Sex differences in flow cytometry–based platelet reactivity in stable outpatients suspected of myocardial ischemia
Abstract Background Antiplatelet therapy is the mainstay of secondary prevention of cardiovascular events. Studies suggest that women do not obtain equal therapeutic benefit from antiplatelet therapy compared with men. The link between sex differences in platelet biology and response to antiplatelet...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-07-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/rth2.12344 |
| _version_ | 1797709856452378624 |
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| author | Farahnaz Waissi Mirthe Dekker Ingrid E.M. Bank Suzanne J.A. Korporaal Rolf T. Urbanus Gert J. deBorst Gerard Pasterkamp Asbjorn M. Scholtens Diederick E. Grobbee Arend Mosterd Dominique P.V. deKleijn Leo Timmers |
| author_facet | Farahnaz Waissi Mirthe Dekker Ingrid E.M. Bank Suzanne J.A. Korporaal Rolf T. Urbanus Gert J. deBorst Gerard Pasterkamp Asbjorn M. Scholtens Diederick E. Grobbee Arend Mosterd Dominique P.V. deKleijn Leo Timmers |
| author_sort | Farahnaz Waissi |
| collection | DOAJ |
| description | Abstract Background Antiplatelet therapy is the mainstay of secondary prevention of cardiovascular events. Studies suggest that women do not obtain equal therapeutic benefit from antiplatelet therapy compared with men. The link between sex differences in platelet biology and response to antiplatelet therapies is unclear. We therefore investigated the role of sex differences in platelet reactivity in a cohort of outpatients with chest pain, in response to treatment with antiplatelet agents. Methods Platelet reactivity was measured in 382 randomly selected patients participating in the Myocardial Ischemia Detection by Circulating Biomarkers (MYOMARKER) study, an observational cohort study of outpatients suspected of myocardial ischemia. In all patients, blood was collected during diagnostic workup, and platelet reactivity was assessed with a flow cytometry–based platelet activation test that quantifies both platelet degranulation (P‐selectin expression) and platelet aggregation (fibrinogen binding to integrin αIIbβ3) in whole blood. Results Platelet reactivity was higher in women compared with men when activated with protease activating receptor 1–activating peptide SFLLRN (PAR1‐AP) and adenosine 5′‐phosphate (ADP), independent of age, basal activation status, estimated glomerular filtration rate < 60, platelet count, statin use, the use of P2Y12 inhibitors, or the use of aspirin. P2Y12 inhibitor use strongly reduced fibrinogen binding after stimulation with PAR1‐AP, but only slightly reduced platelet P‐selectin expression. Calculation of the relative inhibition in P2Y12 users indicated 62% inhibition of the response toward ADP. Stratified analysis showed that women (n = 14) using P2Y12 inhibitors showed less inhibition of fibrinogen binding after PAR1‐AP stimulation than men (n = 38) using P2Y12 inhibitors. Conclusions These findings call for further study of differential effects of P2Y12 inhibitors in women with suspected myocardial ischemia. |
| first_indexed | 2024-03-12T06:42:53Z |
| format | Article |
| id | doaj.art-1264cd3caa6f4c37828931d9b1d5e8d5 |
| institution | Directory Open Access Journal |
| issn | 2475-0379 |
| language | English |
| last_indexed | 2024-03-12T06:42:53Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj.art-1264cd3caa6f4c37828931d9b1d5e8d52023-09-03T00:48:08ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792020-07-014587988510.1002/rth2.12344Sex differences in flow cytometry–based platelet reactivity in stable outpatients suspected of myocardial ischemiaFarahnaz Waissi0Mirthe Dekker1Ingrid E.M. Bank2Suzanne J.A. Korporaal3Rolf T. Urbanus4Gert J. deBorst5Gerard Pasterkamp6Asbjorn M. Scholtens7Diederick E. Grobbee8Arend Mosterd9Dominique P.V. deKleijn10Leo Timmers11Department of Vascular Surgery University Medical Center Utrecht Utrecht The NetherlandsDepartment of Vascular Surgery University Medical Center Utrecht Utrecht The NetherlandsDepartment of CardiologyMeander Medical Center Amersfoort The NetherlandsLaboratory of Experimental Cardiology University Medical Center Utrecht Utrecht The NetherlandsDepartment of Clinical Chemistry and Hematology University Medical Center Utrecht Utrecht The NetherlandsDepartment of Vascular Surgery University Medical Center Utrecht Utrecht The NetherlandsLaboratory of Experimental Cardiology University Medical Center Utrecht Utrecht The NetherlandsDepartment of Nuclear MedicineMeander Medical Center Amersfoort The NetherlandsJulius Center for Health Sciences and Primary Care University Medical Center UtrechtUtrecht University Utrecht The NetherlandsDepartment of CardiologyMeander Medical Center Amersfoort The NetherlandsDepartment of Vascular Surgery University Medical Center Utrecht Utrecht The NetherlandsDepartment of Cardiology University Medical Center Utrecht Utrecht The NetherlandsAbstract Background Antiplatelet therapy is the mainstay of secondary prevention of cardiovascular events. Studies suggest that women do not obtain equal therapeutic benefit from antiplatelet therapy compared with men. The link between sex differences in platelet biology and response to antiplatelet therapies is unclear. We therefore investigated the role of sex differences in platelet reactivity in a cohort of outpatients with chest pain, in response to treatment with antiplatelet agents. Methods Platelet reactivity was measured in 382 randomly selected patients participating in the Myocardial Ischemia Detection by Circulating Biomarkers (MYOMARKER) study, an observational cohort study of outpatients suspected of myocardial ischemia. In all patients, blood was collected during diagnostic workup, and platelet reactivity was assessed with a flow cytometry–based platelet activation test that quantifies both platelet degranulation (P‐selectin expression) and platelet aggregation (fibrinogen binding to integrin αIIbβ3) in whole blood. Results Platelet reactivity was higher in women compared with men when activated with protease activating receptor 1–activating peptide SFLLRN (PAR1‐AP) and adenosine 5′‐phosphate (ADP), independent of age, basal activation status, estimated glomerular filtration rate < 60, platelet count, statin use, the use of P2Y12 inhibitors, or the use of aspirin. P2Y12 inhibitor use strongly reduced fibrinogen binding after stimulation with PAR1‐AP, but only slightly reduced platelet P‐selectin expression. Calculation of the relative inhibition in P2Y12 users indicated 62% inhibition of the response toward ADP. Stratified analysis showed that women (n = 14) using P2Y12 inhibitors showed less inhibition of fibrinogen binding after PAR1‐AP stimulation than men (n = 38) using P2Y12 inhibitors. Conclusions These findings call for further study of differential effects of P2Y12 inhibitors in women with suspected myocardial ischemia.https://doi.org/10.1002/rth2.12344antiplatelet therapyflow cytometryplateletplatelet activationsex differences |
| spellingShingle | Farahnaz Waissi Mirthe Dekker Ingrid E.M. Bank Suzanne J.A. Korporaal Rolf T. Urbanus Gert J. deBorst Gerard Pasterkamp Asbjorn M. Scholtens Diederick E. Grobbee Arend Mosterd Dominique P.V. deKleijn Leo Timmers Sex differences in flow cytometry–based platelet reactivity in stable outpatients suspected of myocardial ischemia Research and Practice in Thrombosis and Haemostasis antiplatelet therapy flow cytometry platelet platelet activation sex differences |
| title | Sex differences in flow cytometry–based platelet reactivity in stable outpatients suspected of myocardial ischemia |
| title_full | Sex differences in flow cytometry–based platelet reactivity in stable outpatients suspected of myocardial ischemia |
| title_fullStr | Sex differences in flow cytometry–based platelet reactivity in stable outpatients suspected of myocardial ischemia |
| title_full_unstemmed | Sex differences in flow cytometry–based platelet reactivity in stable outpatients suspected of myocardial ischemia |
| title_short | Sex differences in flow cytometry–based platelet reactivity in stable outpatients suspected of myocardial ischemia |
| title_sort | sex differences in flow cytometry based platelet reactivity in stable outpatients suspected of myocardial ischemia |
| topic | antiplatelet therapy flow cytometry platelet platelet activation sex differences |
| url | https://doi.org/10.1002/rth2.12344 |
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