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Cell Chemical Biology Dec 2021Aberrant protein citrullination is associated with many pathologies; however, the specific effects of this modification remain unknown. We have previously demonstrated...
Aberrant protein citrullination is associated with many pathologies; however, the specific effects of this modification remain unknown. We have previously demonstrated that serine protease inhibitors (SERPINs) are highly citrullinated in rheumatoid arthritis (RA) patients. These citrullinated SERPINs include antithrombin, antiplasmin, and t-PAI, which regulate the coagulation and fibrinolysis cascades. Notably, citrullination eliminates their inhibitory activity. Here, we demonstrate that citrullination of antithrombin and t-PAI impairs their binding to their cognate proteases. By contrast, citrullination converts antiplasmin into a substrate. We recapitulate the effects of SERPIN citrullination using in vitro plasma clotting and fibrinolysis assays. Moreover, we show that citrullinated antithrombin and antiplasmin are increased and decreased in a deep vein thrombosis (DVT) model, accounting for how SERPIN citrullination shifts the equilibrium toward thrombus formation. These data provide a direct link between increased citrullination and the risk of thrombosis in autoimmunity and indicate that aberrant SERPIN citrullination promotes pathological thrombus formation.
Topics: Animals; Antifibrinolytic Agents; Antithrombins; Disease Models, Animal; Female; Male; Mice; Mice, Inbred C57BL; Peptide Hydrolases; Plasminogen Inactivators; Serine Proteinase Inhibitors; Venous Thrombosis
PubMed: 34352225
DOI: 10.1016/j.chembiol.2021.07.009 -
Zeitschrift Fur Orthopadie Und... Oct 2023The application of tranexamic acid (TXA) during endoprosthetic surgical procedures has significantly increased in recent years. Due its ability to reduce perioperative...
The application of tranexamic acid (TXA) during endoprosthetic surgical procedures has significantly increased in recent years. Due its ability to reduce perioperative blood loss and avert the need for blood transfusions as well as wound drainage, TXA is becoming part of a 'standard practice'. However, TXA is currently not approved for the application during endoprosthetic procedures and therefore, a benefit-risk analysis should always be conducted. Prophylactic administration of TXA without prior patient consent is only justified if fibrinolytic bleeding is expected and there are no contraindications or relevant risk factors for thromboembolic complications. Respectively, no patient consent is required when a therapeutic dose of TXA is administered in the context of fibrinolytic bleeding. The following guidelines provide updated recommendations based on the current state of knowledge on TXA optimal timing, routes of administration and dosing regimen.
Topics: Humans; Antifibrinolytic Agents; Tranexamic Acid; Blood Loss, Surgical; Blood Transfusion
PubMed: 37336245
DOI: 10.1055/a-2055-8178 -
Foot & Ankle Specialist Aug 2022Tranexamic acid (TXA) has become a commonly used perioperative intervention in total joint arthroplasty, shoulder and knee arthroscopy, and spinal procedures in order to... (Review)
Review
Tranexamic acid (TXA) has become a commonly used perioperative intervention in total joint arthroplasty, shoulder and knee arthroscopy, and spinal procedures in order to minimize blood loss, hematoma formation, hemarthrosis, and wound healing complications. There is a potential role for TXA use in foot and ankle procedures, with limited studies suggesting a potential benefit in minimizing postoperative wound complications and blood loss without an increased risk of thromboembolic events. In light of the profound clinical and financial impact of TXA use in other orthopaedic subspecialties and the early successes in foot and ankle surgery, we aim to provide more information about TXA and its use in foot and ankle surgery. Therefore, the purpose of this review is to perform a comprehensive literature review on the topic of TXA use in foot and ankle procedures in order to describe the pertinent available literature on the use of TXA in orthopaedic surgery and its implications specifically in foot and ankle surgery. It is our aim to identify potential benefits and shortcomings in the available evidence on TXA use for foot and ankle surgery in hopes to (1) best inform foot and ankle surgeons where beneficial and safe and (2) inspire further research on this topic as it relates to clinical management for foot and ankle patients. .
Topics: Ankle; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Humans; Tranexamic Acid
PubMed: 33401927
DOI: 10.1177/1938640020983639 -
Brazilian Journal of Anesthesiology... 2020
Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Dose-Response Relationship, Drug; Humans; Tranexamic Acid
PubMed: 32773239
DOI: 10.1016/j.bjan.2020.07.001 -
Seminars in Cell & Developmental Biology May 2020Most chronic diseases involving inflammation have a fibrotic component that involves remodeling and excess accumulation of extracellular matrix components. Left... (Review)
Review
Most chronic diseases involving inflammation have a fibrotic component that involves remodeling and excess accumulation of extracellular matrix components. Left unchecked, fibrosis leads to organ failure and death. Mesenchymal stromal cells (MSCs) are emerging as a potent cell-based therapy for a wide spectrum of fibrotic conditions due to their immunomodulatory, anti-inflammatory and anti-fibrotic properties. This review provides an overview of known mechanisms by which MSCs mediate their anti-fibrotic actions and in relation to animal models of pulmonary, liver, renal and cardiac fibrosis. Recent MSC clinical trials results in liver, lung, skin, kidney and hearts are discussed and next steps for future MSC-based therapies including pre-activated or genetically-modified cells, or extracellular vesicles are also considered.
Topics: Animals; Antifibrinolytic Agents; Fibrosis; Humans; Mesenchymal Stem Cells
PubMed: 31757583
DOI: 10.1016/j.semcdb.2019.10.014 -
International Journal of Molecular... Jan 2022Aortic aneurysms are sometimes associated with enhanced-fibrinolytic-type disseminated intravascular coagulation (DIC). In enhanced-fibrinolytic-type DIC, both... (Review)
Review
Aortic aneurysms are sometimes associated with enhanced-fibrinolytic-type disseminated intravascular coagulation (DIC). In enhanced-fibrinolytic-type DIC, both coagulation and fibrinolysis are markedly activated. Typical cases show decreased platelet counts and fibrinogen levels, increased concentrations of fibrin/fibrinogen degradation products (FDP) and D-dimer, and increased FDP/D-dimer ratios. Thrombin-antithrombin complex or prothrombin fragment 1 + 2, as markers of coagulation activation, and plasmin-α plasmin inhibitor complex, a marker of fibrinolytic activation, are all markedly increased. Prolongation of prothrombin time (PT) is not so obvious, and the activated partial thromboplastin time (APTT) is rather shortened in some cases. As a result, DIC can be neither diagnosed nor excluded based on PT and APTT alone. Many of the factors involved in coagulation and fibrinolysis activation are serine proteases. Treatment of enhanced-fibrinolytic-type DIC requires consideration of how to control the function of these serine proteases. The cornerstone of DIC treatment is treatment of the underlying pathology. However, in some cases surgery is either not possible or exacerbates the DIC associated with aortic aneurysm. In such cases, pharmacotherapy becomes even more important. Unfractionated heparin, other heparins, synthetic protease inhibitors, recombinant thrombomodulin, and direct oral anticoagulants (DOACs) are agents that inhibit serine proteases, and all are effective against DIC. Inhibition of activated coagulation factors by anticoagulants is key to the treatment of DIC. Among them, DOACs can be taken orally and is useful for outpatient treatment. Combination therapy of heparin and nafamostat allows fine-adjustment of anticoagulant and antifibrinolytic effects. While warfarin is an anticoagulant, this agent is ineffective in the treatment of DIC because it inhibits the production of coagulation factors as substrates without inhibiting activated coagulation factors. In addition, monotherapy using tranexamic acid in cases of enhanced-fibrinolytic-type DIC may induce fatal thrombosis. If tranexamic acid is needed for DIC, combination with anticoagulant therapy is of critical importance.
Topics: Anticoagulants; Antifibrinolytic Agents; Aortic Aneurysm; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinolysis; Heparin; Humans; Partial Thromboplastin Time; Prothrombin Time; alpha-2-Antiplasmin
PubMed: 35163216
DOI: 10.3390/ijms23031296 -
Internal and Emergency Medicine Jan 2023Tranexamic acid (TXA) is a common haemorrhage control agent in both emergency department (ED) settings and intra-operatively. While efficacy and potential harms are... (Review)
Review
Tranexamic acid (TXA) is a common haemorrhage control agent in both emergency department (ED) settings and intra-operatively. While efficacy and potential harms are well-studied, there are no overviews of reviews completed on TXA efficacy in the ED setting. We set out to provide an overview of systematic reviews on TXA efficacy in trauma, gastrointestinal bleeding, and subarachnoid haemorrhage in the ED setting, with outcomes including short and long-term mortality, thromboembolic (TE) events, and whether bleeding continued. Our review is guided by the PRIOR statement. We searched Pubmed, Medline, and EMBASE using broad search terms for systematic reviews, and calculated pooled relative-risk ratios using random and fixed-effects modelling from these studies. A risk-of-bias assessment was also completed for each review. We identified 13 systematic reviews for inclusion, with a variety of different outcomes. We identified improvements in 24-h mortality for trauma (RR 0.88, 95% CI 0.84-0.92) and gastrointestinal bleeds (RR 0.30, 95% CI 0.23-0.39), and decreased long-term gastrointestinal bleed mortality (RR 0.57, 95% CI 0.48-0.69). We also identified an increase in TE risk in gastrointestinal bleeding scenarios (RR 1.45, 95% CI 1.09-1.94), but no other clinical scenarios. TXA is effective in reducing mortality following trauma and gastrointestinal bleeds, however, there is limited evidence at this time to support TXA administration in the context of subarachnoid haemorrhage. TE risk is elevated when used in gastrointestinal bleeds. Selective use in high-risk patients may be warranted. TXA should strongly be considered in management in ED and prehospital settings.
Topics: Humans; Tranexamic Acid; Antifibrinolytic Agents; Subarachnoid Hemorrhage; Systematic Reviews as Topic; Gastrointestinal Hemorrhage; Emergency Medicine
PubMed: 36562900
DOI: 10.1007/s11739-022-03155-x -
Journal of Cardiothoracic and Vascular... Oct 2022
Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Humans; Tranexamic Acid
PubMed: 35840472
DOI: 10.1053/j.jvca.2022.05.034 -
Chest May 2023
Topics: Humans; Tranexamic Acid; Hemoptysis; Antifibrinolytic Agents; Treatment Outcome
PubMed: 37164570
DOI: 10.1016/j.chest.2022.12.011 -
Acta Ortopedica Mexicana 2021Tranexamic acid is an antifibrinolytic drug which has been used in many disciplines of Medicine, as well as in Orthopaedics and Traumatology, with the objective of... (Review)
Review
INTRODUCTION
Tranexamic acid is an antifibrinolytic drug which has been used in many disciplines of Medicine, as well as in Orthopaedics and Traumatology, with the objective of diminishing and preventing blood loss and the necessity of allogenic blood transfusion. This study has the objective to demonstrate the uses, indications and contraindications of tranexamic acid in the different subspecialties of Orthopaedics and Traumatology.
MATERIAL AND METHODS
A through search was performed looking at the most recent evidence regarding the use of tranexamic acid in the different subspecialties of Orthopaedics and Traumatology, as well as its indications, contraindications and adverse effects.
RESULTS
Tranexamic acid has a great amount of applications in Orthopaedics and Traumatology, especially in primary and revision knee and hip arthroplasties, spine surgery and trauma. It has been observed that tranexamic acid is effective in diminishing perioperative bleeding, less necessity of blood transfusion, among other benefits. Tranexamic acid is a safe drug, which does not increase the risk of developing thrombotic events in healthy patients. There are a number of administration routes of tranexamic acid as well as many dosage regimens, all being efficient. Therefore, no standardization regarding the best administration route and most effective dose has been established.
CONCLUSIONS
Tranexamic acid is a safe and effective drug for diminishing perioperative bleeding and to avoid the necessity of blood transfusion, with many applications in Orthopaedics and Traumatology.
Topics: Antifibrinolytic Agents; Arthroplasty, Replacement; Humans; Orthopedics; Tranexamic Acid; Traumatology
PubMed: 35793255
DOI: No ID Found