Dependence of clot structure and fibrinolysis on apixaban and clotting activator
Background: Anticoagulants prevent the formation of potentially fatal blood clots. Apixaban is a direct oral anticoagulant that inhibits factor (F)Xa, thereby impeding the conversion of prothrombin into thrombin and the formation of blood clots. Blood clots are held together by fibrin networks that...
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Elsevier
2024-11-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2475037924003091 |
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| author | Rebecca A. Risman Mitali Shroff Julie Goswami Valerie Tutwiler |
| author_facet | Rebecca A. Risman Mitali Shroff Julie Goswami Valerie Tutwiler |
| author_sort | Rebecca A. Risman |
| collection | DOAJ |
| description | Background: Anticoagulants prevent the formation of potentially fatal blood clots. Apixaban is a direct oral anticoagulant that inhibits factor (F)Xa, thereby impeding the conversion of prothrombin into thrombin and the formation of blood clots. Blood clots are held together by fibrin networks that must be broken down (fibrinolysis) to restore blood flow. Fibrinolysis is initiated when tissue plasminogen activator (tPA) converts plasminogen to plasmin, which binds to and degrades a fibrin fiber. The effects of apixaban on clot structure and lysis have been incompletely studied. Objectives: We aimed to study apixaban effects on clot structure, kinetics, and fibrinolysis using thrombin (low or high concentration) or tissue factor (TF) to activate clot formation. Methods: We used a combination of confocal and scanning electron microscopy and turbidity to analyze the structure, formation kinetics, and susceptibility to lysis when plasma was activated with low concentrations of thrombin, high concentrations of thrombin, or TF in the presence or absence of apixaban. Results: We found that the clotting activator and apixaban differentially modulated clot structure and lytic potential. Low thrombin clots with apixaban lysed quickly due to a loose network and FXa cleavage product’s cofactor with tPA; high thrombin clots lysed faster due to FXa cleavage product’s cofactor with tPA; TF generated loose clots with restricted lysis due to their activation of thrombin activatable fibrinolytic inhibitor. Conclusion: Our study elucidates the role of apixaban in fibrinolytic pathways with different clotting activators and can be used for the development of therapeutic strategies using apixaban as a cofactor in fibrinolytic pathways. |
| format | Article |
| id | doaj-art-2c9440c8404f4570b7fb6ba8e4b771bb |
| institution | DOAJ |
| issn | 2475-0379 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj-art-2c9440c8404f4570b7fb6ba8e4b771bb2025-08-20T02:40:07ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792024-11-018810261410.1016/j.rpth.2024.102614Dependence of clot structure and fibrinolysis on apixaban and clotting activatorRebecca A. Risman0Mitali Shroff1Julie Goswami2Valerie Tutwiler3Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USADepartment of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, USADivision of Acute Care Surgery, Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA; Rutgers Acute Care Surgery Research Laboratory (RASR), Department of Surgery, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USADepartment of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA; Correspondence Valerie Tutwiler, Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA.Background: Anticoagulants prevent the formation of potentially fatal blood clots. Apixaban is a direct oral anticoagulant that inhibits factor (F)Xa, thereby impeding the conversion of prothrombin into thrombin and the formation of blood clots. Blood clots are held together by fibrin networks that must be broken down (fibrinolysis) to restore blood flow. Fibrinolysis is initiated when tissue plasminogen activator (tPA) converts plasminogen to plasmin, which binds to and degrades a fibrin fiber. The effects of apixaban on clot structure and lysis have been incompletely studied. Objectives: We aimed to study apixaban effects on clot structure, kinetics, and fibrinolysis using thrombin (low or high concentration) or tissue factor (TF) to activate clot formation. Methods: We used a combination of confocal and scanning electron microscopy and turbidity to analyze the structure, formation kinetics, and susceptibility to lysis when plasma was activated with low concentrations of thrombin, high concentrations of thrombin, or TF in the presence or absence of apixaban. Results: We found that the clotting activator and apixaban differentially modulated clot structure and lytic potential. Low thrombin clots with apixaban lysed quickly due to a loose network and FXa cleavage product’s cofactor with tPA; high thrombin clots lysed faster due to FXa cleavage product’s cofactor with tPA; TF generated loose clots with restricted lysis due to their activation of thrombin activatable fibrinolytic inhibitor. Conclusion: Our study elucidates the role of apixaban in fibrinolytic pathways with different clotting activators and can be used for the development of therapeutic strategies using apixaban as a cofactor in fibrinolytic pathways.http://www.sciencedirect.com/science/article/pii/S2475037924003091anticoagulantapixabanfibrinolysisthrombinthrombosistissue factor |
| spellingShingle | Rebecca A. Risman Mitali Shroff Julie Goswami Valerie Tutwiler Dependence of clot structure and fibrinolysis on apixaban and clotting activator Research and Practice in Thrombosis and Haemostasis anticoagulant apixaban fibrinolysis thrombin thrombosis tissue factor |
| title | Dependence of clot structure and fibrinolysis on apixaban and clotting activator |
| title_full | Dependence of clot structure and fibrinolysis on apixaban and clotting activator |
| title_fullStr | Dependence of clot structure and fibrinolysis on apixaban and clotting activator |
| title_full_unstemmed | Dependence of clot structure and fibrinolysis on apixaban and clotting activator |
| title_short | Dependence of clot structure and fibrinolysis on apixaban and clotting activator |
| title_sort | dependence of clot structure and fibrinolysis on apixaban and clotting activator |
| topic | anticoagulant apixaban fibrinolysis thrombin thrombosis tissue factor |
| url | http://www.sciencedirect.com/science/article/pii/S2475037924003091 |
| work_keys_str_mv | AT rebeccaarisman dependenceofclotstructureandfibrinolysisonapixabanandclottingactivator AT mitalishroff dependenceofclotstructureandfibrinolysisonapixabanandclottingactivator AT juliegoswami dependenceofclotstructureandfibrinolysisonapixabanandclottingactivator AT valerietutwiler dependenceofclotstructureandfibrinolysisonapixabanandclottingactivator |