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Anesthesia and Analgesia Jul 2014
Topics: Antifibrinolytic Agents; Cardiopulmonary Bypass; Coronary Artery Bypass; Female; Humans; Male; Serine Proteinase Inhibitors
PubMed: 24945119
DOI: 10.1213/ANE.0000000000000225 -
The Journal of Pharmacology and... Apr 2002Application of 4-(aminomethyl)cyclohexanecarboxylic acid (tranexamic acid; TAMCA) to the central nervous system (CNS) has been shown to result in hyperexcitability and...
Application of 4-(aminomethyl)cyclohexanecarboxylic acid (tranexamic acid; TAMCA) to the central nervous system (CNS) has been shown to result in hyperexcitability and convulsions. However, the mechanisms underlying this action are unknown. In the present study, we demonstrate that TAMCA binds to the gamma-aminobutyric acid (GABA) binding site of GABA(A) receptors in membranes from rat cerebral cortex and does not interfere with N-methyl-D-aspartate receptors. Patch-clamp studies using human embryonic kidney cells transiently transfected with recombinant GABA(A) receptors composed of alpha 1 beta 2 gamma 2 subunits showed that TAMCA did not activate these receptors but dose dependently blocked GABA-induced chloride ion flux with an IC(50) of 7.1 +/- 3.1 mM. Application of TAMCA to the lumbar spinal cord of rats resulted in dose-dependent hyperexcitability, which was completely blocked by coapplication of the GABA(A) receptor agonist muscimol. These results indicate that TAMCA may induce hyperexcitability by blocking GABA-driven inhibition of the CNS.
Topics: Animals; Antifibrinolytic Agents; Binding, Competitive; Brain Chemistry; Cell Line; Dizocilpine Maleate; Dose-Response Relationship, Drug; GABA Agonists; GABA Antagonists; GABA-A Receptor Antagonists; Hindlimb; Humans; Male; Membrane Potentials; Membranes; Muscimol; Patch-Clamp Techniques; Rats; Receptors, N-Methyl-D-Aspartate; Seizures; Spinal Cord; Tranexamic Acid
PubMed: 11907171
DOI: 10.1124/jpet.301.1.168 -
Clinical and Applied... 2022Acute promyelocytic leukemia (APL) usually presents with a series of coagulation-anticoagulation disturbance. Early administration of All-trans retinoic acid (ATRA) can... (Review)
Review
Acute promyelocytic leukemia (APL) usually presents with a series of coagulation-anticoagulation disturbance. Early administration of All-trans retinoic acid (ATRA) can reduce the risk of bleeding, but the potential for thrombosis needs to be addressed in some cases. The role of arsenic agent in correcting coagulation disorder remains to be studied, but oral arsenic agent shows potential advantages in coagulation recovery compared with intravenous agent, and chemotherapy can aggravate the progress of coagulation disease. In addition to early application of ATRA, avoiding invasive procedures and transfusion support can reduce the risk of bleeding. Whether the administration of heparin, thrombomodulin, recombinant factor VIIa or antifibrinolytics reduces the risk of bleeding and thrombosis associated with APL remains to be further explored, and their routine use outside of clinical trials is not recommended. This article reviews the effects of related drugs on coagulation-anticoagulation balance in APL patients.
Topics: Antifibrinolytic Agents; Antineoplastic Agents; Arsenic Trioxide; Blood Coagulation; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Thrombosis; Tretinoin
PubMed: 35187963
DOI: 10.1177/10760296221080166 -
Orthopedics 2016Perioperative bleeding and postsurgical hemorrhage are common in invasive surgical procedures, including orthopedic surgery. Tranexamic acid (TXA) is a pharmacologic... (Review)
Review
Perioperative bleeding and postsurgical hemorrhage are common in invasive surgical procedures, including orthopedic surgery. Tranexamic acid (TXA) is a pharmacologic agent that acts through an antifibrinolytic mechanism to stabilize formed clots and reduce active bleeding. It has been used successfully in orthopedics to reduce perioperative blood loss, particularly in total hip and knee arthroplasty and spine surgery. Numerous research studies have reported favorable safety and efficacy in orthopedic cases, although there is no universal standard on its administration and its use has not yet become the standard of practice. Reported administration methods often depend on the surgeon's preference, with both topical and intravenous routes showing efficacy. The type and anatomic site of the surgery seem to influence the decision making but also result in conflicting opinions. Reported complication rates with TXA use are low. The incidence of both arterial and venous thromboembolic events, particularly deep venous thrombosis and pulmonary embolism, has not been found to be significantly different with TXA use for healthy patients. The route of administration and dosage do not appear to affect complication rates either. However, data on patients with higher-risk conditions are deficient. In addition, TXA has shown potential to reduce blood loss, transfusion rates and volumes, perioperative hemoglobin change, and hospital-related costs at various degrees among the published studies. Conservation of blood products, reduced laboratory costs, and shorter hospital stays are likely the major factors driving the cost savings associated with TXA use. This article reviews current data supporting the safety, efficacy, and cost-effectiveness of TXA in orthopedic surgery.
Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Cost-Benefit Analysis; Humans; Orthopedic Procedures; Orthopedics; Postoperative Hemorrhage; Tranexamic Acid
PubMed: 26942474
DOI: 10.3928/01477447-20160301-05 -
ANZ Journal of Surgery Apr 2020
Topics: Antifibrinolytic Agents; Blood Coagulation; Fibrin; Fibrinolysin; Fibrinolysis; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Time Factors; Tranexamic Acid; Wounds and Injuries
PubMed: 32339417
DOI: 10.1111/ans.15541 -
Acta Medica Scandinavica Oct 1961
Topics: Amino Acids; Aminocaproic Acid; Antifibrinolytic Agents; Hemorrhagic Disorders
PubMed: 14479884
DOI: 10.1111/j.0954-6820.1961.tb00264.x -
Current Opinion in Hematology Nov 2018We review recent articles pertaining to the use of tranexamic acid (TXA) in populations at risk for massive transfusion. Although there are no recent studies that... (Review)
Review
PURPOSE OF REVIEW
We review recent articles pertaining to the use of tranexamic acid (TXA) in populations at risk for massive transfusion. Although there are no recent studies that specifically examine the use of TXA in massive transfusion protocols (MTPs), there are a few studies with subgroups of massive transfusion patients.
RECENT FINDINGS
In recent years, many publications have discussed outcomes and safety associated with the addition of TXA to treatment plans for bleeding pediatric, trauma, and postpartum hemorrhage patients. In general, TXA appears to decrease mortality and transfusion requirements.
SUMMARY
TXA was shown to decrease mortality in several bleeding populations. It is now a common addition to MTPs. There is conflicting evidence regarding the potential of TXA as a risk factor for thrombotic events. Ongoing studies should provide additional evidence regarding the thrombotic risk of TXA in massive transfusion.
Topics: Antifibrinolytic Agents; Blood Transfusion; Humans; Thrombosis; Tranexamic Acid
PubMed: 30124475
DOI: 10.1097/MOH.0000000000000457 -
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 -
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 -
Neurocritical Care Apr 2021Almost two-thirds of patients with severe traumatic brain injury (TBI) develop some form of hemostatic disturbance, which contributes to poor outcome. While the initial... (Review)
Review
Almost two-thirds of patients with severe traumatic brain injury (TBI) develop some form of hemostatic disturbance, which contributes to poor outcome. While the initial head injury often leads to impaired clot formation, TBI is also associated with an increased risk of thrombosis. Most likely there is a progression from early bleeding to a later prothrombotic state. In this paper, we systematically review the literature on the time course of hemostatic disruptions following TBI. A MEDLINE search was performed for TBI studies reporting the trajectory of hemostatic assays over time. The search yielded 5,049 articles, of which 4,910 were excluded following duplicate removal as well as title and abstract review. Full-text assessment of the remaining articles yielded 33 studies that were included in the final review. We found that the first hours after TBI are characterized by coagulation cascade dysfunction and hyperfibrinolysis, both of which likely contribute to lesion progression. This is then followed by platelet dysfunction and decreased platelet count, the clinical implication of which remains unclear. Later, a poorly defined prothrombotic state emerges, partly due to fibrinolysis shutdown and hyperactive platelets. In the clinical setting, early administration of the antifibrinolytic agent tranexamic acid has proved effective in reducing head-injury-related mortality in a subgroup of TBI patients. Further studies evaluating the time course of hemostatic disruptions after TBI are warranted in order to identify windows of opportunity for potential treatment options.
Topics: Antifibrinolytic Agents; Blood Coagulation Disorders; Brain Injuries, Traumatic; Hemostatics; Humans; Tranexamic Acid
PubMed: 32607969
DOI: 10.1007/s12028-020-01037-8