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Scandinavian Journal of Gastroenterology Mar 1983The mucosal fibrinolytic activity was estimated in 14 patients with duodenal ulcer before and after 4 weeks' treatment with cimetidine. A significant reduction in...
The mucosal fibrinolytic activity was estimated in 14 patients with duodenal ulcer before and after 4 weeks' treatment with cimetidine. A significant reduction in fibrinolytic activity in the corpus and antrum mucosa was found after treatment. In patients with healed ulcer after treatment, the activity was lower than in patients with unhealed ulcers, but no significance was proved. Similarly, in five patients with gastric ulcer, reduction in fibrinolytic activity was found after cimetidine treatment but in the corpus mucosa only. The fibrinolytic activity in the mucosa is caused by plasmin. Whether this antifibrinolytic property of cimetidine is of any importance in the treatment of ulcer disease is still unknown.
Topics: Adult; Aged; Antifibrinolytic Agents; Cimetidine; Duodenal Ulcer; Female; Fibrinolysis; Humans; Intestinal Mucosa; Male; Middle Aged
PubMed: 6673059
DOI: 10.3109/00365528309181600 -
Journal of Thrombosis and Haemostasis :... Mar 2024Tranexamic acid (TXA) is an antifibrinolytic agent originally developed for the management of bleeding in the setting of postpartum hemorrhage (PPH). Over the last 15... (Review)
Review
Tranexamic acid (TXA) is an antifibrinolytic agent originally developed for the management of bleeding in the setting of postpartum hemorrhage (PPH). Over the last 15 years, there has been accumulating evidence on the use of TXA for the treatment of active bleeding in a variety of clinical contexts. Clinical trials have shown that the efficacy and safety of TXA for the treatment of bleeding differ according to the clinical context in which it is being administered, timing of administration, and dose. Early administration is important for efficacy, particularly in trauma and PPH. Further studies are needed to understand the mechanisms by which TXA provides benefit, optimal modes of administration and dosing, and its effect in some clinical settings, such as spontaneous intracerebral hemorrhage. There is no evidence that TXA increases the risk of thrombotic events in patients with major bleeding overall. However, there is evidence of increased risk of venous thrombosis in patients with gastrointestinal bleeding. There is also evidence of increased risk of seizures with the use of higher doses. This review summarizes the current evidence for the use of TXA for patients with active bleeding and highlights the importance of generating evidence of efficacy and safety of hemostatic interventions specific to the bleeding contexts-as findings from 1 clinical setting may not be generalizable to other contexts-and that of individual patient assessment for bleeding, thrombotic, and other risks, as well as important logistical and other practical considerations, to optimize care and outcomes in these settings.
Topics: Pregnancy; Female; Humans; Tranexamic Acid; Antifibrinolytic Agents; Postpartum Hemorrhage; Thrombosis; Gastrointestinal Hemorrhage
PubMed: 37827378
DOI: 10.1016/j.jtha.2023.10.001 -
Nordisk Medicin Feb 1970
Review
Topics: Antifibrinolytic Agents; Chemical Phenomena; Chemistry; Cyclohexanecarboxylic Acids; Fibrinolysis; Humans; Injections, Intravenous
PubMed: 4910677
DOI: No ID Found -
Neurocritical Care 2008In the current era of early surgery, there has been little interest in the use of antifibrinolytic therapy to prevent rebleeding after aneurysmal subarachnoid hemorrhage... (Review)
Review
In the current era of early surgery, there has been little interest in the use of antifibrinolytic therapy to prevent rebleeding after aneurysmal subarachnoid hemorrhage (aSAH). Older studies demonstrated that antifibrinolytics can reduce rebleeding, but long-term therapy results in increased cerebral ischemia from vasospasm, leading to no appreciable effect on mortality. While early surgery would seem to obviate the need for long-term antifibrinolytic use, a subgroup of patients may benefit from early therapy. The rate of pre-operative rebleeding may be as high as 9-17%, causing significant morbidity and mortality. Short-term use of antifibrinolytic agents (less than 3 days) in the presence of calcium channel blocking therapy has shown promising results. A randomized clinical trial of early antifibrinolytic therapy conducted in 2002 showed a significant decrease in rebleeding and a non-significant decrease in overall mortality. In this review, we examine the clinical pharmacology, dosing, monitoring, complications, and side effects of antifibrinolytic treatment. We conclude that early short-term antifibrinolytic therapy might be a reasonable strategy to prevent acute rebleeding and improve long-term outcome in aSAH patients. Additional randomized clinical trials are necessary to determine whether this management strategy is effective.
Topics: Antifibrinolytic Agents; Humans; Randomized Controlled Trials as Topic; Secondary Prevention; Subarachnoid Hemorrhage
PubMed: 18386187
DOI: 10.1007/s12028-008-9088-5 -
Seminars in Hematology Jan 2004Factor XI (FXI) deficiency leads to an injury-related bleeding diathesis, which is notable for the variability in the bleeding tendency and the lack of a clear... (Review)
Review
Factor XI (FXI) deficiency leads to an injury-related bleeding diathesis, which is notable for the variability in the bleeding tendency and the lack of a clear relationship between bleeding and FXI coagulant activity. Bleeding in this disorder occurs especially in areas of high fibrinolytic activity. Although a rare disorder, the frequency of FXI deficiency is high in certain populations, notably persons of Ashkenazi descent and the Basque population of Southern France. In these populations, five mutations of the FXI gene have been identified and a founder effect has been confirmed for three of these. This paper reviews the role of FXI in coagulation and documents factors known to modify the bleeding tendency. Treatment of surgical bleeding in patients with FXI deficiency is reviewed with emphasis on the combined use of recombinant activated factor VII (rFVIIa; NovoSeven(R), Novo Nordisk, Bagsvaerd, Denmark) and the antifibrinolytic agent, tranexamic acid.
Topics: Antifibrinolytic Agents; Blood Coagulation Factors; Factor VII; Factor VIIa; Factor XI Deficiency; Female; Fibrinolysis; Hemophilia A; Hemorrhage; Humans; Male; Recombinant Proteins; von Willebrand Diseases
PubMed: 14872426
DOI: 10.1053/j.seminhematol.2003.11.015 -
JAMA Feb 1965
Topics: Aminocaproates; Aminocaproic Acid; Antifibrinolytic Agents; Humans; Toxicology
PubMed: 14238032
DOI: No ID Found -
Journal of Pediatric Hematology/oncology Apr 2022Children and adolescents undergoing posterior spinal fusion for scoliosis experience high rates of bleeding and blood product transfusion. Antifibrinolytic therapy is... (Review)
Review
Children and adolescents undergoing posterior spinal fusion for scoliosis experience high rates of bleeding and blood product transfusion. Antifibrinolytic therapy is one key strategy to decrease blood loss and transfusion in pediatric scoliosis surgery. Here we review 172 pediatric scoliosis patients (birth to 21 y) who underwent posterior spinal fusion at our institution from 2017 to 2018. We reported rates of blood loss and transfusion, compared patients receiving tranexamic acid to a ε-aminocaproic acid, and evaluated antifibrinolytic agent and laboratory parameters as predictors of blood loss and transfusion. Intraoperatively, 62% received tranexamic acid and 38% received ε-aminocaproic acid. Overall, blood loss (mean intraoperative estimated blood loss=14.9±9.7 mL/kg, 22% with clinically significant blood loss [>20 mL/kg], and mean calculated hemoglobin mass loss=175.9±70.1 g) and transfusion rates (15% with intraoperative allogeneic red blood cell transfusion and mean intraoperative allogeneic red blood cell transfusion volume=12.5±7.1 mL/kg) were similar to previous cohorts studying intraoperative antifibrinolytics. There was no difference in intraoperative estimated blood loss, clinically significant blood loss, calculated hemoglobin mass loss, or transfusion rates between the antifibrinolytic groups. Antifibrinolytic choice was not predictive of blood loss or transfusion. Routine hematologic laboratory parameters and antifibrinolytic choice were insufficient to predict blood loss or other outcomes. Future prospective laboratory-based studies may provide a more comprehensive model of surgical-induced coagulopathy in scoliosis surgery and provide a better tool for predicting blood loss and improving outcomes.
Topics: Adolescent; Aminocaproic Acid; Antifibrinolytic Agents; Blood Loss, Surgical; Child; Humans; Retrospective Studies; Scoliosis; Tranexamic Acid; Treatment Outcome
PubMed: 34654764
DOI: 10.1097/MPH.0000000000002351 -
The Cochrane Database of Systematic... Oct 2023Percutaneous nephrolithotomy (PCNL) is the gold standard for the treatment of large kidney stones but comes with an increased risk of bleeding compared to other... (Review)
Review
BACKGROUND
Percutaneous nephrolithotomy (PCNL) is the gold standard for the treatment of large kidney stones but comes with an increased risk of bleeding compared to other treatments, such as ureteroscopy and shock wave lithotripsy. Tranexamic acid (TXA) is an antifibrinolytic agent that has been used to reduce bleeding complications in other settings.
OBJECTIVES
To assess the effects of TXA in individuals with kidney stones undergoing PCNL.
SEARCH METHODS
We performed a comprehensive literature search of the Cochrane Library, PubMed (including MEDLINE), Embase, Scopus, Global Index Medicus, trials registries, other sources of the grey literature, and conference proceedings. We applied no restrictions on the language of publication nor publication status. The latest search date was 11 May 2023.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that compared treatment with PCNL with administration of TXA to placebo (or no TXA) for patients ≥ 18 years old.
DATA COLLECTION AND ANALYSIS
Two review authors independently classified studies and abstracted data. Primary outcomes were: blood transfusion, stone-free rate (SFR), and thromboembolic events (TEEs). Secondary outcomes were: adverse events (AEs), secondary interventions, major surgical complications, minor surgical complications, unplanned hospitalizations or readmissions, and hospital length of stay (LOS). We performed statistical analyzes using a random-effects model. We rated the certainty of evidence (CoE) according to the GRADE approach using a minimally contextualized approach with predefined thresholds for minimally clinically important differences (MCIDs).
MAIN RESULTS
We analyzed 10 RCTs assessing the effect of systemic TXA in PCNL versus placebo (or no TXA) with 1883 randomized participants. Eight studies were published as full text. One was published in abstract proceedings, but it was separated into two separate studies for the purpose of our analyzes. Average stone surface area ranged 3.45 to 6.62 cm. We also found a single RCT published in full text assessing the effects of topical TXA in PCNL versus placebo (or no TXA) with 400 randomized participants, the results of which are further described in the review. Here we focus only on the results of TXA used systemically. Blood transfusion - Based on a representative baseline risk of 5.7% for blood transfusions taken from a large presentative observational studies, systemic TXA may reduce blood transfusions (risk ratio (RR) 0.45, 95% confidence interval (CI) 0.27 to 0.76; I = 28%; 9 studies, 1353 participants; low CoE). We assumed an MCID of ≥ 2%. Based on 57 participants per 1000 with placebo (or no TXA) being transfused, this corresponds to 31 fewer (from 42 fewer to 14 fewer) participants being transfused per 1000. Stone-free rate - Based on a representative baseline risk of 75.7% for SFR, systemic TXA may increase SFRs (RR 1.11, 95% CI 0.98 to 1.27; I = 62%; 4 studies, 603 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 757 participants per 1000 being stone free with placebo (or no TXA), this corresponds to 83 more (from 15 fewer to 204 more) stone-free participants per 1000. Thromboembolic events - There is probably no difference in TEEs (risk difference (RD) 0.00, 95% CI -0.01 to 0.01; I = 0%; 6 studies, 841 participants; moderate CoE). We assumed an MCID of ≥ 2%. Since there were no thromboembolic events in intervention and/or control groups in 5 out of6 studies, we opted to assess a risk difference with systemic TXA for this outcome. Adverse events - Systemic TXA may increase AEs (RR 5.22, 95% CI 0.52 to 52.72; I = 75%; 4 studies, 602 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 23 participants per 1000 with placebo (or no TXA) having an adverse event, this corresponds to 98 more (from 11 fewer to 1000 more) participants with adverse events per 1000. Secondary interventions - Systemic TXA may have little to no effect on secondary interventions (RR 1.15, 95% CI 0.84 to 1.57; I = 0%; 2 studies, 319 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 278 participants per 1000 with placebo (or no TXA) having a secondary intervention, this corresponds to 42 more (from 44 fewer to 158 more) participants with secondary interventions per 1000. Major surgical complications - Based on a representative baseline risk for major surgical complications of 4.1%, systemic TXA may reduce major surgical complications (RR 0.36, 95% CI 0.21 to 0.62; I = 0%; 5 studies, 733 participants; moderate CoE). We assumed an MCID of ≥ 2%. Based on 41 participants per 1000 with placebo (or no TXA) having a major surgical complication, this corresponds to 26 fewer (from 32 fewer to 16 fewer) participants with major surgical complications per 1000. Minor surgical complications - Systemic TXA may reduce minor surgical complications (RR 0.71, 95% CI 0.45 to 1.10; I = 76%; 5 studies, 733 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 396 participants per 1000 with placebo (or no TXA) having a minor surgical complication, this corresponds to 115 fewer (from 218 fewer to 40 more) participants with minor surgical complications per 1000. Unplanned hospitalizations or readmissions - We are very uncertain how unplanned hospitalizations or readmissions are affected (RR 1.55, 95% CI 0.45 to 5.31; I = not applicable; 1 study, 189 participants; very low CoE). We assumed an MCID of ≥ 2%. Hospital length of stay - Systemic TXA may reduce hospital LOS (mean difference 0.52 days lower, 95% CI 0.93 lower to 0.11 lower; I = 98%; 7 studies, 1151 participants; low CoE). We assumed an MCID of ≥ 0.5 days.
AUTHORS' CONCLUSIONS
Based on 10 RCTs with substantial methodological limitations that lowered all CoE of effect, we found that systemic TXA in PCNL may reduce blood transfusions, major and minor surgical complications, and hospital LOS, as well as improve SFRs; however, it may increase AEs. We are uncertain about the effects of systemic TXA on other outcomes. Findings of this review should assist urologists and their patients in making informed decisions about the use of TXA in the setting of PCNL.
Topics: Humans; Adolescent; Tranexamic Acid; Nephrolithotomy, Percutaneous; Kidney Calculi; Antifibrinolytic Agents; Hemostatics
PubMed: 37882229
DOI: 10.1002/14651858.CD015122.pub2 -
Neurocritical Care Oct 2018A warning leak is a curious phenomenon attributed to cerebral aneurysms. Once the leak occurs, it has been postulated it could lead to a more catastrophic rebleeding.... (Review)
Review
A warning leak is a curious phenomenon attributed to cerebral aneurysms. Once the leak occurs, it has been postulated it could lead to a more catastrophic rebleeding. The designation "warning leak" trickled into neurosurgery vocabulary as early as the 1950s. The phenomenon has been poorly understood and characterized, but its presence spurs emergency physicians and neurointensivists to take action to secure the aneurysm. Rapid treatment of a recently discovered aneurysm is now commonplace, but it has not always been so. Antifibrinolytic agents spawned particular interest in the late 1970s, when many neurosurgeons postponed surgery after a recent hemorrhage. This historical vignette reviews the early views on aneurysmal rupture, rerupture, and the role of fibrinolysis.
Topics: Aneurysm, Ruptured; Antifibrinolytic Agents; History, 20th Century; Humans; Intracranial Aneurysm
PubMed: 29305756
DOI: 10.1007/s12028-017-0496-2 -
Emergency Medicine Clinics of North... Aug 2014The actively bleeding anticoagulated patient presenting to the emergency department requires rapid evaluation and treatment, which is made increasingly complicated by... (Review)
Review
The actively bleeding anticoagulated patient presenting to the emergency department requires rapid evaluation and treatment, which is made increasingly complicated by the ever-evolving antithrombotic treatment options used in medicine. Even with excellent supportive care, the timeliness with which reversal decisions need to be made continues to demand of the emergency practitioner a familiarity with the properties and general characteristics of a variety of antithrombotic agents. Reversal options vary and may include vitamin K, FFP, PCC, rFVIIa, platelets, and desmopressin, among others.
Topics: Antifibrinolytic Agents; Blood Coagulation Factors; Emergency Service, Hospital; Fibrinolytic Agents; Hemorrhage; Hemostasis; Humans; Vitamin K
PubMed: 25060258
DOI: 10.1016/j.emc.2014.04.013