{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T16:54:38Z","timestamp":1755795278210,"version":"3.44.0"},"reference-count":27,"publisher":"BMJ","issue":"2","funder":[{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009250","name":"National Institute for Social Care and Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009250","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Open Heart"],"accepted":{"date-parts":[[2017,4,4]]},"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Coronary artery disease (CAD) is associated with an increased prothrombotic tendency and is also linked to unfavourably altered clot microstructure. We have previously described a biomarker of clot microstructure (d<jats:sub>f<\/jats:sub>) that is unfavourably altered in acute myocardial infarction. The d<jats:sub>f<\/jats:sub> biomarker assesses whether the blood will form denser or looser microstructures when it clots. In this study we assessed in patients with stable chest pain whether d<jats:sub>f<\/jats:sub> can differentiate between obstructed and unobstructed CAD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A blood sample prior to angiography was obtained from 251 consecutive patients undergoing diagnostic coronary angiography. Patients were categorised based on angiographic findings as presence or absence of obstructive CAD (stenosis \u226550%). The blood sample was assessed using the d<jats:sub>f<\/jats:sub> biomarker, standard laboratory markers and platelet aggregometry (Multiplate).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A significant difference (p=0.028) in d<jats:sub>f<\/jats:sub> was observed between obstructive CAD (1.748\u00b10.057, n=83) and unobstructive CAD (1.732\u00b10.052, n=168), where patients with significant CAD produce denser, more tightly packed clots. d<jats:sub>f<\/jats:sub> was also raised in men with obstructive CAD compared with women (1.745\u00b10.055 vs 1.723\u00b10.052, p=0.007). Additionally d<jats:sub>f<\/jats:sub> significantly correlated with the platelets response to arachidonic acid as measured by the ASPItest area under the curve readings from platelet aggregometry (correlation coefficient=0.166, p=0.008), a low value of the ASPItest indicating effective aspirin use was associated with looser, less dense clots.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>For the first time, we characterise clot microstructure, as measured by d<jats:sub>f<\/jats:sub>, in patients with stable CAD. d<jats:sub>f<\/jats:sub> can potentially be used to risk-stratify patients with stable CAD and assess the efficacy of therapeutic interventions by measuring changes in clot microstructure.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/openhrt-2016-000562","type":"journal-article","created":{"date-parts":[[2017,6,24]],"date-time":"2017-06-24T20:10:09Z","timestamp":1498335009000},"page":"e000562","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Characterisation of clot microstructure properties in stable coronary artery disease"],"prefix":"10.1136","volume":"4","author":[{"given":"Ahmed","family":"Sabra","sequence":"first","affiliation":[{"name":"NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, UK"},{"name":"NISCHR Haemostasis Biomedical Research Unit, College of Medicine, Swansea University, Swansea, UK"},{"name":"Department of Cardiology, Princess of Wales Hospital, ABMU Health Board, Bridgend, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew James","family":"Lawrence","sequence":"additional","affiliation":[{"name":"NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, UK"},{"name":"NISCHR Haemostasis Biomedical Research Unit, College of Medicine, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Aubrey","sequence":"additional","affiliation":[{"name":"NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Obaid","sequence":"additional","affiliation":[{"name":"Cardiac Centre, Morriston Hospital, ABMU Health Board, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Chase","sequence":"additional","affiliation":[{"name":"Cardiac Centre, Morriston Hospital, ABMU Health Board, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dave","family":"Smith","sequence":"additional","affiliation":[{"name":"Cardiac Centre, Morriston Hospital, ABMU Health Board, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip","family":"Thomas","sequence":"additional","affiliation":[{"name":"Cardiac Centre, Morriston Hospital, ABMU Health Board, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Storton","sequence":"additional","affiliation":[{"name":"NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, UK"},{"name":"NISCHR Haemostasis Biomedical Research Unit, College of Medicine, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth R","family":"Davies","sequence":"additional","affiliation":[{"name":"NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, UK"},{"name":"NISCHR Haemostasis Biomedical Research Unit, College of Medicine, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Hawkins","sequence":"additional","affiliation":[{"name":"NISCHR Haemostasis Biomedical Research Unit, College of Medicine, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phylip Rhodri","family":"Williams","sequence":"additional","affiliation":[{"name":"College of Engineering, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith","family":"Morris","sequence":"additional","affiliation":[{"name":"School of Applied Science, Cardiff Metropolitan University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip Adrian","family":"Evans","sequence":"additional","affiliation":[{"name":"NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, UK"},{"name":"NISCHR Haemostasis Biomedical Research Unit, College of Medicine, Swansea University, Swansea, UK"},{"name":"Department of Emergency Medicine, Morriston Hospital, ABMU Health Board, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2017,6,23]]},"reference":[{"key":"2025081710181187000_4.2.e000562.1","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/j.1538-7836.2005.01705.x","article-title":"C-reactive protein contributes to the hypercoagulable state in coronary artery disease","volume":"4","author":"Song","year":"2006","journal-title":"J Thromb Haemost"},{"key":"2025081710181187000_4.2.e000562.2","doi-asserted-by":"crossref","first-page":"360","DOI":"10.3109\/09537100903548903","article-title":"Hypercoagulability, platelet function, inflammation and coronary artery disease acuity: results of the thrombotic RIsk progression (TRIP) study","volume":"21","author":"Tantry","year":"2010","journal-title":"Platelets"},{"key":"2025081710181187000_4.2.e000562.3","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.thromres.2013.03.015","article-title":"Detection of hypofibrinolysis in stable coronary artery disease using the overall haemostatic potential assay","volume":"131","author":"Reddel","year":"2013","journal-title":"Thromb Res"},{"key":"2025081710181187000_4.2.e000562.4","doi-asserted-by":"publisher","DOI":"10.1186\/1477-9560-10-12"},{"key":"2025081710181187000_4.2.e000562.5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-306639"},{"key":"2025081710181187000_4.2.e000562.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2004.07.029"},{"key":"2025081710181187000_4.2.e000562.7","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.20.5.1354"},{"key":"2025081710181187000_4.2.e000562.8","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000033221.73082.06"},{"key":"2025081710181187000_4.2.e000562.9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-269324"},{"key":"2025081710181187000_4.2.e000562.10","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1160\/TH15-04-0357","article-title":"Fractal dimension (df) as a new structural biomarker of clot microstructure in different stages of lung cancer","volume":"114","author":"Davies","year":"2015","journal-title":"Thromb Haemost"},{"key":"2025081710181187000_4.2.e000562.11","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s12883-015-0289-1","article-title":"The changes in clot microstructure in patients with ischaemic stroke and the effects of therapeutic intervention: a prospective observational study","volume":"15","author":"Stanford","year":"2015","journal-title":"BMC Neurol"},{"key":"2025081710181187000_4.2.e000562.12","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1111\/bjh.13173","article-title":"A new biomarker quantifies differences in clot microstructure in patients with venous thromboembolism","volume":"168","author":"Lawrence","year":"2015","journal-title":"Br J Haematol"},{"key":"2025081710181187000_4.2.e000562.13","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1007\/s00134-016-4496-z","article-title":"The effect of Sepsis and its inflammatory response on mechanical clot characteristics: a prospective observational study","volume":"42","author":"Davies","year":"2016","journal-title":"Intensive Care Med"},{"key":"2025081710181187000_4.2.e000562.14","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.atherosclerosis.2015.04.012","article-title":"Fractal dimension: a novel clot microstructure biomarker use in ST elevation myocardial infarction patients","volume":"240","author":"Lawrence","year":"2015","journal-title":"Atherosclerosis"},{"key":"2025081710181187000_4.2.e000562.15","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.thromres.2014.05.039","article-title":"A new structural biomarker that quantifies and predicts changes in clot strength and quality in a model of progressive haemodilution","volume":"134","author":"Lawrence","year":"2014","journal-title":"Thromb Res"},{"key":"2025081710181187000_4.2.e000562.16","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1080\/AC.67.4.2170686","article-title":"The prevalence and factors associated with aspirin resistance in patients premedicated with aspirin","volume":"67","author":"Al-Azzam","year":"2012","journal-title":"Acta Cardiol"},{"key":"2025081710181187000_4.2.e000562.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.11.030"},{"key":"2025081710181187000_4.2.e000562.18","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.chaos.2012.04.004","article-title":"Fractal discrimination of random fractal aggregates and its application in biomarker analysis for blood coagulation","volume":"45","author":"Brown","year":"2012","journal-title":"Chaos, Solitons & Fractals"},{"key":"2025081710181187000_4.2.e000562.19","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.jnnfm.2011.04.016","article-title":"Rheometrical and molecular dynamics simulation studies of incipient clot formation in fibrin-thrombin gels: an activation limited aggregation approach","volume":"166","author":"Curtis","year":"2011","journal-title":"J Nonnewton Fluid Mech"},{"key":"2025081710181187000_4.2.e000562.20","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.778837"},{"key":"2025081710181187000_4.2.e000562.21","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000350"},{"key":"2025081710181187000_4.2.e000562.22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.2006.00302.x"},{"key":"2025081710181187000_4.2.e000562.23","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1177\/1358863X9700200207","article-title":"Fibrinogen and cardiovascular risk","volume":"2","author":"Ernst","year":"1997","journal-title":"Vasc Med"},{"key":"2025081710181187000_4.2.e000562.24","first-page":"431","article-title":"Statins for primary cardiovascular prevention in the elderly","volume":"12","author":"Pedro-Botet","year":"2015","journal-title":"J Geriatr Cardiol"},{"key":"2025081710181187000_4.2.e000562.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.02.025"},{"key":"2025081710181187000_4.2.e000562.26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.01882.x"},{"key":"2025081710181187000_4.2.e000562.27","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0b013e32835d5458"}],"container-title":["Open Heart"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/openhrt-2016-000562","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T17:18:18Z","timestamp":1755451098000},"score":1,"resource":{"primary":{"URL":"https:\/\/openheart.bmj.com\/lookup\/doi\/10.1136\/openhrt-2016-000562"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6]]},"references-count":27,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2017,6,23]]},"published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1136\/openhrt-2016-000562"],"URL":"https:\/\/doi.org\/10.1136\/openhrt-2016-000562","relation":{},"ISSN":["2053-3624"],"issn-type":[{"type":"electronic","value":"2053-3624"}],"subject":[],"published":{"date-parts":[[2017,6]]}}}