Impact of antiplatelet therapy on hemostatic plug formation in the setting of thrombocytopenia
Background: Antiplatelet therapy (APT), mainly aspirin and P2Y12 receptor inhibitors, reduces the incidence of recurrent arterial thrombosis but also increases bleeding risk. Therefore, management of APT in patients with thrombocytopenia, itself an independent risk factor for bleeding, is a clinical...
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Elsevier
2025-01-01
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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/S2475037924003674 |
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| author | Robert H. Lee Abigail Ballard-Kordeliski Summer R. Jones Wolfgang Bergmeier |
| author_facet | Robert H. Lee Abigail Ballard-Kordeliski Summer R. Jones Wolfgang Bergmeier |
| author_sort | Robert H. Lee |
| collection | DOAJ |
| description | Background: Antiplatelet therapy (APT), mainly aspirin and P2Y12 receptor inhibitors, reduces the incidence of recurrent arterial thrombosis but also increases bleeding risk. Therefore, management of APT in patients with thrombocytopenia, itself an independent risk factor for bleeding, is a clinical challenge with few evidence-based guidelines. Data are lacking on the combined impact of thrombocytopenia and APT on hemostasis. Objectives: To systematically investigate the combined effect of thrombocytopenia and APT in mouse models of hemostasis and thrombosis. Methods: Platelet-depleted mice were repleted with donor platelets inhibited with aspirin and/or clopidogrel at low (<1 × 108/mL) or normal (>2) platelet counts. Hemostasis was assessed in the saphenous vein laser injury model, and thrombosis was assessed in the carotid artery ferric chloride model. Results: In the saphenous vein laser injury model, neither single nor dual APT significantly increased bleeding compared with vehicle at platelet counts >2 × 108/mL. However, for platelet counts <1, clopidogrel prolonged the time to the first hemostatic plug, and dual APT prolonged the time to the first plug and total bleeding time compared with vehicle and aspirin treatment. In the carotid artery ferric chloride thrombosis model, clopidogrel was entirely protected against platelet-rich thrombus formation, while aspirin had minimal effect. Conclusion: Our experimental data suggests that for severe thrombocytopenia, single APT provides an appropriate balance of antithrombotic effect and limited bleeding, with clopidogrel demonstrating a greater antithrombotic effect but slightly increased bleeding compared with aspirin. |
| format | Article |
| id | doaj-art-93cc81ecc7984e839c3917077ee586d3 |
| institution | Kabale University |
| issn | 2475-0379 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj-art-93cc81ecc7984e839c3917077ee586d32025-01-22T05:43:06ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-01-0191102672Impact of antiplatelet therapy on hemostatic plug formation in the setting of thrombocytopeniaRobert H. Lee0Abigail Ballard-Kordeliski1Summer R. Jones2Wolfgang Bergmeier3Correspondence Robert H. Lee and Wolfgang Bergmeier, University of North Carolina at Chapel Hill, 116 Manning Drive, 8212A Mary Ellen Jones Bldg, CB7035, Chapel Hill, NC 27599, USA.; Department of Biochemistry and Biophysics, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USADepartment of Biochemistry and Biophysics, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USADepartment of Biochemistry and Biophysics, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USACorrespondence Robert H. Lee and Wolfgang Bergmeier, University of North Carolina at Chapel Hill, 116 Manning Drive, 8212A Mary Ellen Jones Bldg, CB7035, Chapel Hill, NC 27599, USA.; Department of Biochemistry and Biophysics, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USABackground: Antiplatelet therapy (APT), mainly aspirin and P2Y12 receptor inhibitors, reduces the incidence of recurrent arterial thrombosis but also increases bleeding risk. Therefore, management of APT in patients with thrombocytopenia, itself an independent risk factor for bleeding, is a clinical challenge with few evidence-based guidelines. Data are lacking on the combined impact of thrombocytopenia and APT on hemostasis. Objectives: To systematically investigate the combined effect of thrombocytopenia and APT in mouse models of hemostasis and thrombosis. Methods: Platelet-depleted mice were repleted with donor platelets inhibited with aspirin and/or clopidogrel at low (<1 × 108/mL) or normal (>2) platelet counts. Hemostasis was assessed in the saphenous vein laser injury model, and thrombosis was assessed in the carotid artery ferric chloride model. Results: In the saphenous vein laser injury model, neither single nor dual APT significantly increased bleeding compared with vehicle at platelet counts >2 × 108/mL. However, for platelet counts <1, clopidogrel prolonged the time to the first hemostatic plug, and dual APT prolonged the time to the first plug and total bleeding time compared with vehicle and aspirin treatment. In the carotid artery ferric chloride thrombosis model, clopidogrel was entirely protected against platelet-rich thrombus formation, while aspirin had minimal effect. Conclusion: Our experimental data suggests that for severe thrombocytopenia, single APT provides an appropriate balance of antithrombotic effect and limited bleeding, with clopidogrel demonstrating a greater antithrombotic effect but slightly increased bleeding compared with aspirin.http://www.sciencedirect.com/science/article/pii/S2475037924003674aspirinclopidogreldual antiplatelet therapyintravital microscopythrombocytopenia |
| spellingShingle | Robert H. Lee Abigail Ballard-Kordeliski Summer R. Jones Wolfgang Bergmeier Impact of antiplatelet therapy on hemostatic plug formation in the setting of thrombocytopenia Research and Practice in Thrombosis and Haemostasis aspirin clopidogrel dual antiplatelet therapy intravital microscopy thrombocytopenia |
| title | Impact of antiplatelet therapy on hemostatic plug formation in the setting of thrombocytopenia |
| title_full | Impact of antiplatelet therapy on hemostatic plug formation in the setting of thrombocytopenia |
| title_fullStr | Impact of antiplatelet therapy on hemostatic plug formation in the setting of thrombocytopenia |
| title_full_unstemmed | Impact of antiplatelet therapy on hemostatic plug formation in the setting of thrombocytopenia |
| title_short | Impact of antiplatelet therapy on hemostatic plug formation in the setting of thrombocytopenia |
| title_sort | impact of antiplatelet therapy on hemostatic plug formation in the setting of thrombocytopenia |
| topic | aspirin clopidogrel dual antiplatelet therapy intravital microscopy thrombocytopenia |
| url | http://www.sciencedirect.com/science/article/pii/S2475037924003674 |
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