-
Experimental & Molecular Medicine Mar 2020The function of the fibrinolytic system was first identified to dissolve fibrin to maintain vascular patency. Connections between the fibrinolytic system and many other... (Review)
Review
The function of the fibrinolytic system was first identified to dissolve fibrin to maintain vascular patency. Connections between the fibrinolytic system and many other physiological and pathological processes have been well established. Dysregulation of the fibrinolytic system is closely associated with multiple pathological conditions, including thrombosis, inflammation, cancer progression, and neuropathies. Thus, molecules in the fibrinolytic system are potent therapeutic and diagnostic targets. This review summarizes the currently used agents targeting this system and the development of novel therapeutic strategies in experimental studies. Future directions for the development of modulators of the fibrinolytic system are also discussed.
Topics: Animals; Antifibrinolytic Agents; Fibrin; Fibrinolysis; Humans; Inflammation; Neoplasms; Thrombosis
PubMed: 32152451
DOI: 10.1038/s12276-020-0397-x -
Medicine Mar 2016Educational advice is often given to patients starting treatment with vitamin K Antagonists (VKAs). A great emphasis is made on nutritional information. Common belief is... (Meta-Analysis)
Meta-Analysis
Educational advice is often given to patients starting treatment with vitamin K Antagonists (VKAs). A great emphasis is made on nutritional information. Common belief is that dietary vitamin K intake could counteract the anticoagulant effect by VKAs and for many years, patients have been discouraged to consume vitamin-K-rich foods, such as green leafy vegetables.The objective of this study is to summarize the current evidence supporting the putative interaction between dietary vitamin K intake and changes in INR with the VKAs.Data sources are MEDLINE via PubMed and Cochrane database.All clinical studies investigating the relationship between dietary vitamin K and measures of anticoagulation were included. We excluded all studies of supplementation of vitamin K alone.We performed a systematic review of the literature up to October 2015, searching for a combination of "food," "diet," "vitamin K," "phylloquinone," "warfarin," "INR," "coagulation," and "anticoagulant."Two dietary interventional trials and 9 observational studies were included. We found conflicting evidence on the effect of dietary intake of vitamin K on coagulation response. Some studies found a negative correlation between vitamin K intake and INR changes, while others suggested that a minimum amount of vitamin K is required to maintain an adequate anticoagulation. Median dietary intake of vitamin K1 ranged from 76 to 217 μg/day among studies, and an effect on coagulation may be detected only for high amount of vitamin intake (>150 μg/day).Most studies included patients with various indications for VKAs therapy, such as atrial fibrillation, prosthetic heart valves, and venous thromboembolism. Thus, INR target was dishomogeneous and no subanalyses for specific populations or different anticoagulants were conducted. Measures used to evaluate anticoagulation stability were variable.The available evidence does not support current advice to modify dietary habits when starting therapy with VKAs. Restriction of dietary vitamin K intake does not seem to be a valid strategy to improve anticoagulation quality with VKAs. It would be, perhaps, more relevant to maintain stable dietary habit, avoiding wide changes in the intake of vitamin K.
Topics: Antifibrinolytic Agents; Blood Coagulation; Dietary Supplements; Humans; International Normalized Ratio; Nutritional Requirements; Thromboembolism; Vitamin K
PubMed: 26962786
DOI: 10.1097/MD.0000000000002895 -
Pediatric Neurology Dec 2020
Topics: Antifibrinolytic Agents; Child Abuse; Humans; Infant, Newborn; Physician's Role; Treatment Refusal; Vitamin K
PubMed: 33190689
DOI: 10.1016/j.pediatrneurol.2020.09.006 -
American Journal of Physiology. Lung... May 2018Pulmonary hypertension (PH) is a progressive and often fatal illness presenting with nonspecific symptoms of dyspnea, lower extremity edema, and exercise intolerance.... (Review)
Review
Pulmonary hypertension (PH) is a progressive and often fatal illness presenting with nonspecific symptoms of dyspnea, lower extremity edema, and exercise intolerance. Pathologically, endothelial dysfunction leads to abnormal intimal and smooth muscle proliferation along with reduced apoptosis, resulting in increased pulmonary vascular resistance and elevated pulmonary pressures. PH is subdivided into five World Health Organization groups based on the disease pathology and specific cause. While there are Food and Drug Administration-approved medications for the treatment of pulmonary arterial hypertension (PAH; Group 1 PH), as well as for chronic thromboembolic PH (Group 4 PH), the morbidity and mortality remain high. Moreover, there are no approved therapies for other forms of PH (Groups 2, 3, and 5) at present. New research has identified molecular targets that mediate vasodilation, anti-inflammatory, and antifibrotic changes within the pulmonary vasculature. Given that PAH is the most commonly studied form of PH worldwide and because recent studies have led to better mechanistic understanding of this devastating disease, in this review we attempt to provide an updated overview of new therapeutic approaches under investigation for the treatment of PH, with a particular focus on PAH, as well as to offer guidelines for future investigations.
Topics: Animals; Anti-Inflammatory Agents; Antifibrinolytic Agents; Humans; Hypertension, Pulmonary; Vasodilator Agents
PubMed: 29388467
DOI: 10.1152/ajplung.00259.2017 -
Anaesthesia Mar 2023
Topics: Humans; Tranexamic Acid; Arthroplasty, Replacement, Knee; Antifibrinolytic Agents; Postoperative Hemorrhage; Blood Loss, Surgical
PubMed: 36599643
DOI: 10.1111/anae.15960 -
Annals of Neurology Jan 2016Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used... (Review)
Review
Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in-hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid-associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid-associated seizures and by translating scientific findings into therapeutic interventions for patients.
Topics: Animals; Antifibrinolytic Agents; Humans; Seizures; Tranexamic Acid
PubMed: 26580862
DOI: 10.1002/ana.24558 -
American Journal of Hematology Sep 1997Although excessive bleeding is widely recognized as a common complication of cardiac surgery, the recent success of antifibrinolytic drugs as prophylactic hemostatic... (Review)
Review
Although excessive bleeding is widely recognized as a common complication of cardiac surgery, the recent success of antifibrinolytic drugs as prophylactic hemostatic agents has received little attention outside the surgical literature. The etiology of the coagulopathy following cardiac surgery is clearly multifactorial; however, the success of antifibrinolytic drugs as hemostatic agents suggests that fibrinolysis contributes to bleeding in this setting. Increasingly widespread administration of these drugs necessitates increased awareness of the risks and benefits posed by perioperative antifibrinolytic therapy. The objectives of this review are to understand the mechanisms of action of antifibrinolytic drugs in the context of the normal hemostatic response and to review evidence pertaining to the efficacy and safety of antifibrinolytic drugs as hemostatic agents during cardiac surgery.
Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Cardiac Surgical Procedures; Hemostasis; Humans
PubMed: 9298865
DOI: 10.1002/(sici)1096-8652(199709)56:1<32::aid-ajh7>3.0.co;2-3 -
European Journal of Trauma and... Jun 2016Severe trauma and massive haemorrhage represent the leading cause of death and disability in patients under the age of 45 years in the developed world. Even though much... (Review)
Review
Severe trauma and massive haemorrhage represent the leading cause of death and disability in patients under the age of 45 years in the developed world. Even though much advancement has been made in our understanding of the pathophysiology and management of trauma, outcomes from massive haemorrhage remain poor. This can be partially explained by the development of coagulopathy, acidosis and hypothermia, a pathological process collectively known as the "lethal triad" of trauma. A number of pharmacological adjuncts have been utilised to stop bleeding, with a wide variation in the safety and efficacy profiles. Antifibrinolytic agents in particular, act by inhibiting the conversion of plasminogen to plasmin, therefore decreasing the degree of fibrinolysis. Tranexamic acid, the most commonly used antifibrinolytic agent, has been successfully incorporated into most trauma management protocols effectively reducing mortality and morbidity following trauma. In this review, we discuss the current literature with regard to the management of haemorrhage following trauma, with a special reference to the use of pharmacological adjuncts. Novel insights, concepts and treatment modalities are also discussed.
Topics: Acidosis; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Transfusion; Clinical Protocols; Fibrinolysis; Hemorrhage; Humans; Hypothermia; Multiple Trauma; Tranexamic Acid
PubMed: 26660675
DOI: 10.1007/s00068-015-0613-x -
The Cochrane Database of Systematic... Nov 2016Haemoptysis is a common pathology around the world, occurring with more frequency in low-income countries. It has different etiologies, many of which have infectious... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Haemoptysis is a common pathology around the world, occurring with more frequency in low-income countries. It has different etiologies, many of which have infectious characteristics. Antifibrinolytic agents are commonly used to manage bleeding from different sources, but their usefulness in pulmonology is unclear.
OBJECTIVES
To evaluate the effectiveness and safety of antifibrinolytic agents in reducing the volume and duration of haemoptysis in adult and paediatric patients.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library, EMBASE and LILACS for publications that describe randomized controlled trials (RCTs) of antifibrinolytic therapy in patients presenting with haemoptysis. We also performed an independent search in MEDLINE for relevant trials not yet included in CENTRAL or DARE. Searches are up to date to the 19th September 2016. We conducted electronic and manual searches of relevant national and international journals. We reviewed the reference lists of included studies to locate relevant randomized controlled trials (RCTs). An additional search was carried out to find unpublished RCTs.
SELECTION CRITERIA
We included RCTs designed to evaluate the effectiveness and safety of antifibrinolytic agents in reducing haemoptysis in adult and paediatric patients of both genders presenting with haemoptysis of any etiology and severity. The intervention of interest was the administration of antifibrinolytic agents compared with placebo or no treatment.
DATA COLLECTION AND ANALYSIS
All reviewers independently assessed methodological quality and extracted data tables pre-designed for this review.
MAIN RESULTS
The electronic literature search identified 1 original study that met the eligibility criteria. One unpublished study was also identified through manual searches. Therefore two randomized controlled trials met the inclusion criteria: Tscheikuna 2002 (via electronic searches) and Ruiz 1994 (via manual searches). Tscheikuna 2002, a double-blind RCT performed in Thailand, evaluated the effectiveness of tranexamic acid (TXA, an antifibrinolytic agent) administered orally in 46 hospital in- and outpatients with haemoptysis of various etiologies. Ruiz 1994, a double-blind RCT performed in Peru, evaluated the effectiveness of intravenous TXA in 24 hospitalised patients presenting with haemoptysis secondary to tuberculosis.Pooled together, results demonstrated a significant reduction in bleeding time between patients receiving TXA and patients receiving placebo with a weighted mean difference (WMD) of -19.47 (95% CI -26.90 to -12.03 hours), but with high heterogeneity (I² = 52%). TXA did not affect remission of haemoptysis evaluated at seven days after the start of treatment. Adverse effects caused by the drug's mechanism of action were not reported. There was no significant difference in the incidence of mild side effects between active and placebo groups (OR 3.13, 95% CI 0.80 to 12.24).
AUTHORS' CONCLUSIONS
There is insufficient evidence to judge whether antifibrinolytics should be used to treat haemoptysis from any cause, though limited evidence suggests they may reduce the duration of bleeding.
Topics: Administration, Oral; Adult; Antifibrinolytic Agents; Hemoptysis; Humans; Injections, Intravenous; Peru; Randomized Controlled Trials as Topic; Thailand; Tranexamic Acid; Tuberculosis, Pulmonary
PubMed: 27806184
DOI: 10.1002/14651858.CD008711.pub3 -
British Journal of Anaesthesia Oct 2013Antifibrinolytic drugs have become almost ubiquitous in their use during major surgery when bleeding is expected or commonplace. Inhibition of the fibrinolytic pathway... (Review)
Review
Antifibrinolytic drugs have become almost ubiquitous in their use during major surgery when bleeding is expected or commonplace. Inhibition of the fibrinolytic pathway after tissue injury has been consistently shown to reduce postoperative or traumatic bleeding. There is also some evidence for a reduction of perioperative blood transfusion. However, evidence of complications associated with exaggerated thrombosis also exists, although this appears to be influenced by the choice of the individual agent and the dose administered. There is controversy over the use of the serine protease inhibitor aprotinin, whose license was recently withdrawn but may shortly become available on the market again. In the UK, tranexamic acid, a tissue plasminogen and plasmin inhibitor, is most commonly used, with evidence for benefit in cardiac, orthopaedic, urological, gynaecological, and obstetric surgery. In the USA, ε-aminocaproic acid, which also inhibits plasmin, is commonly used. We have reviewed the current literature for this increasingly popular class of drugs to support clinical judgement in daily anaesthetic practice.
Topics: Aminocaproic Acid; Antifibrinolytic Agents; Aprotinin; Blood Loss, Surgical; Cardiac Surgical Procedures; Female; Hemorrhage; Humans; Liver; Neurosurgical Procedures; Orthopedic Procedures; Postoperative Hemorrhage; Postpartum Hemorrhage; Pregnancy; Tranexamic Acid; Wounds and Injuries
PubMed: 23661406
DOI: 10.1093/bja/aet154