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Journal of Cardiothoracic and Vascular... Dec 2017
Review
Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Cardiac Surgical Procedures; Humans; Orthopedic Procedures; Postoperative Complications
PubMed: 28457777
DOI: 10.1053/j.jvca.2017.02.029 -
Hamostaseologie Oct 2022In premenopausal women treatment with direct oral anticoagulants (DOACs) can be associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin...
In premenopausal women treatment with direct oral anticoagulants (DOACs) can be associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin K antagonists. These findings come from retrospective or prospective single-center studies and post hoc analysis of regulatory studies in which HMB was not a predefined safety outcome. In most of these publications, there is a lack of information about the use of different contraceptive methods which can influence HMB. Another limitation is the various definitions of HMB, which makes comparison between studies regarding the incidences of HMB difficult.Therefore, prospective studies are urgently needed to investigate the severity and duration of unaffected menstrual bleeding under oral anticoagulation independently of oral contraceptives or intrauterine devices. An ongoing multicenter German registry is aiming to compare the incidence of unaffected HMB in consecutive women of reproductive age (18-50 years) treated with different DOACs because of venous thromboembolism.When HMB occurs during oral anticoagulation, management includes interruption or dose reduction of anticoagulation with the danger of recurrent venous thrombosis, switch to another oral anticoagulant, or additional use of the antifibrinolytic agent tranexamic acid with the potential risk of thrombosis. Concomitant use of either oral hormonal contraceptive therapy or hormone-releasing intrauterine systems can also reduce HMB.
Topics: Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Prospective Studies; Retrospective Studies; Menorrhagia; Antifibrinolytic Agents; Anticoagulants; Contraceptives, Oral
PubMed: 36323281
DOI: 10.1055/a-1891-8187 -
The Cochrane Database of Systematic... Jun 2015Postpartum haemorrhage (PPH) is a common and potentially life-threatening complication of labour. Several options for preventing PPH are available, but further advances... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postpartum haemorrhage (PPH) is a common and potentially life-threatening complication of labour. Several options for preventing PPH are available, but further advances in this field are important, especially the identification of safe, easy to use and cost-effective regimens. Tranexamic acid (TA), which is an antifibrinolytic agent that is used widely to prevent and treat haemorrhage, merits evaluation to assess whether it meets these criteria.
OBJECTIVES
To determine, from the best available evidence, whether TA is effective and safe for preventing PPH in comparison to placebo or no treatment (with or without uterotonic co-treatment), or to uterotonic agents.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 January 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
All published, unpublished and ongoing randomised controlled trials (RCTs) evaluating the use of TA alone or in addition to uterotonics in the third stage of labour or during caesarean section (CS) to prevent PPH.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed for inclusion all the potential studies identified as a result of the search strategy. We entered the data into Review Manager software and checked for accuracy.
MAIN RESULTS
Twelve trials involving 3285 healthy women at low risk of excessive bleeding undergoing elective CS (nine trials, 2453 participants) or spontaneous birth (three trials, 832 participants) satisfied inclusion criteria and contributed data to the analysis. All participants received routine prophylactic uterotonics in accordance with the local guideline in addition to TA or placebo or no intervention. Overall, included studies had moderate risk of bias for random sequence generation, allocation concealment, blinding, selective reporting and low risk of bias for incomplete data. The quality of evidence was also as assessed using GRADE.Blood loss greater than 400 mL or 500 mL, and more than 1000 mL was less common in women who received TA versus placebo or no intervention (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.42 to 0.63, six trials, 1398 women; moderate quality evidence) and (RR 0.40, 95% CI 0.23 to 0.71, six trials, 2093 women; moderate quality evidence), respectively. TA was effective in decreasing the incidence of blood loss greater than 1000 mL in women who had undergone CS (RR 0.43, 95% CI 0.23, 0.78, four trials, 1534 women), but not vaginal birth (RR 0.28, 95% CI 0.06, 1.36, two trials 559 women). The effect of TA on blood loss greater than 500 mL or 400 mL was more pronounced in the group of women having vaginal birth than in women who had CS. Mean blood loss (from delivery until two hours postpartum) was lower in women who received TA versus placebo or no intervention (mean difference MD - 77.79 mL, 95% CI -97.95, -57.64, five trials, 1186 women) and this effect was similar following vaginal birth and CS.Additional medical interventions (moderate quality evidence) and blood transfusions were less frequent in women receiving TA versus placebo or no interventions. Mild side effects such as nausea, vomiting, dizziness were more common with the use of TA (moderate quality evidence). The effect of TA on maternal mortality, severe morbidity and thromboembolic events is uncertain (low quality evidence).
AUTHORS' CONCLUSIONS
TA (in addition to uterotonic medications) decreases postpartum blood loss and prevents PPH and blood transfusions following vaginal birth and CS in women at low risk of PPH based on studies of mixed quality. There is insufficient evidence to draw conclusions about serious side effects, but there is an increase in the incidence of minor side effects with the use of TA. Effects of TA on thromboembolic events and mortality as well as its use in high-risk women should be investigated further.
Topics: Antifibrinolytic Agents; Female; Humans; Injections, Intravenous; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 26079202
DOI: 10.1002/14651858.CD007872.pub3 -
Arteriosclerosis, Thrombosis, and... Jul 2023Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition and rare complication of acute pulmonary embolism. Mechanisms underlying impaired...
BACKGROUND
Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition and rare complication of acute pulmonary embolism. Mechanisms underlying impaired clot resolution and in sustained fibrothrombotic obstruction of the pulmonary arterial bed remain poorly understood. Since defective angiogenesis correlated to defective clot resolution based on observations in surgical material from patients with CTEPH, we aimed to validate its crucial pathogenic role by intrathrombus inhibition of angiogenesis in a novel CTEPH rabbit model.
METHODS
We aimed to compare whether intrathrombus administration of an antifibrinolytic agent, tranexamic acid, or an inhibitor of angiogenesis, SU5416, would contribute to CTEPH progression. Both products were administered on a weekly basis by autologous clot embolization in rabbits. Right ventricular pressure was monitored by telemetry, right ventricular function by transthoracic echocardiography, and a complete pulmonary hemodynamic evaluation was obtained through right heart catheterization. Markers of inflammation, endothelial dysfunction, heart failure, and fibrinolysis were measured in plasma. Pulmonary vessel remodeling was analyzed by immunohistochemistry.
RESULTS
Impairing intrathrombus angiogenesis by repeatedly embolizing autologous blood clots containing SU5416 resulted in elevated mean pulmonary arterial pressure (38 mm Hg), increased indexed pulmonary vascular resistance, and enhanced right ventricular hypertrophy (80%, 1.9-fold, 36%, respectively, compared with rabbits embolized with clots containing an antifibrinolytic agent). This was caused by both obstruction of large pulmonary arteries with fibrothrombotic material and muscularization of pulmonary microvessels, and accompanied by inflammatory cell infiltration and increased circulating endothelin-1.
CONCLUSIONS
The key role of angiogenesis-driven clot resolution was validated in a reliable small-animal model reproducing the major pathophysiological hallmarks of CTEPH.
Topics: Animals; Rabbits; Hypertension, Pulmonary; Antifibrinolytic Agents; Pulmonary Artery; Pulmonary Embolism; Thrombosis; Chronic Disease
PubMed: 37165875
DOI: 10.1161/ATVBAHA.122.317262 -
Current Pharmaceutical Design 2021Spinal surgeries are often accompanied by significant blood loss both intraoperatively and postoperatively. Excessive blood loss caused by surgery may lead to several... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Spinal surgeries are often accompanied by significant blood loss both intraoperatively and postoperatively. Excessive blood loss caused by surgery may lead to several unsatisfactory medical consequences. Tranexamic acid (TXA) is a kind of antifibrinolytic agent that has been widely used in spinal surgery. Currently, it is widely accepted that intravenous TXA (ivTXA) can clearly reduce blood loss in spinal fusion surgeries. Compared with ivTXA, topical TXA (tTXA) seems to be much easier to administer, and this advantage provides a maximum concentration of TXA at the haemorrhagic site with little to no TXA entering the circulation.
OBJECTIVE
To evaluate the effect of tTXA on blood loss during and after spinal surgery via a comprehensive metaanalysis of the published data in randomized controlled trials (RCTs) and other comparative cohort studies.
METHODS
A comprehensive search of PubMed, EMBASE, the Web of Science and the Cochrane Central Register of Controlled Trials was performed for RCTs and other comparative cohort studies on the effect of tTXA on blood loss during and after spinal surgery. The outcomes were total blood loss, hidden blood loss, intraoperative blood loss, total postoperative drainage volume, drainage tube duration postoperatively, drainage volume and drainage of blood content at postoperative day (POD) 1 and POD2, length of hospital stay, number of patients who received a blood transfusion, serum HB level at POD1, operative timespan, side effects and complications. The final search was performed in October, 2020. We followed the PRISMA guideline, and the registration number is INPLASY202160028.
RESULTS
In total, 6 studies with 481 patients were included. tTXA treatment, compared with the control conditions, can significantly reduce the total blood loss, hidden blood loss, total postoperative drainage volume, and number of patients receiving blood transfusions; reduce the drainage volume and drainage of blood content at POD1; shorten the drainage tube duration postoperatively and length of hospital stay; and enhance the serum HB level at POD1 for spinal surgery. tTXA treatment did not significantly influence the intraoperative blood loss, drainage volume or drainage of blood content at POD2 or the operative duration.
CONCLUSION
Compared with control conditions, tTXA has high efficacy in reducing blood loss and drainage volume, enables quick rehabilitation, and has a relatively high level of safety in spinal surgery.
Topics: Administration, Topical; Antifibrinolytic Agents; Blood Loss, Surgical; Blood Transfusion; Humans; Tranexamic Acid
PubMed: 34259138
DOI: 10.2174/1381612827666210713160016 -
Journal of Aerosol Medicine and... Dec 2023The management of severe hemoptysis mainly consists of invasive interventional procedures, including angiographic bronchial artery embolization, various endobronchial...
The management of severe hemoptysis mainly consists of invasive interventional procedures, including angiographic bronchial artery embolization, various endobronchial interventions, and sometimes surgery. However, there are limited effective noninvasive medical therapies available. The objective of this analysis was to evaluate the effectiveness and safety of nebulized tranexamic acid (TXA) administration compared with conventional management in patients with hemoptysis. This Institutional Review Board-approved, single-center, retrospective matched cohort study was performed from January 1, 2018 to March 31, 2021. Electronic health record data were used to identify all adult inpatients with hemoptysis (International Classification of Diseases, Tenth Revision, code R04.2). All patients who received ≥1 dose of nebulized TXA were matched with up to five controls based on available severity criteria (hemoptysis severity, need for mechanical ventilation, and sequential organ failure assessment score at the time of hemoptysis diagnosis) with coarsened exact matching. The primary outcome was the need for invasive interventions for the management of hemoptysis. Secondary outcomes included time to hemoptysis resolution, duration of mechanical ventilation, hemoptysis recurrence, and hospital length of stay. A total of 14 patients were treated with nebulized TXA; they were matched with 58 controls. Patients were 59.7% male, had a median age of 65.5 years, with airway disease (36.1%) being the major etiology of hemoptysis. There was no difference in the number of patients who required an invasive intervention between the TXA (35.7%) versus control group (56.9%), = 0.344. Additionally, no difference was found in the time to hemoptysis resolution ( = 0.050), duration on mechanical ventilation ( = 0.128), hemoptysis recurrence ( = 1.000), or hospital length of stay ( = 0.139). In patients with hemoptysis, nebulized TXA may be considered as a noninvasive option for the management of hemoptysis. However, a larger analysis is warranted to determine the impact of nebulized TXA on invasive interventions for management.
Topics: Adult; Humans; Male; Aged; Female; Tranexamic Acid; Hemoptysis; Antifibrinolytic Agents; Retrospective Studies; Cohort Studies; Administration, Inhalation
PubMed: 37962861
DOI: 10.1089/jamp.2022.0038 -
The Orthopedic Clinics of North America Jan 2016Tranexamic acid has gained recent interest in orthopedics and trauma surgery because of its demonstrated benefit in several clinical trials. It is inexpensive and... (Review)
Review
Tranexamic acid has gained recent interest in orthopedics and trauma surgery because of its demonstrated benefit in several clinical trials. It is inexpensive and effective at reducing blood loss and blood transfusion requirements without a significant increase in morbidity or mortality. The optimal timing, dosing, and route of administration in orthopedics are yet to be elucidated. Significant investigation of tranexamic acid use in joint replacement and spine surgery has promoted its incorporation into the everyday practice of many of these surgeons. The paucity of studies regarding its use in orthopedic trauma has limited its integration into a field that may stand to benefit most from the drug.
Topics: Antifibrinolytic Agents; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Humans; Orthopedic Procedures; Tranexamic Acid; Wounds and Injuries
PubMed: 26614928
DOI: 10.1016/j.ocl.2015.08.014 -
Obstetrics and Gynecology Clinics of... Dec 2015Long-acting reversible contraception (LARC) is the most effective form of reversible contraception. Although most women are satisfied with LARC methods, unscheduled... (Review)
Review
Long-acting reversible contraception (LARC) is the most effective form of reversible contraception. Although most women are satisfied with LARC methods, unscheduled bleeding and spotting are common reasons for method dissatisfaction and discontinuation. This systematic analysis of the current literature delineates treatment options for unscheduled bleeding related to LARC use. Although consistent results are lacking, all devices seem to have the best response to nonsteroidal antiinflammatory drugs for 5 to 7 days or the antifibrinolytic agent tranexamic acid. Additional studies are necessary to identify improved treatment interventions for unscheduled bleeding with LARC use.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Antifibrinolytic Agents; Contraception; Doxycycline; Female; Hormone Antagonists; Humans; Intrauterine Devices, Copper; Intrauterine Devices, Medicated; Levonorgestrel; Matrix Metalloproteinase Inhibitors; Mifepristone; Practice Guidelines as Topic; Time Factors; Tranexamic Acid; Uterine Hemorrhage
PubMed: 26598302
DOI: 10.1016/j.ogc.2015.07.004 -
Medicinal Research Reviews Nov 2014Growing evidence suggests that plasmin is involved in a number of physiological processes in addition to its key role in fibrin cleavage. Plasmin inhibition is critical... (Review)
Review
Growing evidence suggests that plasmin is involved in a number of physiological processes in addition to its key role in fibrin cleavage. Plasmin inhibition is critical in preventing adverse consequences arising from plasmin overactivity, e.g., blood loss that may follow cardiac surgery. Aprotinin was widely used as an antifibrinolytic drug before its discontinuation in 2008. Tranexamic acid and ε-aminocaproic acid, two small molecule plasmin inhibitors, are currently used in the clinic. Several molecules have been designed utilizing covalent, but reversible, chemistry relying on reactive cyclohexanones, nitrile warheads, and reactive aldehyde peptidomimetics. Other major classes of plasmin inhibitors include the cyclic peptidomimetics and polypeptides of the Kunitz and Kazal-type. Allosteric inhibitors of plasmin have also been designed including small molecule lysine analogs that bind to plasmin's kringle domain(s) and sulfated glycosaminoglycan mimetics that bind to plasmin's catalytic domain. Plasmin inhibitors have also been explored for resolving other disease states including cell metastasis, cell proliferation, angiogenesis, and embryo implantation. This review highlights functional and structural aspects of plasmin inhibitors with the goal of advancing their design.
Topics: Antifibrinolytic Agents; Aprotinin; Benzamidines; Dipeptides; Drug Design; Fibrinolysin; Fibrinolysis; Guanidines; Humans; Phenylalanine; Serine Proteinase Inhibitors
PubMed: 24659483
DOI: 10.1002/med.21315 -
Lancet (London, England) Jul 2021
Topics: Antifibrinolytic Agents; Humans; Subarachnoid Hemorrhage; Tranexamic Acid
PubMed: 34217395
DOI: 10.1016/S0140-6736(21)00573-0