{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:19:34Z","timestamp":1773289174042,"version":"3.50.1"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,12,27]],"date-time":"2018-12-27T00:00:00Z","timestamp":1545868800000},"content-version":"unspecified","delay-in-days":26,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microsc Microanal"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Venous thrombosis is associated with combined oral contraceptive (COC) use. We investigated the impact of two ethinyl estradiol (EE) and drospirenone (DRSP) containing COCs (3 mg DRSP\/20<jats:italic>\u00b5<\/jats:italic>g EE and 3<jats:italic>\u00b5<\/jats:italic>g DRSP\/30<jats:italic>\u00b5<\/jats:italic>g EE) on the viscoelasticity of whole blood clots along with the biophysical and biochemical characteristics of erythrocytes. Thromboelastography (TEG) analysis showed a tendency toward a hypercoagulable state in the COCs groups that was more pronounced with higher EE concentrations. Light microscopy and scanning electron microscopy (SEM) showed rouleaux formation of erythrocytes and alterations to the erythrocyte shape for both COC groups, which was attributed to membrane damage. SEM analysis showed spontaneous activation of fibrin and platelets in the COC groups, along with interactions between erythrocytes and platelets and\/or fibrin. Confocal microscopy confirmed compromised membrane integrity in the COC groups compared to controls. Global thrombosis test analysis showed increased platelet activation and low thrombolysis in both COC groups when compared to controls. In conclusion, DRSP\/EE formulations impact erythrocytes\u2019 biophysical and biochemical properties to cause a shift in hemostasis to a prothrombotic state. Although these effects are mostly subclinical the long-term effects and risks involved with the use of these hormones should be considered carefully for each individual.<\/jats:p>","DOI":"10.1017\/s1431927618015453","type":"journal-article","created":{"date-parts":[[2018,12,27]],"date-time":"2018-12-27T12:24:58Z","timestamp":1545913498000},"page":"713-728","source":"Crossref","is-referenced-by-count":8,"title":["The Impact of Two Combined Oral Contraceptives Containing Ethinyl Estradiol and Drospirenone on Whole Blood Clot Viscoelasticity and the Biophysical and Biochemical Characteristics of Erythrocytes"],"prefix":"10.1093","volume":"24","author":[{"given":"Odette","family":"Emmerson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janette","family":"Bester","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barend G.","family":"Lindeque","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5732-5007","authenticated-orcid":false,"given":"Albe C.","family":"Swanepoel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,12,27]]},"reference":[{"key":"S1431927618015453_ref67","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2014.02.018"},{"key":"S1431927618015453_ref65","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2006.02.006"},{"key":"S1431927618015453_ref64","first-page":"495","article-title":"Hormonal contraception\u2014what kind, when, and for whom?","volume":"108","author":"Wiegratz","year":"2011","journal-title":"Dtsch \u00c4rztebl Int"},{"key":"S1431927618015453_ref62","doi-asserted-by":"crossref","first-page":"883","DOI":"10.4103\/0366-6999.179783","article-title":"Comparison of drospirenone-with cyproterone acetate-containing oral contraceptives, combined with metformin and lifestyle modifications in women with polycystic ovary syndrome and metabolic disorders: A prospective randomized control trial","volume":"129","author":"Wang","year":"2016","journal-title":"Chin Med J"},{"key":"S1431927618015453_ref61","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000095974.95122.EC"},{"key":"S1431927618015453_ref19","unstructured":"US Food and Drug Administration (2015) FDA monograph on physician labelling for Yasmin 28 tablets (drospirenone and ethinyl estradiol). Physician labelling."},{"key":"S1431927618015453_ref59","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-2221"},{"key":"S1431927618015453_ref58","doi-asserted-by":"publisher","DOI":"10.1017\/S1431927616011478"},{"key":"S1431927618015453_ref68","doi-asserted-by":"publisher","DOI":"10.1097\/00001721-200301000-00007"},{"key":"S1431927618015453_ref55","doi-asserted-by":"publisher","DOI":"10.1017\/S1431927617000484"},{"key":"S1431927618015453_ref53","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.3.1548"},{"key":"S1431927618015453_ref51","doi-asserted-by":"publisher","DOI":"10.1159\/000342229"},{"key":"S1431927618015453_ref44","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.324.7342.869"},{"key":"S1431927618015453_ref43","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000279448.62221.a8"},{"key":"S1431927618015453_ref41","doi-asserted-by":"publisher","DOI":"10.1039\/C4IB00025K"},{"key":"S1431927618015453_ref40","doi-asserted-by":"publisher","DOI":"10.1159\/000447895"},{"key":"S1431927618015453_ref39","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2008.03.009"},{"key":"S1431927618015453_ref36","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2011.09.050"},{"key":"S1431927618015453_ref33","doi-asserted-by":"crossref","unstructured":"Mathur R , Levin O Azziz R (2008) Use of ethinylestradiol\/drospirenone combination in patients with the polycystic ovary syndrome. Ther Clin Risk Manag 4(2), 487\u2013492.","DOI":"10.2147\/TCRM.S6864"},{"key":"S1431927618015453_ref26","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2013-003401"},{"key":"S1431927618015453_ref23","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/13697130500148875","article-title":"Pharmacology of estrogens and progestogens: Influence of different routes of administration","volume":"8","author":"H","year":"2005","journal-title":"Climacteric"},{"key":"S1431927618015453_ref20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21625"},{"key":"S1431927618015453_ref18","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13109"},{"key":"S1431927618015453_ref60","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03455.x"},{"key":"S1431927618015453_ref17","doi-asserted-by":"publisher","DOI":"10.1186\/s12917-017-1278-y"},{"key":"S1431927618015453_ref16","unstructured":"Du VX , Huskens D , Maas C , Al Dieri R , de Groot PG de Laat B (2014) New insights into the role of erythrocytes in thrombus formation. Semin Thromb Hemost, 40(1), 72\u201380."},{"key":"S1431927618015453_ref15","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e31820095a2"},{"key":"S1431927618015453_ref47","doi-asserted-by":"publisher","DOI":"10.1080\/13697130500330382"},{"key":"S1431927618015453_ref14","doi-asserted-by":"publisher","DOI":"10.1177\/1076029610391652"},{"key":"S1431927618015453_ref13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1055\/s-0038-1642645","article-title":"Biochemical and molecular aspects of the coagulation cascade","volume":"74","author":"Davie","year":"1995","journal-title":"Thromb Haemost"},{"key":"S1431927618015453_ref12","doi-asserted-by":"publisher","DOI":"10.1002\/cnm.1274"},{"key":"S1431927618015453_ref11","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-12-25"},{"key":"S1431927618015453_ref9","doi-asserted-by":"publisher","DOI":"10.1177\/2042098614548857"},{"key":"S1431927618015453_ref8","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431X20154655"},{"key":"S1431927618015453_ref7","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(87)80129-1"},{"key":"S1431927618015453_ref4","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(00)76791-9"},{"key":"S1431927618015453_ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2014.03.017"},{"key":"S1431927618015453_ref1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.301607"},{"key":"S1431927618015453_ref66","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-08-2527"},{"key":"S1431927618015453_ref34","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-161166"},{"key":"S1431927618015453_ref27","doi-asserted-by":"crossref","unstructured":"Kaestner L Bogdanova A (2014) Regulation of Red Cell Life-Span, Erythropoiesis, Senescence and Clearance. Lausanne, Switzerland: Frontiers E-books.","DOI":"10.3389\/978-2-88919-348-6"},{"key":"S1431927618015453_ref38","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02373.x"},{"key":"S1431927618015453_ref35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1995.tb31386.x"},{"key":"S1431927618015453_ref31","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2005.09.015"},{"key":"S1431927618015453_ref10","first-page":"3","article-title":"The evolution of oral contraceptives: 40 years of continuous improvement","volume":"20","author":"Burkman","year":"2002","journal-title":"Clinician"},{"key":"S1431927618015453_ref6","doi-asserted-by":"crossref","unstructured":"Baskurt OK Meiselman HJ (2003) Blood rheology and hemodynamics. Semin Thromb Hemost, 29(5), 435\u2013450.","DOI":"10.1055\/s-2003-44551"},{"key":"S1431927618015453_ref37","doi-asserted-by":"publisher","DOI":"10.1016\/S1521-6934(03)00014-2"},{"key":"S1431927618015453_ref21","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-005-0020-x"},{"key":"S1431927618015453_ref52","doi-asserted-by":"publisher","DOI":"10.1136\/jfprhc-2011-100225"},{"key":"S1431927618015453_ref57","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2016.08.022"},{"key":"S1431927618015453_ref30","doi-asserted-by":"publisher","DOI":"10.1136\/jfprhc-2011-100214"},{"key":"S1431927618015453_ref56","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-015-0148-7"},{"key":"S1431927618015453_ref48","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-011-9182-4"},{"key":"S1431927618015453_ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.legalmed.2014.10.001"},{"key":"S1431927618015453_ref42","unstructured":"Reid R (2009) Oral contraceptives and venous thromboembolism, consensus opinion from an international workshop held in Berlin, Germany. December."},{"key":"S1431927618015453_ref24","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031281"},{"key":"S1431927618015453_ref63","doi-asserted-by":"publisher","DOI":"10.2147\/IJWH.S71906"},{"key":"S1431927618015453_ref32","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2012.03.001"},{"key":"S1431927618015453_ref28","first-page":"3050","article-title":"Venous thromboembolism and combined oral contraceptives. Reported adverse reactions indicate at least similar risk with the most recent contraceptive pills","volume":"100","author":"Kieler","year":"2003","journal-title":"Lakartidningen"},{"key":"S1431927618015453_ref50","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000385"},{"key":"S1431927618015453_ref49","unstructured":"Stegeman BHB (2013) Hormonal contraceptives and venous thrombosis. Department of Thrombosis and Hemostasis, Faculty of Medicine, Leiden University Library (LUMC), Leiden University, Leiden, Netherlands."},{"key":"S1431927618015453_ref45","unstructured":"Shin S , Ku Y , Babu N Singh M (2007) Erythrocyte deformability and its variation in diabetes mellitus. Indian J Exp Biol 45(1), 121\u2013128."},{"key":"S1431927618015453_ref46","first-page":"981","article-title":"Safety and efficacy of a new oral contraceptive containing drospirenone","volume":"47","author":"Shulman","year":"2002","journal-title":"J Reprod Med"},{"key":"S1431927618015453_ref54","doi-asserted-by":"publisher","DOI":"10.1017\/S1431927617000472"},{"key":"S1431927618015453_ref29","doi-asserted-by":"publisher","DOI":"10.1136\/jfprhc-2011-100213"},{"key":"S1431927618015453_ref5","doi-asserted-by":"crossref","unstructured":"Baskurt O , Neu B Meiselman HJ (2011) Red Blood Cell Aggregation. Boca Raton, Florida, USA: CRC Press.","DOI":"10.1201\/b11221"},{"key":"S1431927618015453_ref3","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.5.H1982"},{"key":"S1431927618015453_ref22","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.110463"}],"container-title":["Microscopy and Microanalysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1431927618015453","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T21:31:00Z","timestamp":1676410260000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mam\/article\/24\/6\/713\/6901482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12]]},"references-count":68,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["S1431927618015453"],"URL":"https:\/\/doi.org\/10.1017\/s1431927618015453","relation":{},"ISSN":["1431-9276","1435-8115"],"issn-type":[{"value":"1431-9276","type":"print"},{"value":"1435-8115","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12]]}}}