Fibrinolytic Drugs Research Articles

Microdosing of alteplase leads to thrombolysis in an in vitro flow model of cardiac microvascular obstruction

Abstract Background Cardiac microvascular obstruction (MVO) is a frequent injury of the myocardial microcirculation after successful recanalisation of the occluded coronary artery in myocardial infarction. At least in part, MVO is caused by embolised microthrombi of less than 200 µm diameter [1]. MVO leads to hypoperfusion of the myocardium and negatively affects patient outcomes. However, there is no effective treatment for MVO [2, 3]. Thrombolytic drugs are a promising approach, but they are difficult to deliver to the MVO area, and an increased risk of bleeding limits their use. In a previous study using an in vitro fluidic multi-scale model for MVO [4, 5], it was shown that controlled flow infusion (CFI) with a novel drug-delivering catheter could be used to effectively deliver highly concentrated intracoronary microdoses of a thrombolytic drug to the MVO area [6]. We now aim to investigate how such locally administered drug microdoses can induce thrombolysis as a possible therapeutic approach for MVO treatment. Methods A microfluidic chip (Fig.1) was used to study thrombolysis under flow using different microdoses of the thrombolytic drug alteplase. The chip consists of a tapered straight channel, which traps injected porcine microthrombi without causing complete channel occlusion (Fig. 1A). To mimic intracoronary CFI (consisting of temporary balloon occlusion of a coronary vessel for 90 seconds while drug is injected distally through a catheter) in vitro, microthrombi were incubated (without flow) directly in the chip for 90 seconds with various microdoses of alteplase (Fig. 2A, C). The chip was subsequently perfused with porcine plasma for 25 min (matched for physiological shear stress of 30 dyn/cm²). Conventional intravenous (IV) drug infusion (10 mg dose) resulting in a low systemic alteplase concentration, was mimicked by perfusing microthrombi with porcine plasma containing 2 µg/ml alteplase (Fig. 2B, C). Results Thrombolysis after CFI was concentration dependent, with the lowest microdose (0.3 mg) achieving 24% lysis of the thrombus area and the highest microdose (1.5 mg) achieving 60% lysis. In contrast, conventional IV drug infusion (corresponding to 10 mg alteplase IV dose) only achieved 10% lysis and was not significantly higher than the control perfused with pure porcine plasma. Conclusion Our findings suggest that intracoronary CFI is more efficient at achieving porcine microthrombus lysis than the current standard of IV bolus infusion (2 µg/ml alteplase in the circulating blood). Intracoronary CFI microdosing of fibrinolytic drugs using a drug-delivering catheter is a promising therapeutic approach for treating embolising MVO with a reduced systemic drug burden. Importantly, our intracoronary CFI approach achieves locally 6–40 times higher drug concentrations than a conventional IV drug infusion while reducing the total drug dose 60–300 times (Fig. 2C).

Development of a Methodology Based on Optical Interferometry for Measuring Fibrinolytic Activity.

Fibrinolytic activity assay is particularly important for the detection, diagnosis, and treatment of cardiovascular disease and the development of fibrinolytic drugs. A novel efficacious strategy for real-time and label-free dynamic detection of fibrinolytic activity based on ordered porous layer interferometry (OPLI) was developed. Fibrin or a mixture of fibrin and plasminogen (Plg) was loaded into the highly ordered silica colloidal crystal (SCC) film scaffold to construct a fibrinolytic response interference layer to measure fibrinolytic activity with different mechanisms of action. Fibrinolytic enzyme-triggered fibrinolysis led to the migration of interference fringes in the interferogram, which could be represented by optical thickness changes (ΔOT) tracked in real time by the OPLI system. The morphology and optical property of the fibrinolytic response interference layer were characterized, and the Plg content in the fibrinolytic response interference layer and experimental parameters of the system were optimized. The method showed adequate sensitivity for the fibrinolytic activity of lumbrokinase and streptokinase, with wide linear ranges of 12-6000 and 10-2000 U/mL, respectively. Compared with the traditional fibrin plate method, it has a lower detection limit and higher linearity. The whole kinetic process of fibrinolysis by these two fibrinolytic drug models was recorded in real time, and the Michaelis constant and apparent kinetic parameters were calculated. Importantly, some other blood proteins were less interfering with this system, and it showed reliability in fibrin activity detection in real whole blood samples. This study established a better and more targeted research method of in vitro fibrinolysis and provided dynamic monitoring data for the analysis of fibrinolytic activity of whole blood.

The Use of Fibrinolytic Agents in the Salvage of Free Flaps: A Systematic Review.

Microvascular thrombosis following free tissue transfer presents a complex challenge for surgeons and carries the potential risk of flap failure. The application of fibrinolytic agents represents a robust therapeutic option. The aim of this systematic review is to provide a comprehensive overview of the clinical use of fibrinolytic drugs in the rescue of compromised free flaps. A systematic literature search for clinical studies detailing the utilization of fibrinolytic agents for salvaging free flaps was conducted using the PubMed and Web of Science databases. The inclusion criteria encompassed English-language publications that specifically addressed the clinical application of fibrinolytic agents for free-flap salvage. A total of 331 articles were screened after excluding duplicates, with 56 meeting the inclusion criteria. Among these, 21 were clinical trials (evidence level III), and 35 were case studies (evidence level IV/V). In total, 459 flaps underwent treatment with fibrinolytic agents. The application of fibrinolytic agents appears to be a valuable intervention for rescuing compromised free flaps attributable to microvascular compromise. Notably, no prospective randomized trials have been published on this subject, and the evidence within the existing literature is characterized by its limited and heterogeneous nature. Further research is imperative to gather data on the efficacy, dosage, and safety profile of fibrinolytic agents.

A retrospective study to evaluate the safety and efficacy of intrapleural alteplase in pediatric empyema.

Medical treatment of pediatric empyema consists of appropriate antibiotics, chest tube insertion, and intrapleural fibrinolytic drugs to facilitate pleural drainage. There is a lack of consensus about the drug of choice for fibrinolytic therapy, so this study was designed to evaluate the safety and efficacy of intrapleural alteplase in pediatric empyema. The medical records of all children with empyema treated with intrapleural alteplase at a university hospital between January 2016 and December 2020 were retrospectively reviewed. Efficacy outcomes were assessed by chest tube output before and after the first dose of alteplase, pleural fluid volume before and after therapy, a need for surgical intervention, and length of hospital stay. Safety was assessed by the frequency and severity of side effects. 40 children aged 2 months to 9 years hospitalized with empyema received intrapleural alteplase. Thirty patients (75%) experienced full recovery after three doses of intrapleural alteplase. The median length of hospital stay was 16 days. Chest tube output increased significantly after the first dose of alteplase. Pleural fluid volume decreased significantly after treatment. The most common side effect was pain (30%). Two patients experienced severe complications: 1 had a pulmonary hemorrhage and the other experienced a bronchopleural fistula. These patients recovered fully spontaneously. According to our results, the administration of intrapleural alteplase was safe and effective in facilitating pleural drainage in pediatric patients with empyema. However, further clinical trials will be needed to determine the optimal dose, frequency, and duration of intrapleural alteplase treatment.

A low bleeding risk thrombolytic agent: citPA5.

Alteplase is a cornerstone thrombolytic agent in clinical practice but presents a potential bleeding risk. Stroke patients need pre-screening to exclude haemorrhagic stroke before using alteplase. In this study, we develop a new thrombolytic agent citPA5, characterized by an enhanced safety profile and minimal bleeding tendency. A clot lysis agent, named citPA5, is developed based on rtPA with point mutations to completely suppress its proteolytic activity in the absence of fibrin. In the presence of fibrin, citPA5 exhibited significantly higher fibrinolytic activity (a 15.8-fold increase of kcat/Km). Furthermore, citPA5 showed resistance to endogenous fibrinolysis inhibitor, PAI-1, resulting in enhanced potency. In a series of safety evaluation experiments, including thrombelastography assay, mice tail bleeding assay, and a murine intracerebral haemorrhage (ICH) model, citPA5 did not cause systemic bleeding or worsen ICH compared with alteplase. This highlights the low risk of bleeding associated with citPA5. Finally, we found that citPA5 effectively improved cerebral blood flow and reduced infarct volume in a carotid embolism-induced stroke model. This clot lysis agent, citPA5, not only exhibits a low risk of bleeding but also demonstrates highly effective thrombolysis capabilities. As a result, citPA5 shows great potential for administration prior to the classification of stroke types, making it possible for use in ambulances at the onset of stroke when symptoms are identified. The findings presented in this study also suggest that this strategy could be applied to develop a new generation of fibrinolytic drugs that offer greater safety and specificity in targeting fibrin.

Thrombolytic therapy based on lyophilized platelet-derived nanocarriers for ischemic stroke

BackgroundIntravenous administration of fibrinolytic drugs, such as recombinant tissue plasminogen activator (rtPA) is the standard treatment of acute thrombotic diseases. However, current fibrinolytics exhibit limited clinical efficacy because of their short plasma half-lives and risk of hemorrhagic transformations. Platelet membrane-based nanocarriers have received increasing attention for ischemic stroke therapies, as they have natural thrombus-targeting activity, can prolong half-life of the fibrinolytic therapy, and reduce side effects. In this study we have gone further in developing platelet-derived nanocarriers (defined as cellsomes) to encapsulate and protect rtPA from degradation. Following lyophilization and characterization, their formulation properties, biocompatibility, therapeutic effect, and risk of hemorrhages were later investigated in a thromboembolic model of stroke in mice.ResultsCellsomes of 200 nm size and loaded with rtPA were generated from membrane fragments of human platelets. The lyophilization process did not influence the nanocarrier size distribution, morphology, and colloidal stability conferring particle preservation and long-term storage. Encapsulated rtPA in cellsomes and administered as a single bolus showed to be as effective as a continuous clinical perfusion of free rtPA at equal concentration, without increasing the risk of hemorrhagic transformations or provoking an inflammatory response.ConclusionsThis study provides evidence for the safe and effective use of lyophilized biomimetic platelet-derived nanomedicine for precise thrombolytic treatment of acute ischemic stroke. In addition, this new nanoformulation could simplify the clinical use of rtPA as a single bolus, being easier and less time-consuming in an emergency setting than a treatment perfusion, particularly in stroke patients. We have successfully addressed one of the main barriers to drug application and commercialization, the long-term storage of nanomedicines, overcoming the potential chemical and physical instabilities of nanomedicines when stored in an aqueous buffer.

Role of factor XIII in ischemic stroke: a key molecule promoting thrombus stabilization and resistance to lysis

BackgroundActive coagulation factor XIII (FXIII) catalyzing crosslinking of fibrin and other hemostatic factors plays a key role in clot stability and lysis. ObjectivesTo evaluate the effect of FXIII inhibition in a mouse model of ischemic stroke (IS) and the role of activated FXIII (FXIIIa) in clot formation and lysis in patients with IS. MethodsA ferric chloride IS murine model was performed before and after administration of a FXIIIa inhibitor (FXIIIinh). Thromboelastometry in human and mice blood was used to evaluate thrombus stiffness and lysis with FXIIIinh. FXIIIa-dependent fibrin crosslinking and lysis with fibrinolytic drugs (tissue plasminogen activator and tenecteplase) were studied on fibrin plates and on thrombi and clotted plasma of patients with IS. Finally, circulating and thrombus FXIIIa were measured in 85 patients with IS. ResultsFXIIIinh administration before stroke induction reduced infarct size, α2-antiplasmin (α2AP) crosslinking, and local microthrombosis, improving motor coordination and fibrinolysis without intracranial bleeds (24 hours). Interestingly, FXIII blockade after stroke also reduced brain damage and neurologic deficit. Thromboelastometry in human/mice blood with FXIIIinh showed delayed clot formation, reduced clot firmness, and shortened tissue plasminogen activator lysis time. FXIIIa fibrin crosslinking increased fibrin density and lysis resistance, which increased further after α2AP addition. FXIIIinh enhanced ex vivo lysis in stroke thrombi and fibrin plates. In patients with IS, thrombus FXIII and α2AP were associated with inflammatory and hemostatic components, and plasma FXIIIa correlated with thrombus α2AP and fibrin. ConclusionOur results suggest a key role of FXIIIa in thrombus stabilization, α2AP crosslinking, and lysis resistance, with a protective effect of FXIIIinh in an IS experimental model.

Sequential intrapleural administration of fibrinolytic drugs and dornase alfa for empyema management. Treatment protocol based on its physicochemical stability

ObjectiveIntrapleural administration of fibrinolytics and dornase alfa has been shown in randomized studies to be able to reduce both the need for surgical debridement of empyema and the average hospital stay. However, its application in clinical practice is limited, probably due to the lack of protocols that simplify its administration. The present study aims to analyze the physicochemical stability of the simultaneous urokinase and dornase alfa administration for the subsequent development of a clinical practice use protocol. MethodIn vitro stability test of urokinase, dornase alfa and a combination of both. Its stability was evaluated as (i) absence of particles, (ii) color variation and (iii) pH changes at times 0, 30 minutes, 1, 2 and 4 hours at 37 °C. Each sample was prepared and analyzed in triplicate. ResultsIndividual solutions of urokinase and dornase alfa showed slight changes in pH, finding no changes in either color or presence of suspended particles. The urokinase and dornase alfa combination was not stable after 2 hours, when turbidity emerged due to flocculation and phase separation. After 4 hours, precipitate formation was found. A protocol for clinical use was developed based on urokinase and dornase alfa sequential administration, since it was not possible to guarantee the physicochemical stability of the simultaneous administration of both drugs. ConclusionsThe physicochemical stability data obtained does not allow to ensure a simultaneous administration of both drugs in a safe and effective way, thus a sequential administration protocol is proposed.

PB0364 Glycoprotein VI-Targeted Antiplatelet Therapy with Glenzocimab is Safe in Patients Exposed to Current Antithrombotic and Fibrinolytic Drugs

PB0364 Glycoprotein VI-Targeted Antiplatelet Therapy with Glenzocimab is Safe in Patients Exposed to Current Antithrombotic and Fibrinolytic Drugs

Potensi Ekstrak Enzim Daun Pepaya (Carica papaya L.) Sebagai Agen Fibrinolitik Dengan Metode Clot Lysis in Vitro

Stroke is a disease caused due to blockage of blood vessels. Health department in 2013 stated that 15,4% of people died from strokes. One of the treatment therapies that can be used is fibrinolytic. Fibrinolytic agents have a role in lysing blood clots, these agents can be obtained from microbes, plants and animals. This study aims to determine the protein content contained in papaya leaf enzyme extract (Carica papaya L.), and to determine the potential of the enzyme extract at certain concentrations as an alternative to natural fibrinolytic drugs. The study began with plant determination, sampling, enzyme extraction using a blender, purification of the extract by precipitation using ammonium sulphate, protein content determination using the Lowry method, and testing the fibrinolytic activity of the clot lysis method in vitro. Three series of test concentrations were made, namely 20, 40, and 80%. The results of the research on papaya leaf extract showed that the protein content in purification pellet 1 was 196,22 µg/ml and purification pellet 2 was 306,33 µg/ml. In papaya leaves, fibrinolytic activity was proven with the optimal percentage of blood clot lysis in purification pellet 2 with a concentration of 80% which was 79%.

Intrapleural Streptokinase in Management of Multiloculated Pleural Effusion as a Complication of Frequent Relapse Nephrotic Syndrome - A Case Report

Treatment of pleural effusion with intrapleural administration of fibrinolytic drugs has proven to be efficient and secure. Patients with pleural effusion who receive streptokinase instillations in conjunction with chest tube draining avoid surgery and have better outcomes. Its application in multiloculated pleural effusion, which develops as a nephrotic syndrome consequence, has only occasionally been documented. We describe a case of multiloculated pleural effusion that did not react to conventional chest tube drainage but resolved completely and dramatically in response to intrapleural streptokinase.

Shear stimulated red blood cell microparticles: Effect on clot structure, flow and fibrinolysis.

Microparticles (MPs) have activity in thrombus promotion and generation. Erythrocyte microparticles (ErMPs) have been reported to accelerate fibrinolysis in the absence of permeation. We hypothesized that shear induced ErMPs would affect fibrin structure of clots and change flow with implications for fibrinolysis. To determine the effect of ErMPs on clot structure and fibrinolysis. Plasma with elevated ErMPs was isolated from whole blood or from washed red blood cells (RBCs) resuspended in platelet free plasma (PFP) after high shear. Dynamic light scattering (DLS) provided size distribution of ErMPs from sheared samples and unsheared PFP controls. Clots were formed by recalcification for flow/lysis experiments and examined by confocal microscopy and SEM. Flow rates through clots and time-to-lysis were recorded. A cellular automata model showed the effect of ErMPs on fibrin polymerization and clot structure. Coverage of fibrin increased by 41% in clots formed from plasma of sheared RBCs in PFP over controls. Flow rate decreased by 46.7% under a pressure gradient of 10 mmHg/cm with reduction in time to lysis from 5.7 ± 0.7 min to 12.2 ± 1.1 min (p < 0.01). Particle size of ErMPs from sheared samples (200 nm) was comparable to endogenous microparticles. ErMPs alter the fibrin network in a thrombus and affect hydraulic permeability resulting in decelerated delivery of fibrinolytic drugs.

Fibrinolytic drugs induced hemorrhage: mechanisms and solutions.

Thrombosis has been emerging as a major global life-threatening issue with high mortality and serious complications, especially in the post-COVID-19 era. Compared with the commonly used plasminogen activators thrombolytic drugs, fibrinolytic drugs are no longer heavily dependent on the patients' own plasminogen, which are poorly expressed in most patients. As a novel "direct acting" thrombolytic agent, fibrinolytic drugs are considered to have stronger thrombolytic efficacy and safety than the widely used plasminogen activators. However, the risk of their hemorrhage remains a major concern. Herein, the molecular mechanisms and solutions were summarized for the first time based on the systematic review of the latest developments, which could shed new light on the development of novel safety fibrinolytic drugs in the future.

Use of Tenecteplase in Acute Ischemic Stroke in the Time of SARS-CoV-2.

Tenecteplase (TNK) is a fibrinolytic drug that is administrated in a single bolus, recommended in eligible patients with acute ischemic stroke prior to mechanical thrombectomy. This study explores its usefulness in adverse situations, such as the SARS-CoV-2 pandemic. We conducted a retrospective study involving consecutive patients with suspected acute ischemic stroke treated either with intravenous fibrinolysis with alteplase during 2019 or with TNK (.25 mg/kg) between March 2020 and February 2021. A comparative analysis was made to compare patient treatment times and prognosis. A total of 117 patients treated with alteplase and 92 with TNK were included. No significant differences were observed in age, main vascular risk factors or previous treatments. The median National Institutes of Health Stroke Scale was 8 in the alteplase group and 10 in those treated with TNK (P = .13). Combined treatment with mechanical thrombectomy was performed in 47% in the alteplase group and 46.7% in the TNK group; Thrombolysis In Cerebral Infarction scale 2b-3 recanalization was achieved in 83% and 90.7%, respectively (P = .30). There was a decrease in onset-to-needle median time (165min vs 140min, P < .01) and no significant variations in door-needle median time. There was no significant difference in the incidence of symptomatic hemorrhagic transformation in mortality or functional independence at 3months. The easier administration of TNK has improved the accessibility of fibrinolytic therapy, even in adverse circumstances, such as the COVID-19 pandemic. Its use appears to be safe and effective, even in patients who are not candidates for mechanical thrombectomy.

Potensi Ekstrak Kasar Enzim dari Tempe Kedelai Hitam (Glycine soja (L.) Merr.) sebagai Obat Fibrinolitik Alami dengan Metode Clot Lysis In Vitro

Fibrinolytic enzymes are enzymes that can be used to break down fibrin. In thrombus therapy (cardiovascular disease), this enzyme has an activity similar to plasmin, which is able to reduce fibrin by hydrolyzing fibrin into dissolved products and inhibiting the formation of fibrin clots that can trigger cardiovascular disease. Black soybean tempeh has various benefits, one of which is to lower the risk of cardiovascular disease and reduce the risk of blood clots. Due to the content of the enzyme protease in black soybeans which is able to degrade fibrin threads. The purpose of this study is to determine the potential of black soybean tempeh (Glycine soja (L.) Merr) can produce enzyme extracts as natural fibrinolytic drugs. This study was conducted by taking ingredients, crude extraction of enzymes from black soybean tempeh by centrifugation, purification of crude extracts of enzymes using ammonium sulfate salts of 80%, determination of enzyme protein levels with the Lowry method and testing of fibrinolytic potential with the clot lysis method in vitro. The variation in the concentration of the extract used in the test was 12.5; 25; 50 and 100%. The results showed that crude extracts of black soybean tempeh enzymes were able to lyse blood clots. The protein content of the black soybean tempeh extract sample after purification using ammonium sulfate was 245.76 ?g/mL. The optimum percentage of blood clot lysis at a concentration of 100% of the sample after purification was 59%.

Fibrinolytic Therapy in Purulent Pericarditis.

Purulent pericarditis (PP) is rare disease, and if left untreated, it is associated with very high mortality, nearly 100%. A considerable clinical problem due to PP is a very high probability of developing constrictive pericarditis (CP). Pericardial drainage is essential in the treatment of PP and should be performed urgently. The use of broad-spectrum antibiotic therapy is equally important. Unfortunately, fibrin deposits often create occulated spaces and reservoirs that reduce the penetration of antibiotics and their effectiveness. The rationale for the intrapericardial use of fibrinolytic drugs in PP is based on their ability to dissolve fibrin strands and collagen fibres, thus improving the penetration of antibiotics to the pericardial sac and lowering the risk of CP. The choice of the drug, as well as its dosage and the method of administration is still under debate. The authors of the article share their experiences and review current literature on this rare topic.

Activated Platelet‐Targeted IR780 Immunoliposomes for Photothermal Thrombolysis

AbstractAcute thrombosis is a leading cause of mortality and morbidity worldwide. Pharmacological thrombolysis relies on plasminogen activators (PAs), which are associated with major side effects including potentially fatal bleeding. Alternative therapeutic options that do not rely on PAs are urgently required. Here, the efficacy of targeted photothermal therapy is evaluated for thrombolysis using liposomes loaded with IR780 dye, which release heat upon near‐infrared (NIR) irradiation. Liposomes targeted to activated platelets—one of the main components of thrombi—accumulate preferentially in thrombi both in vitro and in vivo compared to non‐targeted controls. In a mouse model of thrombosis, targeted IR780 immunoliposomes (Tar‐IR‐L) produce ≈12 °C average local temperature increase upon NIR irradiation (5 min, 1 W cm−2). This causes a significant reduction in clot area compared to controls treated with non‐targeted liposomes or phosphate‐buffered saline, which only increase local temperature slightly (6 and 3 °C) when irradiated. Co‐loading a low‐dose single chain urokinase plasminogen activator (scuPA) to targeted IR780 liposomes (Tar‐scuPA‐IR‐L) does not result in a superior thrombolytic effect, which indicates that photothermal therapy alone may allow thrombolysis without the need for fibrinolytic drugs. This approach may prevent potential bleeding complications, promising a safer alternative to current pharmacological approaches.

In-hospital major bleeding in patients with acute coronary syndrome medically treated with dual anti-platelet therapy: Associated factors and impact on mortality.

Major bleeding is associated with poor hospital prognosis in patients with acute coronary syndrome (ACS). Despite its clinical importance, there are limited studies on the incidence and risk factors for major bleeding in ACS patients with dual anti-platelet therapy (DAPT) without access to revascularization. We analyzed data from 19,186 patients on DAPT after ACS with no access to revascularization from Clinical Pathway for Acute Coronary Syndrome in China Phase 3 (CPACS-3) cohort, which was conducted from 2011 to 2014. Major bleeding included intracranial hemorrhage, clinically significant bleeding, or bleeding requiring blood transfusion. Factors associated with in-hospital major bleeding were assessed using Poisson regressions with generalized estimating equations to account for the clustering effect. A total of 75 (0.39%) patients experienced major bleeding during hospitalization. Among subtypes of ACS, 0.65% of patients with STEMI, 0.33% with NSTEMI, and 0.13% with unstable angina had in-hospital major bleeding (p < 0.001). The patients who experienced major bleeding had a longer length of stay (median 12 vs. 9 days, p = 0.011) and a higher all-cause in-hospital death rate (22.7 vs. 3.7%, p < 0.001). Multivariable analysis showed advancing age (RR = 1.52 for every 10 years increase, 95% CI: 1.13, 2.05), impaired renal function (RR = 1.79, 95% CI: 1.10, 2.92), use of fibrinolytic drugs (RR = 2.93, 95% CI: 1.55, 5.56), and severe diseases other than cardiovascular and renal diseases (RR = 5.56, 95% CI: 1.10, 28.07) were associated with increased risk of major bleeding, whereas using renin-angiotensin system inhibitors (RR = 0.54, 95% CI: 0.36, 0.81) was associated with decreased risk of major bleeding. These independent factors together showed good predictive accuracy with an AUC of 0.788 (95% CI: 0.734, 0.841). Among ACS patients on DAPT, advancing age, impaired renal function, thrombolytic treatment, and severe comorbidities were independently associated with a higher risk of in-hospital major bleeding.

Infecciones pleurales

Pleural infection is an invasion of the pleural membranes and the space between them by different microorganisms either directly or indirectly. Of note among them are parapneumonic infection and tuberculosis, given their frequency and specific treatments. The imaging test of choice at present is a chest ultrasound, both for the diagnosis and for guiding the thoracentesis, detecting local complications, and providing follow-up. A biochemical and microbiological analysis of the pleural fluid are necessary for confirming the infection, identifying complications, and guiding treatment. Delays in starting antibiotic treatment are related to high morbidity and mortality. Therefore, treatment will be started empirically in most cases. If the pleural effusion is complicated, performing invasive techniques in the pleural cavity should be evaluated. These techniques include the placement of pleural drainage, instillation of fibrinolytic drugs and viscosity-reducing drugs in the pleural space, and surgical treatment if there are septi in the pleural space, an absence of pulmonary re-expansion, or uncontrolled complications of previous treatment. A delay in providing these treatments also increases the disease's morbidity and mortality.

Using real world evidence to generate cost-effectiveness analysis of fibrinolytic therapy in patients with ST-segment elevation myocardial infarction in Thailand

SummaryBackgroundDue to limited access to primary percutaneous coronary intervention for the management of ST-segment elevation myocardial infarction (STEMI) in low-to-middle-income countries (LMICs), fibrinolysis serves as a vital alternative reperfusion therapy. Among fibrinolytic agents, the cost-effectiveness of tenecteplase (TNK) in LMICs as compared to streptokinase (SK) for STEMI management remains unknown.MethodsCost-effectiveness was analyzed using a hybrid model consisting of short-term analysis (30-days decision tree model) and long-term analysis (Markov model). Both health care provider and societal perspectives over a lifetime horizon with 3% discount rate were considered. Input parameters were obtained from Thailand's national health database, a network meta-analysis and literature review. Outcome measure was an incremental cost-effectiveness ratio (ICER) determined by an incremental cost per quality-adjusted life years (QALY) gain. An ICER of less than $5,590 per QALY gain is considered cost-effective. Series of sensitivity analyses were also performed.FindingsFrom the societal perspective, TNK increases cost by $827 and increases QALY by 0·173. Thus, the ICER is $4,777 per QALY gained. Similarly, the ICER from health care provider perspective is $4,664 per QALY gained. In the probabilistic sensitivity analysis, using 5,590 USD per QALY as threshold, the probability of TNK being cost-effective was 83% from both perspectives. The most influential parameters were risk ratio of death for treatment with TNK compared to SK and drug cost of TNK.InterpretationIn a resource-limited country like Thailand, tenecteplase is a cost-effective fibrinolytic drug for treatment of STEMI compared to streptokinase.FundingNone.