Tranexamic acid for haemostasis and beyond: does dose matter?
Abstract Tranexamic acid (TXA) is a widely used antifibrinolytic agent that has been used since the 1960’s to reduce blood loss in various conditions. TXA is a lysine analogue that competes for the lysine binding sites in plasminogen and tissue-type plasminogen activator impairing its interaction wi...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Thrombosis Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12959-023-00540-0 |
| _version_ | 1797451741557424128 |
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| author | Tammy Lam Robert L. Medcalf Geoffrey C. Cloud Paul S. Myles Charithani B. Keragala |
| author_facet | Tammy Lam Robert L. Medcalf Geoffrey C. Cloud Paul S. Myles Charithani B. Keragala |
| author_sort | Tammy Lam |
| collection | DOAJ |
| description | Abstract Tranexamic acid (TXA) is a widely used antifibrinolytic agent that has been used since the 1960’s to reduce blood loss in various conditions. TXA is a lysine analogue that competes for the lysine binding sites in plasminogen and tissue-type plasminogen activator impairing its interaction with the exposed lysine residues on the fibrin surface. The presence of TXA therefore, impairs the plasminogen and tPA engagement and subsequent plasmin generation on the fibrin surface, protecting fibrin clot from proteolytic degradation. However, critical lysine binding sites for plasmin(ogen) also exist on other proteins and on various cell-surface receptors allowing plasmin to exert potent effects on other targets that are unrelated to classical fibrinolysis, notably in relation to immunity and inflammation. Indeed, TXA was reported to significantly reduce post-surgical infection rates in patients after cardiac surgery unrelated to its haemostatic effects. This has provided an impetus to consider TXA in other indications beyond inhibition of fibrinolysis. While there is extensive literature on the optimal dosage of TXA to reduce bleeding rates and transfusion needs, it remains to be determined if these dosages also apply to blocking the non-canonical effects of plasmin. |
| first_indexed | 2024-03-09T14:58:50Z |
| format | Article |
| id | doaj.art-2b1241028ebe4d3aa15910dc9fd65b57 |
| institution | Directory Open Access Journal |
| issn | 1477-9560 |
| language | English |
| last_indexed | 2024-03-09T14:58:50Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Thrombosis Journal |
| spelling | doaj.art-2b1241028ebe4d3aa15910dc9fd65b572023-11-26T14:00:27ZengBMCThrombosis Journal1477-95602023-09-0121111210.1186/s12959-023-00540-0Tranexamic acid for haemostasis and beyond: does dose matter?Tammy Lam0Robert L. Medcalf1Geoffrey C. Cloud2Paul S. Myles3Charithani B. Keragala4Australian Centre for Blood Diseases, Monash AMREP Building, Monash UniversityAustralian Centre for Blood Diseases, Monash AMREP Building, Monash UniversityDepartment of Clinical Neuroscience, Central Clinical School, Monash UniversityDepartment of Anaesthesiology and Perioperative Medicine, Alfred HospitalAustralian Centre for Blood Diseases, Monash AMREP Building, Monash UniversityAbstract Tranexamic acid (TXA) is a widely used antifibrinolytic agent that has been used since the 1960’s to reduce blood loss in various conditions. TXA is a lysine analogue that competes for the lysine binding sites in plasminogen and tissue-type plasminogen activator impairing its interaction with the exposed lysine residues on the fibrin surface. The presence of TXA therefore, impairs the plasminogen and tPA engagement and subsequent plasmin generation on the fibrin surface, protecting fibrin clot from proteolytic degradation. However, critical lysine binding sites for plasmin(ogen) also exist on other proteins and on various cell-surface receptors allowing plasmin to exert potent effects on other targets that are unrelated to classical fibrinolysis, notably in relation to immunity and inflammation. Indeed, TXA was reported to significantly reduce post-surgical infection rates in patients after cardiac surgery unrelated to its haemostatic effects. This has provided an impetus to consider TXA in other indications beyond inhibition of fibrinolysis. While there is extensive literature on the optimal dosage of TXA to reduce bleeding rates and transfusion needs, it remains to be determined if these dosages also apply to blocking the non-canonical effects of plasmin.https://doi.org/10.1186/s12959-023-00540-0Tranexamic acidFibrinolysisThrombosisImmunityAmyloidPharmacology |
| spellingShingle | Tammy Lam Robert L. Medcalf Geoffrey C. Cloud Paul S. Myles Charithani B. Keragala Tranexamic acid for haemostasis and beyond: does dose matter? Thrombosis Journal Tranexamic acid Fibrinolysis Thrombosis Immunity Amyloid Pharmacology |
| title | Tranexamic acid for haemostasis and beyond: does dose matter? |
| title_full | Tranexamic acid for haemostasis and beyond: does dose matter? |
| title_fullStr | Tranexamic acid for haemostasis and beyond: does dose matter? |
| title_full_unstemmed | Tranexamic acid for haemostasis and beyond: does dose matter? |
| title_short | Tranexamic acid for haemostasis and beyond: does dose matter? |
| title_sort | tranexamic acid for haemostasis and beyond does dose matter |
| topic | Tranexamic acid Fibrinolysis Thrombosis Immunity Amyloid Pharmacology |
| url | https://doi.org/10.1186/s12959-023-00540-0 |
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