Amounts of tranexamic acid in breastmilk appear to be low. Recent expert opinion considers that breastfeeding should be permitted in infants whose mothers require treatment with tranexamic acid.[1,2] Tranexamic acid is used for hereditary angioedema in low-income countries where first-line treatments are not available, but should not be used if C1-INH is available.[3]

To compare the efficacy and safety of different doses of intravenous thrombolytic agents in patients with acute ischemic stroke (AIS) and guide optimal dose selection. We searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL until March 2025 to identify randomized controlled trials (RCTs) evaluating alteplase (tPA), tenecteplase (TNK), reteplase, and recombinant human prourokinase (rhPro-UK) at any dose in patients with AIS. Analysis was performed using R software, and risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. Primary outcomes included symptomatic intracranial hemorrhage (sICH), 90-day mortality, excellent functional outcome (defined as modified Rankin Scale [mRS] score 0-1), and functional independence (defined as mRS 0-2). We included 21 RCTs (16,643 patients). Compared to tPA (0.9 mg/kg), tPA (0.6 mg/kg) was associated with a significantly lower risk of sICH (RR = 0.48, 95% CI: 0.27-0.86), while TNK (0.4 mg/kg) showed a higher risk (RR = 1.88, 95% CI: 1.06-3.35). No significant differences were observed in 90-day mortality, functional independence, or serious adverse events across interventions. Reteplase (18 + 18 mg) (RR = 1.13, 95% CI: 1.05-1.21) and TNK (0.25 mg/kg) (RR = 1.05, 95% CI: 1.01-1.10) significantly improved 90-day excellent functional recovery compared to tPA (0.9 mg/kg). TNK (0.32 mg/kg) showed the lowest risk probability for any ICH and parenchymal hemorrhage. Some safety outcomes showed dose-dependent effects: lower-dose tPA and intermediate-dose TNK reduced ICH risk compared to higher doses, while mortality and functional independence remained comparable across doses.

A total number of 20 cases of prosthetic valve thrombosis (PVT) involving left-sided bileaflet St Jude's prosthesis (16), Medtronic Hall (3), and pulmonary prosthesis (1) are reported. Streptokinase (STK) fibrinolysis provided excellent results in 66.6% of cases with thrombosed St Jude's mitral prosthesis and remains the preferred option for this subset. Percutaneous manipulation of the mitral disk proved a useful adjuvant. Reteplase produced gratifying results in pulmonary mechanical prosthesis. However, thrombosed aortic prosthesis responded unfavorably to fibrinolysis. About six patients who failed to respond to thrombolysis had excellent results with valve replacement surgery. Two patients (10%) succumbed due to extremely high-risk clinical characteristics.

Fibrinolytic therapy plays a pivotal role in the management of thromboembolic diseases by promoting plasmin-mediated fibrin degradation and vessel recanalization, which frequently comes at the cost of increased risk of hemorrhagic events, including intracranial bleeding. Since the discovery of streptokinase in 1933, several additional fibrinolytic agents have been developed. Two plasminogen activators-urokinase and tissue plasminogen activator (tPA)-were identified in human samples. Through recombinant DNA technology, tPA was cloned and modified to produce alteplase. Subsequent efforts to prolong its plasma half-life led to the development of mutant derivatives such as tenecteplase and reteplase. Although fibrinolytic therapy in patients with ST-segment elevation myocardial infarction is currently restricted to those who cannot undergo primary percutaneous coronary intervention within 120 minutes of presentation, it has been a mainstay treatment for acute ischemic stroke and pulmonary embolism (PE) with hemodynamic compromise. Catheter-directed fibrinolysis has been evaluated in patients with intermediate-risk PE, deep vein thrombosis, acute limb ischemia, and after endovascular thrombectomy for ischemic stroke. Fibrinolytic agents have also been used in other clinically important indications, such as central venous access device thrombosis, mechanical prosthetic valve thrombosis, left ventricular assist device thrombosis, central retinal artery occlusion, cerebral venous sinus thrombosis, and left ventricular thrombus. This paper provides a comprehensive overview of the current applications, approved indications, evolving roles, and future directions of fibrinolytic agents in thromboembolic diseases.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are key initiating events in the development of venous thromboembolism (VTE), a condition associated with significant morbidity, mortality, and long-term complications. While traditional therapies have focused on anticoagulation and thrombolysis, current evidence describes the pivotal role of immune pathways in the pathogenesis and progression of thrombosis. This review explores the multifaceted mechanisms underlying DVT and PE, emphasizing the contribution of inflammation, leukocyte activation, and immuno-thrombosis to thrombus formation and embolization. Key immune players such as neutrophil extracellular traps (NETs), inflammasomes, antibodies, and the STING pathway act in concert with coagulation cascades, highlighting potential targets for therapeutic modulation. We critically evaluated and discussed the efficacy and risks associated with thrombolytic agents such as alteplase, reteplase, and tenecteplase, particularly in severe or hemodynamically unstable cases. In addition, we reviewed new and innovative approaches including immune-targeted therapies and nanoparticle-based drug delivery systems, which provide the promise of more precise, safer, and cost-effective interventions. By integrating immunologic insights with evolving thrombolytic strategies, this paper supports a more tailored approach to managing DVT and PE, with the goal of reducing recurrence, minimizing complications, and enhancing long-term patient outcomes.

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are among the most widespread drugs for the prevention of cardiovascular mortality and morbidity. Nevertheless, they are known to cause bradykinin (BK)-mediated angioedema (AE), a paroxysmal, localized, self-limiting, and potentially fatal swelling of the subcutaneous and/or submucosal tissue, due to a temporary increase in vascular permeability. Unlike hereditary angioedema (HAE), which can be mediated similarly by BK, no diagnostic tools, guidelines, or drugs have yet been approved for the diagnosis and treatment of acute non-allergic drug-induced AE. Besides ACEIs and ARBs, inhibitors of dipeptidyl peptidase-IV, neprilysin inhibitors, and tissue plasminogen activators are known to cause AE as an adverse effect. Currently, there are insufficient data on the prevention of AE caused by pharmacological therapies. In addition, the molecular mechanisms underlying BK-mediated AE caused by drugs, which are discussed here, are not fully explained. Specific approved drugs and a structured diagnostic workflow are unmet needs and are required for the management of this kind of AE. The aim of this review is to provide physicians with accurate knowledge of potentially life-threatening drug reactions so that they can be better understood and managed.

Intravenous thrombolysis is one of the standard treatments of acute ischemic stroke. Over the last decades, alteplase (recombinant tissue type plasminogen activator, rt-PA) has been established as the main thrombolytic agent worldwide. However, the short plasma half-life of rt-PA poses logistical challenges, as it necessitates administration as a 10 % bolus followed by a 90 % infusion over one hour. These logistical difficulties, combined with the search for agents with improved efficacy and safety profiles, have spurred the development of alternative thrombolytic agents. This review summarizes current clinical evidence and emerging research on novel thrombolytic agents in acute ischemic stroke, including tenecteplase, reteplase, desmoteplase, urokinase, staphylokinase, JX10, LT3100, Ancrod, and TS23. Among these agents, tenecteplase has been most extensively studied and is already recommended for selected indications by the European Stroke Organization (ESO) and the American Heart Association and American Stroke Association (AHA/ASA). Other agents are still undergoing early clinical investigation and show different levels of potential in terms of effectiveness, safety, and ease of administration.

Acute ischemic stroke leads to rapid and progressive neuronal losses. Early revascularization with thrombolytics and/or endovascular thrombectomy plays an important role in salvaging brain infarction. Currently, alteplase and tenecteplase are approved thrombolytics for the treatment of acute ischemic stroke, whereas favorable outcomes of reteplase have recently been reported in a phase 3 clinical trial. These thrombolytics share common and distinct pharmacological characteristics, which contribute to their efficacy and safety in patients. In this review, biological profiles of alteplase, tenecteplase, and reteplase, including their advantages versus disadvantages in acute ischemic stroke, are discussed. Tenecteplase has high fibrin specificity, increased resistance to plasminogen activator inhibitor-1 (PAI-1), wider concentration-response curve, and less off-target activities, which support its efficacy with low incidence of symptomatic intracranial hemorrhage (sICH). Reteplase greatly penetrates into the clot with prolonged retention, generating durable clot lysis. This activity might be associated with its excellent clinical outcomes in patients, although reteplase is sensitive to PAI-1. Notably, reteplase and alteplase produce off-target activities by inducing hypofibrinogenemia and hypoplasminogenemia, which may increase risk of hemorrhagic transformation. Moreover, orolingual angioedema is a life-threatening complication of all thrombolytics. Mechanistically, an increase in plasmin by thrombolytics leads to bradykinin generation. In addition, plasmin activates mast cell degranulation (e.g., histamine release). Together, these biopharmacological data of thrombolytics promote insights into their clinical outcomes, and might provide comprehensive bases for future research.

Thrombolytic therapy is a cornerstone in managing acute ischaemic stroke, marking significant advancements in treatment. Various generations of thrombolytics play crucial roles in different strategies, including intravenous thrombolysis, bridging therapy and thrombolysis beyond the conventional time window. The continuous development of thrombolytics has brought notable improvements. Compared to first-generation urokinase, second-generation alteplase and third-generation tenecteplase offer significant pharmacological advantages, such as enhanced fibrin specificity and longer half-lives. Tenecteplase demonstrates non-inferiority to alteplase regarding efficacy and safety, with the added benefit of a more convenient administration method. Ongoing trials continue to reveal additional evidence. Furthermore, other thrombolytic agents, including reteplase and non-immunogenic recombinant staphylokinase, are gaining increasing interest in the medical community. This review examines the structural characteristics, pharmacological properties, efficacy and safety profiles of these thrombolytic drugs. It also provides a detailed analysis of the performance of thrombolytic therapy in different acute ischaemic stroke patient subgroups, aiming to trace the evolution of these treatments and compare their effectiveness in acute ischaemic stroke. The goal is to offer a scientific basis for clinical practices and future development of thrombolytic therapies.