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SummaryWe examined the effect of intravenous enalaprilat on the course of PAI-1 plasma levels in 23 patients with acute myocardial infarction undergoing thrombolytic therapy. All patients received 100 mg aspirin, 1000 IU/h heparin, thrombolysis with 100 mg rt-PA within 90 min, and betablockers. Eleven out of 23 patients received 5 mg enalaprilat intravenously prior to thrombolysis. Blood samples for determination of PAI-1 plasma levels were collected on admission, 2, 4, 6, 12, and 24 h after thrombolysis. PAI-1 plasma levels in patients receiving enalaprilat were similar to those of the control patients before thrombolysis (5 ng/ml, 95% confidence interval: 2-10 vs. 7 ng/ml, 95% confidence interval: 2-10; p = 0.5). The PAI-1AUC was 9 ng/ml/h (95% confidence interval: 5-10) in the enalaprilat group and 19 ng/ml/h (95% confidence interval: 13-26) in the control group (p = 0.0006). The maximum difference was observed 6 h after thrombolysis (enalaprilat: 13 ng/ml, 95% confidence interval: 5-25, control: 42 ng/ml, 95% confidence interval: 18-55; p = 0.003).Our study clearly demonstrates that application of intravenous enalaprilat prior to thrombolysis attenuates the thrombolysis-related increase of PAI-1. This finding may suggest a possible therapeutic approach to influence the fibrinolytic system in patients with acute myocardial infarction after thrombolysis.
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Stewart, Ronald, James Fredenburgh, and Jeffrey Weitz. "Mechanism of Action of Plasminogen Activators." Thrombosis and Haemostasis 82, no. 08 (1999): 974–82. http://dx.doi.org/10.1055/s-0037-1615941.

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IntroductionAcute coronary ischemic syndromes and stroke are usually caused by thrombosis in arteries where obstruction leads to ischemia of the heart or brain, respectively. Likewise, venous thrombosis predisposes to pulmonary emboli that cause infarction of lung tissue by blocking pulmonary arteries. Although antithrombotic drugs form the cornerstone of treatment of established thrombosis, pharmacologic lysis of fibrin thrombi, using plasminogen activators, is a widely used approach for treatment of acute myocardial infarction and selected cases of stroke or venous thromboembolism.Plasminogen activators cause thrombus dissolution by initiating fibrinolysis (Fig. 1). The fibrinolytic system is comprised of inactive plasminogen, which is converted to plasmin by plasminogen activators.1 Plasmin, a trypsin-like serine protease, degrades fibrin into soluble fibrin degradation products. The fibrinolytic system is regulated to provide efficient localized activation of plasminogen on the fibrin surface, yet prevent systemic plasminogen activation. To localize plasminogen activation to the fibrin surface, both plasminogen and tissue-type plasminogen activator (t-PA), the major initiator of intravascular fibrinolysis, bind to fibrin. Plasminogen activator inhibitors,2 the most important of which is type-1 plasminogen activator inhibitor (PAI-1), prevent excessive plasminogen activation by t-PA and urokinase-type plasminogen activator (u-PA). Systemic plasmin is rapidly inhibited by α2-antiplasmin, whereas plasmin generated on the fibrin surface is relatively protected from inactivation by α2-antiplasmin.3 The beneficial effect of thrombolytic therapy reflects dissolution of fibrin within occlusive thrombi and subsequent restoration of antegrade blood flow. Bleeding, the major side effect of thrombolytic therapy, occurs because plasmin is a relatively nonspecific enzyme that does not distinguish between fibrin in occlusive thrombi and fibrin in hemostatic plugs. In addition, circulating plasmin also degrades fibrinogen and other clotting factors, a phenomenon known as the systemic lytic state. Although the contribution of the systemic lytic state to bleeding remains controversial, much attention has focussed on the development of plasminogen activators that produce thrombolysis without depleting circulating fibrinogen in the hope that agents with greater fibrin-specificity will produce less bleeding.In addition to causing bleeding, currently available plasminogen activators have other limitations. Despite aggressive dosing regimens and adjunctive antithrombotic drugs, up to 25% of coronary thrombi are resistant to thrombolysis at 60 to 90 minutes. Early thrombotic reocclusion of previously opened coronary arteries further reduces the benefits of thrombolytic therapy.4-6 These problems have triggered the quest for more potent thrombolytic agents that have the potential to overcome factors that render some thrombi resistant to lysis. Furthermore, to simplify administration, plasminogen activators with longer half-lives have been developed so that bolus dosing is possible.This chapter reviews the mechanism of action of currently available plasminogen activators, including agents with greater fibrin-specificity, longer half-lives, and a potential for increased thrombolytic potency.
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18

Szuchy Kristiansen, Eva, Hannah Holm Vestergaard, Boris Modrau, and Lorenz Martin Oppel. "Acute Ischemic Stroke in Late Pregnancy Treated with Intravenous Thrombolysis and Endovascular Therapy." Case Reports in Neurology 11, no. 1 (2019): 41–46. http://dx.doi.org/10.1159/000496084.

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Pregnancy has usually been an exclusion criterion in clinical trials with thrombolysis and endovascular therapy in acute ischemic stroke. For that reason, these therapies are not recommended causing lack of evidence and vice versa. In this case report, we describe a pregnant woman in week 33 + 3 presenting with acute ischemic stroke, which was successfully treated with systemic thrombolysis and endovascular therapy, resulting in a good clinical outcome for both mother and child. The altered fibrinolytic system and the risk factors related to pregnancy constitute a challenge for clinicians when choosing the most suitable treatment modality for treating acute ischemic stroke in pregnancy. It is still uncertain whether thrombolysis in combination with endovascular therapy or endovascular therapy alone is the most appropriate treatment option. However, there is slowly growing evidence that thrombolysis and thrombectomy in pregnancy are feasible and safe with a good clinical outcome for both the mother and the child.
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19

Dimitrova, E., I. Bayraktarova, D. Kyuchukov, V. Kostova, and E. Trendafilova. "Systemic thrombolysis for mechanical prosthetic valve thrombosis - case report and review of literature." Bulgarian Cardiology 29, no. (4) (2023): 111–24. https://doi.org/10.3897/bgcardio.29.e113537.

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Prosthetic valve thrombosis is one of the life-threatening complications in patients with prosthetic heart valves. It is more common in mechanical prosthetic valves in the setting of inadequate or missing anticoagulation. Besides optimization of anticoagulation urgent surgery or thrombolytic therapy should be considered but both are associated with an increased risk for complications and mortality. We report a case of a patient with imaging data for mechanical prosthetic mitral valve thrombosis. Considering the individual patient's characteristics and the published guidelines we decided to perform systemic thrombolysis with ultra-slow low-dose infusion of tissue-type plasminogen activator. The therapy was successful without any bleeding or thromboembolic complications.
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20

Ring, Michael E., Samuel M. Butman, Denise C. Bruck, William M. Feinberg, and James J. Corrigan. "Fibrin Metabolism in Patients with Acute Myocardial Infarction During and After Treatment with Tissue-Type Plasminogen Activator." Thrombosis and Haemostasis 60, no. 03 (1988): 428–33. http://dx.doi.org/10.1055/s-0038-1646984.

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SummaryIn order to define some of the determinants of successful thrombolysis and reocclusion during fibrinolytic therapy for acute myocardial infarction (AMI), specific molecular markers of fibrin metabolism were serially measured in 15 patients with AMI treated with tissue-type plasminogen activator (t-PA). Fibrin formation was assessed by measurement of fibrinopeptide A (FpA) and fibrinolysis by assay of B-P peptides 1—42 and 15—42 and crosslinked fibrin degradation products (XDP). At baseline, FpA levels were high while markers of fibrinolysis were near normal. Following a 90-minute infusion of t-PA (0.5—1.1 mg kg−1 hr−1), all markers of fibrinolysis increased. Levels of FpA remained elevated despite heparin at the initiation of cardiac catheterization. None of these markers discriminated between patients with successful reperfusion from those without. At 4 hours, B-β 15—42 peptide and XDP levels remained elevated suggesting persistence of fibrinolysis beyond the short circulatory half-life of t-PA. FpA levels at 4 hours were lower in patients who underwent acute coronary angioplasty compared to those who received additional low dose t-PA (12.3 ± 4.5 vs. 30.4 ± 5.5 ng/ ml, p <0.05). By 48 hours, markers of fibrinolysis had returned toward normal except in 2 patients with persistently elevated B-P 15—42 peptide levels who suffered reocclusion on days 5 and 6 (75 and 44 vs. 29 ± 3 nM, p <0.005). In conclusion, molecular markers of fibrin metabolism during fibrinolytic therapy may provide clinically relevant data.
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21

Zou, Junjie, Yuanyong Jiao, Jun Jiang, et al. "Quantitation of Venous Clot Lysis With D-Dimer Assay During Catheter-Directed Thrombolysis for Lower Extremity Deep Venous Thrombosis." International Surgery 101, no. 9-10 (2016): 487–91. http://dx.doi.org/10.9738/intsurg-d-15-00088.1.

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This study evaluated whether D-dimer (DD) concentration analysis is a useful approach for noninvasive monitoring of clot lysis during catheter-directed thrombolysis (CDT) for deep vein thrombosis (DVT). DD levels have been found to be elevated during fibrinolytic therapy for DVT. Therefore, measuring the level of DD is a potential alternative method to assess the effect of fibrinolytic therapy. From January 2013 to March 2014, 32 patients with symptomatic acute DVT involving the iliac or femoral veins were treated using CDT. Urokinase was the thrombolytic agent. Demographics, procedural details, DD concentration, and thrombus score were recorded before and after the thrombolytic therapy. The peak DD concentration was 35.35 ± 11.18 μg/mL during CDT therapy, and the time-integrated DD concentration was 157.95 ± 69.46 μg·d/mL. The peak DD concentrations were higher in patients with substantial lysis compared with those in patients with minimal or no lysis (40 ± 0 versus 30.7 ± 14.57 μg/mL; P = 0.016). The time-integrated DD concentrations were also higher in patients with substantial lysis compared with those in patients with minimal or no lysis (194.14 ± 37.57 units versus 121.75 ± 75.93 units, P = 0.002). There was a moderate correlation (r = 0.57) between the peak DD level and the lysed clot volume. There was also a correlation between the time-integrated DD and clot lysis (r = 0.65). DD concentration analysis offers an alternative approach to noninvasive monitoring of venous clot lysis during CDT for DVT.
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22

Ibrahim, Tunde Maiyaki. "The Use of Intravenous Tenecteplase in Acute Ischemic Stroke after Idarucizumab Reversal of Dabigatran Anticoagulant Effects; Experience from a Regional Hospital Directed by Video Telemedicine Stroke Specialist." Clinical Studies and Medical Case Reports 9, no. 2 (2022): 1–4. http://dx.doi.org/10.24966/csmc-8801/1000140.

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Novel Oral Anticoagulants (NOACs) are widely used in patients with non-valvular atrial fibrillation to prevent Acute Ischemic Stroke (AIS) and other thrombo- embolic phenomena. The management of AIS with Intravenous Thrombolysis Therapy (IVT), also known as fibrinolytic therapy in people who are taking NOACs poses a great challenge due to increased risks of hemorrhage and intracranial bleeding. We present the case of a 77-year-old man on dabigatran for atrial fibrillation who woke up with an extensive right middle cerebral artery ischemic stroke and had his anticoagulant effects reversed with idarucizumab before successful thrombolysis with intravenous tenectaplase.
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23

Pislaru, Sorin V., and Frans Van de Werf. "TNK-tPA for Acute Myocardial Infarction: The Clinical Experience." Thrombosis and Haemostasis 82, S 01 (1999): 117–20. http://dx.doi.org/10.1055/s-0037-1615567.

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SummaryThrombolytic therapy has become the mainstay of treatment for acute transmural myocardial infarction. Present fibrinolytic regimens have a number of shortcomings, including the failure to induce early and sustained reperfusion in as many as 40-50% of the patients, and to prevent reocclusion in another 10-20% of the patients. The efforts for improving thrombolysis are focused on the development of new agents (fibrinolytics, anticoagulants, and antiplatelet agents). TNK-tPA is a triple combination mutant of wild-type tissue plasminogen activator that exhibits a longer plasma half-life, an enhanced fibrin-specificity, and an increased resistance to the plasminogen activator inhibitor-1. This paper summarizes the results of clinical trials with TNK-tPA in acute myocardial infarction.
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24

Perkins, W. R., D. E. Vaughan, S. R. Plavin, et al. "Streptokinase Entrapment in Interdigitation-Fusion Liposomes Improves Thrombolysis in an Experimental Rabbit Model." Thrombosis and Haemostasis 77, no. 06 (1997): 1174–78. http://dx.doi.org/10.1055/s-0038-1656133.

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SummaryThe successful design of new thrombolytic agents depends on providing these agents with increased clot selectivity. As recently demonstrated (10), entrapment of tissue plasminogen activator into liposomes apparently provided the selective targeting needed to improve the efficacy of this fibrinolytic agent. To test whether liposomal entrapment would benefit streptokinase, a fibrinolytic agent with a different mode of action and inactivation, we compared liposomal streptokinase with free streptokinase in an experimental rabbit model of thrombolysis.First we adapted a new method to produce liposomes of high entrapment efficiency, termed interdigitation-fusion (IF) liposomes, for the encapsulation of streptokinase. This system was then tested in an in vivo rabbit model of thrombolysis where animals with established clots were infused with either free streptokinase (40,000 U/kg), liposomally entrapped streptokinase, free streptokinase + empty liposomes, or the corresponding amount of empty liposomes or saline. Significant differences (p <0.05) in the percent clot lysis were observed between saline control (22.4 ± 3.3%; mean ± S.E.), free streptokinase (36.3 ± 3.4%), and liposomal streptokinase (47.4 ± 1.4%). Importantly, animals treated with empty liposomes experienced a level of thrombolysis (32.4 ± 2.8%) not different to that produced by free streptokinase or empty liposomes plus free streptokinase (38.0 ± 2.0%). We believe the effect of liposomes alone is due to a transient redistribution or margination of circulating platelets.When tested in rabbits immunized against streptokinase, liposomal (33.8 ± 1.5%) but not free streptokinase (29.3 ± 2.1%) showed significant thrombolytic activity compared to saline (22.4 ± 3.3%) (p <0.05). The thrombolytic activity was comparable to free streptokinase in nonimmunized rabbits. This suggests liposomal streptokinase would have better thrombolytic activity than streptokinase alone and still provide to those patients possessing high levels of anti-streptokinase antibodies (5% of the population) the equivalent degree of therapy expected from free streptokinase.
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25

Hong, Ting-Ting, Jinbao Huang, and Benedict R. Lucchesi. "Effect of thrombolysis on myocardial injury: recombinant tissue plasminogen activator vs. alfimeprase." American Journal of Physiology-Heart and Circulatory Physiology 290, no. 3 (2006): H959—H967. http://dx.doi.org/10.1152/ajpheart.00649.2005.

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Plasmin-dependent thrombolytic agents are potentially prothrombotic and proinflammatory. Alfimeprase, a zinc-containing metalloproteinase, degrades fibrin directly and achieves thrombolysis independent of plasmin formation. This study examines the hypothesis that thrombolysis in the absence of plasmin generation results in improved myocardial salvage on reperfusion. The thrombolytic effects of recombinant tissue plasminogen activator [rt-PA; 0.022 mg/kg, 1/10 of which was administered as a loading dose; the rest (9/10) was infused over 60 min by intracoronary (ic) administration] or alfimeprase (0.5 mg/kg over 1 min ic) were evaluated in a canine model of arterial thrombosis involving electrolytic injury of the left circumflex (LCX) coronary artery. Both agents induced thrombolysis, with onset of reperfusion being more rapid after alfimeprase compared with rt-PA (1.5 ± 0.6 vs. 10.1 ± 2.1 min). In the absence of adjunctive therapy, time to reocclusion after alfimeprase was 3.2 ± 0.5 min compared with 77.5 ± 31.9 min with rt-PA. The glycoprotein IIb/IIIa platelet receptor antagonist CRL-42796 prolonged reperfusion time after thrombolysis with alfimeprase or rt-PA. The effect of each lytic agent on myocardial infarct size was examined in a separate group of dogs subjected to 60 min of LCX coronary artery ligation and 4 h of reperfusion. Myocardial infarct size, expressed as percentage of the risk region, was larger (32.16 ± 3.95%) after rt-PA compared with alfimeprase (19.85 ± 3.61%) or that of the saline control group (18.46 ± 3.34%). rt-PA in contrast to alfimeprase, a direct-acting fibrinolytic agent, is associated with an increase in myocyte reperfusion injury.
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26

Price, Laura C., Benjamin Garfield, Caroline Bleakley, et al. "Rescue therapy with thrombolysis in patients with severe COVID-19-associated acute respiratory distress syndrome." Pulmonary Circulation 10, no. 4 (2020): 204589402097390. http://dx.doi.org/10.1177/2045894020973906.

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Acute respiratory distress syndrome in patients with Coronavirus disease 19 is associated with an unusually high incidence of pulmonary embolism and microthrombotic disease, with evidence for reduced fibrinolysis. We describe seven patients requiring invasive ventilation for COVID-19-associated acute respiratory distress syndrome with pulmonary thromboembolic disease, pulmonary hypertension ± severe right ventricular dysfunction on echocardiography, who were treated with alteplase as fibrinolytic therapy. All patients were non-smokers, six (86%) were male and median age was 56.7 (50–64) years. They had failed approaches including therapeutic anticoagulation, prone ventilation ( n = 4), inhaled nitric oxide ( n = 5) and nebulised epoprostenol ( n = 2). The median duration of mechanical ventilation prior to thrombolysis was seven (5–11) days. Systemic alteplase was administered to six patients (50 mg or 90 mg bolus over 120 min) at 16 (10–22) days after symptom onset. All received therapeutic heparin pre- and post-thrombolysis, without intracranial haemorrhage or other major bleeding. Alteplase improved PaO2/FiO2 ratio (from 97.0 (86.3–118.6) to 135.6 (100.7–171.4), p = 0.03) and ventilatory ratio (from 2.76 (2.09–3.49) to 2.36 (1.82–3.05), p = 0.011) at 24 h. Echocardiographic parameters at two (1–3) days ( n = 6) showed right ventricular systolic pressure (RVSP) was 63 (50.3–75) then 57 (49–66) mmHg post-thrombolysis ( p = 0.26), tricuspid annular planar systolic excursion (TAPSE) was unchanged (from 18.3 (11.9–24.5) to 20.5 (15.4–24.2) mm, p = 0.56) and right ventricular fractional area change (from 15.4 (11.1–35.6) to 31.2 (16.4–33.1)%, p = 0.09). At seven (1–13) days after thrombolysis, using dual energy computed tomography imaging ( n = 3), average relative peripheral lung enhancement increased from 12.6 to 21.6% ( p = 0.06). In conclusion, thrombolysis improved PaO2/FiO2 ratio and ventilatory ratio at 24 h as rescue therapy in patients with right ventricular dysfunction due to COVID-19-associated ARDS despite maximum therapy, as part of a multimodal approach, and warrants further study.
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27

Pareikaitė, Viktorija, Silvija Makrickaitė, and Giedrė Bakšytė. "Mechanical Mitral Valve Prosthesis Thrombosis: A Case Report." Acta medica Lituanica 32, no. 1 (2025): 131–36. https://doi.org/10.15388/amed.2025.32.1.13.

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Background: A rare but serious complication of heart valve replacement, prosthetic valve thrombosis carries significant risks of morbidity and mortality. Effective management depends on prompt diagnosis and the appropriate treatment, often involving fibrinolytic agents. Protocols using slower infusion rates and lower doses of these agents have led to improved therapy outcomes.Clinical case: We report a case of a 56-year-old man admitted to the Lithuanian University of Health Sciences Kaunas Clinics due to mechanical mitral valve prosthesis thrombosis complicated by a respiratory failure and atrial fibrillation. The patient was treated with ultraslow thrombolysis with alteplase. The function of the mechanical valve prosthesis became normal, and the patient was discharged from the hospital.Discussion and Conclusions: Managing prosthetic valve thrombosis is challenging due to overlapping clinical features with other diagnoses and the lack of consensus on the treatment methods. Slow-infusion, low-dose thrombolytic therapy with alteplase can be a life-saving intervention with a high success rate.
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28

Kohan, Marío R., Virginia Messler, Horacio Buffa, et al. "Reperfusion Times in a Telemedicine-guided Program for the Management of ST-segment Elevation Myocardial Infarction in the Province of La Pampa." Revista Argentina de Cardiologia 90, no. 4 (2022): 268–73. http://dx.doi.org/10.7775/rac.v90.i4.20536.

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Background: Timing of medical care is a relevant factor for ST-segment elevation myocardial infarction (STEMI) mortality. Objectives: The aim of the present study is to evaluate reperfusion times in STEMI patients participating in a telemedicine-based cardiology care program in the province of La Pampa between August 2018 and December 2021. Methods: This program consists of a protocol for the management of patients with acute coronary syndrome (ACS) in the different locations of the province, with 24-hour remote assistance provided by cardiologists, including both diagnostic support and coordination of on-site thrombolysis. Results: Of a total of 72 STEMI patients evaluated, 44 received thrombolysis as reperfusion therapy, 25 received primary percutaneous coronary intervention, and 3 received thrombolysis followed by rescue percutaneous coronary intervention. Of the 47 subjects who received thrombolysis, only 5 required to be transferred to the referral center for this procedure. Median door-to-needle time was 24 minutes and door-to balloon-time was 105 minutes. Twenty-eight percent of the subjects with primary percutaneous coronary intervention had a door-to-balloon time < 90 minutes and 53.2% of patients who received thrombolysis fulfilled a door-to-needle time < 30 minutes. Conclusions: The implementation of a telemedicine-guided program for decentralized management of STEMI patients was associated with a high percentage of compliance with the goals of implementing fibrinolytic-based reperfusion therapy
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29

M, Anupama, Sharath JV, and Shetty GG. "A study to compare fibrinolytic therapy versus primary percutaneous coronary intervention in ST-segment elevation myocardial infarction in a tertiary care hospital." National Journal of Physiology, Pharmacy and Pharmacology 13, no. 5 (2022): 1. http://dx.doi.org/10.5455/njppp.2023.13.09472202202102022.

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Background: ST-segment elevation myocardial infarction (STEMI) is the most dramatic manifestation of coronary artery disease, acute STEMI is a clinical syndrome defined by characteristic symptoms of myocardial ischemia in association with persistent electrocardiographic ST elevation and subsequent release of biomarkers of myocardial necrosis. Reperfusion with thrombolysis or PCI (percutaneous coronary intervention) is the current standard of care for STEMI. Aims and Objectives: The aim of the study was to compare the effectiveness of fibrinolytic therapy and primary PCI which are the available reperfusion strategies for STEMI. Materials and Methods: This prospective and observational study was conducted at a tertiary care hospital in Bangalore. Patients presenting with STEMI to emergency department were treated with either fibrinolysis or PCI as per protocol. Patients in each arm were followed up to know the differences in outcome at discharge and 30-day follow-up. Results: Patients admitted with STEMI had overall in hospital mortality of 17 (7.1%) patients, of which 9 (7.6%) patients were from fibrinolysis group and 8 (6.6%) patients from PCI group with no statistically significant difference (P = 0.760). There was significant incidence (P = 0.001) of reinfarct in fibrinolysis group (9.3%) when compared to PCI group (0%). Conclusion: There was no statistically significant mortality difference at discharge and at 30 day between fibrinolysis and primary PCI in patients with STEMI in our study, this may be attributed to use of rescue PCI in failed fibrinolysis patients and early tricuspid valve repair in many patients after fibrinolysis.
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30

Adzerikho, I. Е., V. E. Agabekov, Т. Е. Vladimirskaya, К. I. Dubatouka, and А. V. Zhilkevich. "Efficacy of a new system of targeted delivery of tenecteplase in acute myocardial infarction in an in vivo experiment." Proceedings of the National Academy of Sciences of Belarus, Medical series 21, no. 2 (2024): 116–24. http://dx.doi.org/10.29235/1814-6023-2024-21-2-116-124.

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A new system of targeted delivery of tissue plasminogen activator tenecteplase for restoration of coronary blood flow in acute myocardial infarction in animal experiments was developed.The new system of targeted delivery of fibrinolytic consists of native (“free”) and encapsulated (“bound”) tenecteplase in liposomes, in the percentage ratio (60 and 40 %, respectively), which are conjugated through carboxylated dextran with fibrin-specific monoclonal antibodies Fnl-3C.The physicochemical characteristics of the obtained liposomes conjugated with fibrin-specific monoclonal antibodies (immunoliposomes) with tenecteplase were determined: immunoliposomes have a hydrodynamic diameter of ~76‒77 nm, a zeta potential of ~(‒33) mV, a polydispersity index of ~0.55. Modification of liposomes with fibrin-specific monoclonal antibodies does not alter thrombolytic activity.When using immunoliposomes the survival rate of animals with acute myocardial infarction is ~90 %, liposomal and native form of the drug ‒ 80 %.The use of immunoliposomal delivery system in animals with acute myocardial infarction leads to an increase in the free lumen of the infarct-related artery (p < 0.05) by 26 % compared to the liposomal delivery system and by 46 % compared to native tenecteplase. At the same time, the mass of ischemic myocardium on the background of thrombolytic therapy with>< 0.05) by 26 % compared to the liposomal delivery system and by 46 % compared to native tenecteplase. At the same time, the mass of ischemic myocardium on the background of thrombolytic therapy with immunoliposomes decreases (p < 0.05) by 16 % in rats in comparison with the liposomal system and by 26 % in comparison with native tenecteplase. The new system of targeted delivery of tenecteplase provides effective and safe thrombolysis in animal experiment> < 0.05) by 16 % in rats in comparison with the liposomal system and by 26 % in comparison with native tenecteplase.The new system of targeted delivery of tenecteplase provides effective and safe thrombolysis in animal experiment.
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31

Haji Sobhani, Sepas, Mohammad Mahdi Daei, Samira Dodangeh, Majid Hajikarimi, and Navid Mohammadi. "Impact of Metabolic Syndrome in Patients With Acute Myocardial Infarction After Thrombolytic Therapy." Journal of Inflammatory Diseases 25, no. 4 (2022): 217–22. http://dx.doi.org/10.32598/jid.25.4.3.

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Background: Metabolic syndrome (MetS) comprises a group of conditions that happen together and increase the risk of heart disorders. MetS has known characteristic diagnostic criteria and is diagnosed through physical examination and blood tests. This syndrome is extremely prevalent in patients with acute myocardial infarction. We aimed to determine the prevalence of MetS and its relationship with myocardial infarction and response to treatment in patients suffering from acute myocardial infarction under fibrinolytic treatment. Methods: In this cross-sectional study, 145 patients with acute ST-elevation myocardial infarction (STEMI) were enrolled. They were referred to Bu-Ali Sina Hospital in Qazvin, Iran, between January 2018 and January 2019 and were candidates for thrombolytic therapy. The patients were divided into two groups with and without MetS according to the NCEP ATP III definition (the National Cholesterol Education Program-Adult Treatment Panel III). In each group, the ST resolution of more than 50% in electrocardiogram was evaluated 90 minutes after thrombolytic administration. In addition, angiographic information and left ventricular ejection fraction (LVEF) were compared between the two groups. Results: Overall, the prevalence of MetS was 57.2% in the study population. After treatment, ST-segment resolution of more than 50%, the number of involved coronary vessels, the thrombolysis in myocardial infarction flow grade, mean LVEF, and type of myocardial infarction were similar in both study groups. Conclusion: Our study indicates that MetS does not affect the response rate to thrombolytic treatment.
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32

Fraschini, G., J. Jadeja, M. Lawson, F. A. Holmes, H. C. Carrasco, and S. Wallace. "Local infusion of urokinase for the lysis of thrombosis associated with permanent central venous catheters in cancer patients." Journal of Clinical Oncology 5, no. 4 (1987): 672–78. http://dx.doi.org/10.1200/jco.1987.5.4.672.

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We assessed the efficacy of local fibrinolytic therapy in 35 axillary-subclavian vein thromboses (SVT) that occurred in cancer patients with percutaneous central venous catheters (CVC). These catheters were indwelling for a median of 1 month (range, one day to 10 months) before thrombosis developed. Urokinase was administered at a dose of 500 to 2,000 U/kg/h. Complete lysis occurred in 25 of 30 thrombi that were directly infused, after a median of four days. Complete lysis occurred in one of 12 thrombi that could not be directly infused with urokinase and in two of six with associated phlebitis. Eighty-one percent of the thrombi that were symptomatic for less than 1 week before treatment resolved, compared with 56% present for longer than 1 week. Sixteen patients who had complete (12) or partial (four) thrombolysis did not have their CVCs removed. All four patients with partial thrombolysis had recurrent thrombosis at a median of eight days (range, one to 90). Only two patients who had complete thrombolysis had recurrent thrombosis, at 8 and 16 months. Only minor hemorrhagic toxicity was seen.
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33

Liberale, Luca, Maria Bertolotto, Silvia Minetti, et al. "Recombinant Tissue Plasminogen Activator (r-tPA) Induces In-Vitro Human Neutrophil Migration via Low Density Lipoprotein Receptor-Related Protein 1 (LRP-1)." International Journal of Molecular Sciences 21, no. 19 (2020): 7014. http://dx.doi.org/10.3390/ijms21197014.

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Thrombolysis is the gold standard treatment for acute ischemic stroke. Besides its fibrinolytic role, recombinant tissue plasminogen activator (r-tPA) holds several non-fibrinolytic functions. Here, we investigated the potential role of r-tPA on human primary neutrophil migration in vitro. By means of modified Boyden chamber migration assay and checkerboard analysis we showed a dose-dependent chemotactic effect of r-TPA with a maximum effect reached by 0.03 mg/mL (0.003–1 mg/mL). Pre-incubation with MAP kinases inhibitors allowed the identification of PI3K/Akt, but not ERK1/2 as the intracellular pathway mediating the observed effects. Furthermore, by means of real-time PCR, immunocytochemistry and cytofluorimetry we demonstrated that the r-tPA receptor low density lipoprotein receptor-related protein 1 (LRP-1) is synthetized and expressed by neutrophils in response to r-tPA and TNF-α. Inhibition of LRP-1 by receptor-associated protein (RAP), prevented r-tPA-mediated F-actin polymerization, migration and signal through Akt but not ERK1/2. Lastly, also neutrophil degranulation in response to r-tPA seems to be mediated by LRP-1 under adhesion conditions. In conclusion, we show that r-tPA induces neutrophil chemotaxis through LRP-1/Akt pathway. Blunting r-tPA-mediated neutrophil activation might be beneficial as an adjuvant therapy to thrombolysis in this setting.
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34

Guimarães, Ana, Marrie Barrett-Bergshoeff, Marco Criscuoli, Stefano Evangelista, and Dingeman Rijken. "Fibrinolytic efficacy of Amediplase, Tenecteplase and scu-PA in different external plasma clot lysis models." Thrombosis and Haemostasis 96, no. 09 (2006): 325–30. http://dx.doi.org/10.1160/th06-04-0197.

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SummaryIn this study, the in-vitro fibrinolytic efficacy of Tenecteplase, Amediplase and scu-PA was investigated in different external lysis models by measuring the lysis of human plasma clots after the addition of the plasminogen activators (PAs) to the surrounding plasma. The effect ofTAFI was examined for each PA by neutralizing TAFI a with potato carboxypeptidase inhibitor (PCI). The lytic efficacy of Amediplase was lower than that of Tenecteplase at low PA concentrations but slightly higher at therapeutic concentrations. The activity of scu-PA was clearly lower than that of either Tenecteplase or Amediplase. The TAFI system inhibited external clot lysis mediated by all the PAs when thrombomodulin was present in the model. In the therapeutic range (5–10 µg/ml) however, the TAFIa effect was negligible for both Amediplase and Tenecteplase. At lower PA concentrations the effect of TAFI on Amediplase was slightly stronger than that on Tenecteplase. Under static conditions the lysis rates were lower than with stirring. The role of TAFI was similar under both conditions. In conclusion, at therapeutic concentrations Amediplase was slightly more active than Tenecteplase and scu-PA under all conditions used. Therefore, Amediplase might possibly be a more potent thrombolytic agent at these concentrations and increase the efficacy of thrombolysis. The potential of TAFI for inhibiting thrombolytic therapy is probably low. However in conditions where the local PA concentrations are sub-optimal TAFI might affect the lysis rate.
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35

Gu, Boram, Andris Piebalgs, Yu Huang, et al. "Mathematical Modelling of Intravenous Thrombolysis in Acute Ischaemic stroke: Effects of Dose Regimens on Levels of Fibrinolytic Proteins and Clot Lysis Time." Pharmaceutics 11, no. 3 (2019): 111. http://dx.doi.org/10.3390/pharmaceutics11030111.

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Thrombolytic therapy is one of the medical procedures in the treatment of acute ischaemic stroke (AIS), whereby the tissue plasminogen activator (tPA) is intravenously administered to dissolve the obstructive blood clot. The treatment of AIS by thrombolysis can sometimes be ineffective and it can cause serious complications, such as intracranial haemorrhage (ICH). In this study, we propose an efficient mathematical modelling approach that can be used to evaluate the therapeutic efficacy and safety of thrombolysis in various clinically relevant scenarios. Our model combines the pharmacokinetics and pharmacodynamics of tPA with local clot lysis dynamics. By varying the drug dose, bolus-infusion delay time, and bolus-infusion ratio, with the FDA approved dosing protocol serving as a reference, we have used the model to simulate 13 dose regimens. Simulation results are compared for temporal concentrations of fibrinolytic proteins in plasma and the time that is taken to achieve recanalisation. Our results show that high infusion rates can cause the rapid degradation of plasma fibrinogen, indicative of increased risk for ICH, but they do not necessarily lead to fast recanalisation. In addition, a bolus-infusion delay results in an immediate drop in plasma tPA concentration, which prolongs the time to achieve recanalisation. Therefore, an optimal administration regimen should be sought by keeping the tPA level sufficiently high throughout the treatment and maximising the lysis rate while also limiting the degradation of fibrinogen in systemic plasma. This can be achieved through model-based optimisation in the future.
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36

Koval, O. A., O. M. Klygunenko, and O. Yu Muryzina. "Coagulation properties of the blood coagulation system in acute pulmonary embolism and their dynamics against the background of systemic thrombolytic therapy for patients with different risk of hospital mortality." Ukrainian Journal of Cardiology 27, no. 1 (2020): 27–38. http://dx.doi.org/10.31928/1608-635x-2020.1.2738.

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The aim – to evaluate the dynamics of blood coagulation changes in patients with acute pulmonary embolism before and after systemic thrombolytic therapy (TLT), by comparing high and intermediate-high risk groups. Materials and methods. 45 patients, 29 male (62 %) and 17 female (38 %), 55.6±13.6 years old admitted into an intensive care unit with the first episode of acute PE and received systemic thrombolysis, were included into prospective nonrandomized investigation. Accoding to the ESC Guideline on pulmonary embolism (2014) these patients were split into two groups: unstable high-risk pulmonary embolism patients having or hypotension or episodes of syncope (group 1, n=28, 62 %), and patients with intermediate-high mortality risk with stable hemodynamic indexes (group 2, n=17, 38 %) but with massive bilateral embolism (U1-2=2.2, p=0.33), verified by multispiral computed tomography pulmonary angiography (angio-regimen), hemodynamically overload, with signs of right and ventricular dysfunction and positive troponin tests. The 30-day mortality risk for PESI corresponds to Grade V (IV): 152 ± 19 points in group 1, 138.0±9.7 in group 2 (p1-2<0.01). Results and discussion. In both groups, a similar (p1-2>0.25) initial procoagulant status was revealed by changes in thrombin formation indexes: prothrombin time (PT) increased to 19.8 [16, 23] sec, and prothrombin index increased to 96.1 % [86, 106], reduction of activated partial thromboplastin time to 23.5 [21, 24] sec. The content of the main coagulation substrate fibrinogen increased up to 4.3 [4.1, 4.5] g/l (p1-2=0.25), and markers of thrombinemia increased as follows: soluble fibrin up to 17.0 [16, 18] mg, D-dimer up to 5214 [3605, 5643] ng/ml. The systemic fibrinolytic activity was initially suppressed: the values of spontaneous fibrinolysis were reduced to 9.5 [6.0, 12.2] %, self-retraction – to 31.9 [26.1, 36.1] %. On the 5th day after the TLT on the background of basic therapy, the following dynamics was observed: increase of (Z=5.62, p<0.00001) activated partial thromboplastin time values – up to 46.1 ± 6.0 s (p1-2=0.36) and PT – up to 22.9 (18–26) s, while fibrinogen decreased – down to 3.5 g/l. Despite favorable changes, markers of thrombinemia remained increased: although fibrin values decreased (Z=3.03, p<0.001) to 13.7 mg, but still exceeded the upper limit of the reference range in both groups (p1-2=0.21). The values of spontaneous fibrinolysis increased to 11.9 % [9.9, 12.4], and self-retraction (Z=0.64, p<0.01) to 32.0 % [27.9, 33.0], remaining significantly lower than the reference level and indicating high risk of relapse of thromboembolic events. Conclusions. For patients with acute pulmonary embolism, regardless of the presence of high or intermediate-high risk, according to the main coagulation indexes, the procoagulant state of hemostasis, inhibition of fibrinolytic activity, decrease in clot density in vitro are identical in strength and direction. On the 5th day after TLT on the basic anticoagulation therapy and despite a certain level of therapeutic anticoagulation, a rather high level of markers of thrombinemia, inhibition of fibrinolysis and retraction persists. The presence of the same coagulation changes in strength and orientation, the depletion of fibrinolytic mechanisms of hemostasis, the positive clinical impact of TLT in the intermediate-high risk group supports indications for TLT in this group of patients.
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37

Taradin, G. G., G. A. Ignatenko, N. T. Vatutin, and I. V. Kanisheva. "CURRENT VIEW ON ANTICOAGULANT AND THROMBOLYTIC TREATMENT OF ACUTE PULMONARY EMBOLISM." Russian Archives of Internal Medicine 9, no. 5 (2019): 348–66. http://dx.doi.org/10.20514/2226-6704-2019-9-5-348-366.

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The presented review concerns contemporary views on specific aspects of anticoagulant and thrombolytic treatment of venous thromboembolism and mostly of acute pulmonary embolism. Modern classifications of patients with acute pulmonary embolism, based on early mortality risk and severity of thromboembolic event, are reproduced. The importance of multidisciplinary approach to the management of patients with pulmonary embolism with the assistance of cardiologist, intensive care specialist, pulmonologist, thoracic and cardiovascular surgeon, aimed at the management of pulmonary embolism at all stages: from clinical suspicion to the selection and performing of any medical intervention, is emphasized. Anticoagulant treatment with the demonstration of results of major trials, devoted to efficacy and safety evaluation of anticoagulants, is highlighted in details. Moreover, characteristics, basic dosage and dosage scheme of direct (new) oral anticoagulants, including apixaban, rivaroxaban, dabigatran, edoxaban and betrixaban are described in the article. In particular, the management of patients with bleeding complications of anticoagulant treatment and its application in cancer patients, who often have venous thromboembolism, is described. Additionally, modern approaches to systemic thrombolysis with intravenous streptokinase, urokinase and tissue plasminogen activators are presented in this review. The indications, contraindications, results of clinical trials devoted to various regimens of thrombolytic therapy, including treatment of pulmonary embolism by lower doses of fibrinolytic agents, are described.
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38

Spriggs, DJ, JM Stassen, Y. Hashimoto, and D. Collen. "Thrombolytic properties of human tissue-type plasminogen activator, single-chain urokinase-type plasminogen activator, and synergistic combinations in venous thrombosis models in dogs and rabbits." Blood 73, no. 5 (1989): 1207–12. http://dx.doi.org/10.1182/blood.v73.5.1207.1207.

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Abstract Thrombolysis with single and combined four-hour intravenous (IV) infusions of recombinant tissue-type plasminogen activator (rt-PA), recombinant single-chain urokinase-type plasminogen activator of 54,000 molecular weight (mol wt) (rscu-PA), and rscu-PA-32 kD, an rscu-PA derivative of 32,000 mol wt was studied in a femoral vein thrombosis model in the dog and in a jugular vein thrombosis model in the rabbit. In both species, the dose-response curves were linear, and no systemic activation of the fibrinolytic system or fibrinogen breakdown was observed. The steady-state levels of rt-PA-, rscu-PA-, and rscu-PA-32 kD-related antigens in plasma were proportional to the infusion rates. In the dog model, 25% lysis was obtained with 0.11 mg/kg rt-PA, 0.8 mg/kg rscu-PA, and 0.37 mg/kg rscu-PA-32 kD. Combinations of rt-PA and rscu-PA were 2.6 times more active (P less than .005) than anticipated on the basis of their pharmacologic additive effects, whereas combinations of rt-PA and rscu-PA-32 kD were 2.7 times more active (P less than .05). In the rabbit model, 25% lysis was obtained with 0.24 mg/kg rt-PA, 0.75 mg/kg rscu-PA, and 1.25 mg/kg rscu-PA-32 kD. Combinations of rt-PA and rscu-PA have a fivefold synergistic interaction, but surprisingly no synergism was observed between rt-PA and rscu-PA-32 kD. This study shows that synergism between rt-PA and rscu-PA occurs both in rabbits and dogs in a relatively narrow concentration range that allows a fractional reduction of the total equipotent dose by a factor of 2.5-fold to fivefold. Combination therapy is not associated with systemic fibrinolytic activation. This range of synergistic interaction, although limited, may be useful in devising the best thrombolytic therapy for patients with thromboembolic disease.
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39

Spriggs, DJ, JM Stassen, Y. Hashimoto, and D. Collen. "Thrombolytic properties of human tissue-type plasminogen activator, single-chain urokinase-type plasminogen activator, and synergistic combinations in venous thrombosis models in dogs and rabbits." Blood 73, no. 5 (1989): 1207–12. http://dx.doi.org/10.1182/blood.v73.5.1207.bloodjournal7351207.

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Thrombolysis with single and combined four-hour intravenous (IV) infusions of recombinant tissue-type plasminogen activator (rt-PA), recombinant single-chain urokinase-type plasminogen activator of 54,000 molecular weight (mol wt) (rscu-PA), and rscu-PA-32 kD, an rscu-PA derivative of 32,000 mol wt was studied in a femoral vein thrombosis model in the dog and in a jugular vein thrombosis model in the rabbit. In both species, the dose-response curves were linear, and no systemic activation of the fibrinolytic system or fibrinogen breakdown was observed. The steady-state levels of rt-PA-, rscu-PA-, and rscu-PA-32 kD-related antigens in plasma were proportional to the infusion rates. In the dog model, 25% lysis was obtained with 0.11 mg/kg rt-PA, 0.8 mg/kg rscu-PA, and 0.37 mg/kg rscu-PA-32 kD. Combinations of rt-PA and rscu-PA were 2.6 times more active (P less than .005) than anticipated on the basis of their pharmacologic additive effects, whereas combinations of rt-PA and rscu-PA-32 kD were 2.7 times more active (P less than .05). In the rabbit model, 25% lysis was obtained with 0.24 mg/kg rt-PA, 0.75 mg/kg rscu-PA, and 1.25 mg/kg rscu-PA-32 kD. Combinations of rt-PA and rscu-PA have a fivefold synergistic interaction, but surprisingly no synergism was observed between rt-PA and rscu-PA-32 kD. This study shows that synergism between rt-PA and rscu-PA occurs both in rabbits and dogs in a relatively narrow concentration range that allows a fractional reduction of the total equipotent dose by a factor of 2.5-fold to fivefold. Combination therapy is not associated with systemic fibrinolytic activation. This range of synergistic interaction, although limited, may be useful in devising the best thrombolytic therapy for patients with thromboembolic disease.
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40

Mair, Johannes, Erika Artner-Dworzak, Peter Lechleitner, et al. "Cardiac troponin T in diagnosis of acute myocardial infarction." Clinical Chemistry 37, no. 6 (1991): 845–52. http://dx.doi.org/10.1093/clinchem/37.6.845.

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Abstract Troponin T is a structurally bound protein found in striated muscle cells. We tested concentrations of its cardiac-specific isotype in peripheral venous blood samples serially drawn from 72 patients with confirmed myocardial infarction. Fifty-nine patients received thrombolytic treatment with intravenous streptokinase, urokinase, or recombinant tissue-type plasminogen activator; because of contraindications, the remaining 13 patients did not. Concentrations of troponin T in plasma, measured by an enzyme-linked immunosorbent assay, started increasing within a few hours after the onset of symptoms (median, 4 h; range, 1-10 h). The sensitivity of troponin T for detecting myocardial infarction was 100% from 10 to 120 h after the onset of symptoms; sensitivity on the seventh day after admission was 84%. Concentrations were increased for up to three weeks in some patients with late or high peak values. Successful reperfusion in Q-wave infarction obviously influences the release of troponin T into plasma, with all such cases showing peak values less than or equal to 26 h (median, 14 h) after the onset of symptoms. Troponin T concentrations in these patients returned to within the reference interval more rapidly than in nonreperfused subjects. In the 13 patients without fibrinolytic therapy, troponin T tended to peak approximately 48 h (median) after the onset of chest pain. Troponin T concentrations in patients for whom thrombolysis was unsuccessful resembled those in patients without fibrinolytic therapy. The specificity of the assay was 96% as tested in samples of 96 emergency-room patients. The reference interval (less than 0.5 micrograms/L) was established from samples of 100 healthy blood donors. Troponin T measurements are a specific and sensitive method for the early and late diagnosis of acute myocardial infarction and could, therefore, provide a new criterion in laboratory diagnosis of its occurrence.
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41

Berridge, D. C., J. J. Earnshawl, J. C. Westby, G. S. Makin, and B. R. Hopkinson. "Fibrinolytic Profiles in Local Low-Dose Thrombolysis with Streptokinase and Recombinant Tissue Plasminogen Activator." Thrombosis and Haemostasis 61, no. 02 (1989): 275–78. http://dx.doi.org/10.1055/s-0038-1646575.

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SummaryFibrinolytic parameters have been monitored in 44 patients undergoing local low-dose intra-arterial thrombolysis for acute peripheral arterial ischaemia. Streptokinase (Sk), at a dose of 5,000 units/hr with 250 units/hr heparin, was used in 23 patients and recombinant tissue plasminogen activator (r-tPA) at a dose of 0.5 mg/hr was used in 21 patients. Successful lysis was seen in 18 (86%) patients following r-tPA and in 15 (65%) patients following streptokinase. There were 4 minor haematomas in each group usually at the catheter entry site. Both agents produced a systemic effect, which was still seen 12 hours post-infusion. However, that produced by r-tPA was delayed and significantly reduced compared to that produced by Sk.These results confirm the relative fibrin specificity of r-tPA. When used as a continuous low-dose intra-arterial infusion, r-tPA offers a significantly lower, potentially safer, systemic effect than conventional therapy with streptokinase.
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42

Zou, Lili, Hui Liang, LI Hou, et al. "Neutrophil Extracellular Traps Promote Hypercoagulability in ST-Elevated Myocardial Infarction Following Fibrinolytic Administration." Blood 132, Supplement 1 (2018): 3797. http://dx.doi.org/10.1182/blood-2018-99-116105.

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Abstract Introduction:Fibrinolysis plays an important role in the treatment of ST-elevated myocardial infarction (STEMI) when percutaneous coronary intervention is not readily available. Early and successful myocardial reperfusion with thrombolytic therapy effectively reduces the infarct size and improves the clinical outcome. However, the process of restoring blood flow to the ischemic myocardium can induce injury and reduce the beneficial effects of myocardial reperfusion. Previous studies had shown that platelets, leukocytes and TF play important role in thrombotic complications after fibrinolysis in AMI. However, there are still 10-15% patients who have risk for re-occlusion after antiplatelet and anticoagulant therapies. Thus, we speculate that there may be other mechanisms involved in the hypercoagulability after STEMI fibrinolysis. Neutrophil extracellular traps (NETs) are double-edge swords that could ensnare and kill microbial pathogens but also contribute to thrombosis. However, the role of NETs during STEMI fibrinolysis-induced re-occlusion is largely unknown. Our aims were to determine the procoagulant role of NETs after successful thrombolysis, and to elucidate its interaction with endothelial cells (ECs). Methods:31 STEMI patients with successfully fibrinolysis and 12 healthy controls were enrolled. Patient blood samples were collected at 0 h, 2 h, 6 h, 12 h and 24 h after fibrinolysis. Cell-free DNA (cf-DNA) was quantified using the Quant-iT PicoGreen dsDNA Assay Kit. ELISA was used to detect MPO-DNA complexes and TAT (thrombin-antithrombin) complexes. Wright-Giemsa and immunofluorescence confocal microscope were used to analyze and quantify NETs formation in neutrophil cells. ECs were incubated in growth media containing 20% pooled serum obtained from healthy donors in the presence or absence of 20-fold concentrated neutrophil extracellular chromatin. The procoagulant activity (PCA) of neutrophils and ECs was measured by clotting time and purified coagulation complex assays. DNase I or anti-TF were included in the inhibition assays. Results: We found that cf-DNA, MPO-DNA and TAT are significantly reduced at 2 hours in STEMI patients with successful fibrinolysis. Their levels then increased and peaked at 6 hours (Figure 1A, B, E). Interestingly, the level of cf-DNA at 6 hours in STEMI thrombotic patients was positively correlated with TAT (r=0.959; p<0.01; Figure 1G). Wright-Giemsa and immunofluorescence staining showed that NETs were released by STEMI reperfusion neutrophils or by control neutrophils treated with plasma obtained from STEMI patients with fibrinolysis (Figure 1D,F), and the percentage of NETs-releasing PMNs was about 30% (Figure 1C). Isolated neutrophils from fibrinolytic patients in vitro demonstrated significantly shortened coagulation time and increased fibrin formation after 2 hours fibrinolysis, and peaked at 6 hours. DNase I but not anti-tissue factor antibody could inhibit these effects. Co-incubation assays revealed that NETs triggered PS exposure on ECs, converting them to a procoagulant phenotype. Confocal imaging of NETs-treated ECs illustrated that bound FVa and FXa colocalized within PS-enriched areas of ECs to form prothrombinase, and further supported fibrin formation. Moreover, patients with recurrent ischemia showed significantly higher NETs release and thrombin generation than non-recurrent ischemia. Conclusions: Our study reveals that the PCA of STEMI following fibrinolytic administration decrease after 2 hours, then increase and peak at 6 hours, which is at least partly due to the release of NETs induced by activated PMNs. Additionally, NETs partly contribute to ECs injury after myocardial reperfusion. DNase I can disconnect NETs and may therefore serve as a promising therapeutic target in STEMI reinfarction and recurrent ischemia. Disclosures No relevant conflicts of interest to declare.
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43

Valeria, Peralta Ugalde, Yalharahi Naif Mendoza Valeria, Alfonso Vargas Moreno Iván, et al. "Pulmonary Embolism with Thrombus in Transit Case Report." INTERNATIONAL JOURNAL OF MEDICAL SCIENCE AND CLINICAL RESEARCH STUDIES 03, no. 08 (2023): 1710–14. https://doi.org/10.5281/zenodo.8278397.

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A clinical case is presented at the Hospital Centenario Miguel Hidalgo with a diagnosis of pulmonary thromboembolism with a thrombus in transit and dysfunction of the right cavities, secondary to immobilization due to a history of previous spinal surgery as an ankylosing spondylitis treatment. He was admitted to the emergency room with typical symptoms of the entity, evidenced by angiotomography, later a transthoracic echocardiogram was performed, presenting the characteristic echocardiographic signs of right ventricular dysfunction and evidence of mobile thrombus in the right cavities, for which reason fibrinolytic therapy was decided with success, evidenced in transthoracic echocardiography with improvement of ventricular systolic function and strain.
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44

D’Aprile, Anna, Alessandra Italia, Paolo Gresele, John Morser, Nicola Semeraro, and Mario Colucci. "Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Does not Inhibit In Vitro Thrombolysis by Pharmacological Concentrations of t-PA." Thrombosis and Haemostasis 85, no. 04 (2001): 661–66. http://dx.doi.org/10.1055/s-0037-1615650.

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SummaryTAFI (thrombin activatable fibrinolysis inhibitor) is a plasma procarboxypeptidase that upon activation inhibits the fibrinolytic process by removing the C-terminal lysines from partially degraded fibrin. The generation of activated TAFI (TAFIa) has been suggested to represent a mechanism of thrombus resistance to thrombolytic therapy. However, the ability of TAFI to inhibit fibrinolysis by pharmacological concentrations of t-PA has not been properly investigated. We used an in vitro model consisting of 125I-fibrin blood clots submerged in auto-logous defibrinated plasma. Upon addition of t-PA (125-5000 ng/ml) and CaCl2 (25 mM), samples were incubated at 37° C, and clot lysis was measured at intervals from the radioactivity released into solution. The role of TAFI was assessed either by neutralizing the generated TAFIa with the specific inhibitor PTI (50 g/ml) or by enhancing TAFI activation through the addition of recombinant soluble thrombomodulin (solulin, 1 μg/ml). In our clot lysis model, activation of TAFI amounted to about 20% of inducible carboxypeptidase activity. Addition of PTI, however, produced a significant increase in the extent of lysis only at concentrations of t-PA equal to or lower than 250 ng/ml. When solulin was added to the plasma surrounding the clot, about 70% of TAFI was activated within 15 min. Under these conditions, inhibition of clot lysis was very marked in samples containing 125 or 250 ng/ml of t-PA, but negligible in those containing pharmacological concentrations of the activator (1000 and 5000 ng/ml). Additional experiments suggest that loss of fibrin-dependence by elevated concentrations of t-PA may be one of the mechanisms explaining the lack of effect of TAFIa. Our data indicate that, under our experimental conditions, clot lysis by pharmacological concentrations of t-PA is not influenced by TAFIa even after maximal activation of this procarboxypeptidase.
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45

Norkienė, Ieva, Ieva Kažukauskienė, Robertas Samalavičius, and Kęstutis Ručinskas. "Successful application of thrombolysis and angioplasty in case of mechanical aortic valve and coronary graft thrombosis." Acta medica Lituanica 23, no. 1 (2016): 1–4. http://dx.doi.org/10.6001/actamedica.v23i1.3263.

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Prosthetic valve thrombosis (PVT) is a rare and fatal complication requiring immediate treatment. Optimal management of the left-sided obstructive PVT is still controversial and depends on patient’s status, estimated risk of surgery, thrombus location and size, and clinician’s experience. We report a case of a 71-year-old woman, presenting with signs of cardiogenic shock. Transesophageal echoscopy was used to diagnose acute obstructive thrombosis of the mechanical aortic valve. Concomitant coronary graft thrombosis was suspected due to signs of acute myocardial infarction. Thrombolysis with alteplase and subsequent stenting of the venous graft lead to successful resolution of the thrombotic lesions and a favourable patient outcome. Fibrinolytic therapy followed by angioplasty is a rational treatment alternative for inoperable or high risk patients in the case of concomitant mechanical valve and graft thrombosis.
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46

Zabolotnyi, Dmitry, Volodymyr Chernyshenko, Tetiana Shydlovska, Diana Zabolotna, Yevhenii Stohnii, and Serhij Verevka. "NON-PLASMIN-THROMBOLYTICS: NECESSITY, OPPORTUNITIES AND PROSPECTS (review of literature data and own research)." JOURNAL OF THE NATIONAL ACADEMY OF MEDICAL SCIENCES OF UKRAINE, no. 1 2022 (June 30, 2022): 293–305. http://dx.doi.org/10.37621/jnamsu-2022-1-1.

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State of the problem. Thrombotic complications are a common risk factor for a variety of diseases and are one of the leading causes of death. This leads to a strong interest in finding effective means of prevention and treatment. A characteristic feature of the last decade is the growing interest and numerous attempts to introduce into clinical practice fibrinolytic enzymes that are not functionally related to the hemostasis system. The aim of the work. Investigation of molecular mechanisms that cause the lack of efficiency of native fibrinolysis in relation to fibrin clots with impaired regularity of fibrin structure. Correlation of own achievements in the field of biochemistry and medicine with systematized literary material. The possibilities created by non-plasmin fibrinolytics and the advantages of their use are considered. Discussion and conclusions. The reasons of the complications caused by insufficient efficiency of both own fibrinolytic system, and the entered fibrinolytics are substantiated. It is shown that the leading role in such complications is played by violation of the regularity of the structure of fibrin clots. The mechanisms of action of leading fibrinolytic agents are considered and the expediency of using alternative non-plasmin fibrinolytics is substantiated. The properties and expediency of the use of fibrinolytics based on components of snake venoms and bacterial proteinases as effective means for the breakdown of fibrin with impaired regularity of structure are discussed. Key words: fibrosis, thrombotic therapy, fibrinolytic enzymes, hemostasis system.
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47

Baker, William F. "Thrombosis and Hemostasis in Cardiology: Review of Pathophysiology and Clinical Practice (Part I)." Clinical and Applied Thrombosis/Hemostasis 4, no. 1 (1998): 51–75. http://dx.doi.org/10.1177/107602969800400107.

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The adverse consequences of thrombosis are per haps nowhere more evident than in clinical cardiology. Throm bosis and hemostasis are primary issues in the management of patients with atrial fibrillation, prosthetic heart valves, severe left ventricular dysfunction, and coronary artery disease. Clini cal trials have defined a crucial role for anticoagulation with warfarin in patients with atrial fibrillation to reduce the inci dence of stroke. Anticoagulation with warfarin and aspirin in combination offers significant protection from systemic emboli in patients with mechanical prosthetic valves, without a sub stantial increased risk of hemorrhage. The risk of systemic emboli may also be reduced by anticoagulation in patients with severe left ventricular dysfunction. Disturbance of the normal balance of hemostasis is a major factor in the pathophysiology of coronary artery disease. Antiplatelet therapy, antithrombin agents, anticoagulants, and fibrinolytic agents have been used to prevent and treat acute coronary thrombosis and to prevent reocclusion following thrombolysis and interventional therapy. Guidelines are presented for antithrombotic therapy in the prac tice of clinical cardiology.
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48

Baker, William F. "Thrombosis and Hemostasis in Cardiology: Review of Pathophysiology and Clinical Practice (Part II)." Clinical and Applied Thrombosis/Hemostasis 4, no. 2 (1998): 143–47. http://dx.doi.org/10.1177/107602969800400214.

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The adverse consequences of thrombosis are per haps nowhere more evident than in clinical cardiology. Throm bosis and hemostasis are primary issues in the management of patients with atrial fibrillation, prosthetic heart valves, severe left ventricular dysfunction, and coronary artery disease. Clini cal trials have defined a crucial role for anticoagulation with warfarin in patients with atrial fibrillation to reduce the inci dence of stroke. Anticoagulation with warfarin and aspirin in combination offers significant protection from systemic emboli in patients with mechanical prosthetic valves, without a sub stantial increased risk of hemorrhage. The risk of systemic emboli may also be reduced by anticoagulation in patients with severe left ventricular dysfunction. Disturbance of the normal balance of hemostasis is a major factor in the pathophysiology of coronary artery disease. Antiplatelet therapy, antithrombin agents, anticoagulants, and fibrinolytic agents have been used to prevent and treat acute coronary thrombosis and to prevent reocclusion following thrombolysis and interventional therapy. Guidelines are presented for antithrombotic therapy in the prac tice of clinical cardiology. Key Words: Thrombosis— Cardiology—Coronary artery disease—Atrial fibrillation— Valvular heart disease.
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49

Crabbe, Sarah J., Aileen M. Grimm, and Leigh E. Hopkins. "Acylated Plasminogen‐Streptokinase Activator Complex: A New Approach to Thrombolytic Therapy." Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 10, no. 2 (1990): 115–26. http://dx.doi.org/10.1002/j.1875-9114.1990.tb02559.x.

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Acylated plasminogen‐streptokinase activator complex (APSAC; anistreplase) is an inactive complex of human plasminogen and streptokinase. When it is injected, a controlled deacylation of the catalytic center occurs, activating the complex so that thrombolysis may begin. This process extends the half‐life of streptokinase, allowing for 4–6 hours of fibrinolytic activity. Anistreplase has demonstrated equivalent efficacy to intracoronary streptokinase with regard to reperfusion rates in acute myocardial infarction. In addition, patients have shown a 56% reduction in mortality at 28 days with anistreplase compared to heparin. The adverse effect profile of anistreplase includes minor bleeding and hematoma formation at the site of venipuncture, hypotensive and bradycardic episodes, arrhythmias, facial flushing, fever, and rarely, allergic reactions. Serious bleeding reactions are uncommon, with the frequency of cerebrovascular accident reported at 0.4‐0.6%. The special advantage of anistreplase is its administration as a 30‐U intravenous bolus injected over 5 minutes, eliminating the need for long infusions and increasing the ease of administration. Based on its efficacy and ease of administration, anistreplase may become the drug of choice in the emergency treatment of acute myocardial infarction.
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50

Leach, J., Eugene Patterson, and Edgar O’Rear. "Encapsulation of a plasminogen activator speeds reperfusion, lessens infarct and reduces blood loss in a canine model of coronary artery thrombosis." Thrombosis and Haemostasis 91, no. 06 (2004): 1213–18. http://dx.doi.org/10.1160/th03-11-0704.

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SummaryIn the present study, a polymer-encapsulated plasminogen activator was investigated as an alternative to restore blood flow more effectively than free plasminogen activator. While current fibrinolytic agents have limited efficacy, attributable to delayed onset of sustained reperfusion and bleeding complications, encapsulated plasminogen activators have shown promise in addressing these shortcomings. A polymer-encapsulated plasminogen activator could offer an effective formulation with a prolonged shelf-life. In this study, coronary artery thrombosis was produced in the anesthetized dog by the injection of thrombin + whole blood, and then one of five randomly selected formulations was administered intravenously: saline, blank microcapsules, free streptokinase (FREE SK), streptokinase and blank microcapsules (FREE SK + BLANK), or streptokinase entrapped in polymer microcapsules (MESK). MESK significantly accelerated the time to reperfusion compared to FREE SK or FREE SK + BLANK. Additionally, substantial reductions were observed in residual clot mass, infarct mass, reocclusion episodes, fibrinogen depletion and blood loss with MESK compared to FREE SK. The results of this study demonstrate that MESK accelerates thrombolysis and the restoration of blood flow compared to identical dosages of FREE SK while also reducing systemic fibrinogenolysis and blood loss. Microencapsulation may produce an improved dosage form for restoring arterial blood flow and reducing bleeding complications with thrombolytic therapy.
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