{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:09:59Z","timestamp":1789139399905,"version":"build-2803163510"},"reference-count":78,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T00:00:00Z","timestamp":1715385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cardiovascular diseases, among which includes coronary artery disease, represent one of the most important causes of mortality and morbidity worldwide. Research aimed at determining the risk factors involved recognizes a group of \u201ctraditional\u201d risk factors, but also more recent studies identified over 100 \u201cnovel\u201d ones which may have a role in the disease. Among the latter is the thrombophilia profile of a patient, a pathology well-established for its involvement in venous thromboembolism, but with less studied implications in arterial thrombosis. This paper reviews the literature, explaining the pathophysiology of the thrombophilia causes associated most with coronary thrombosis events. Results of several studies on the subject, including a meta-analysis with over 60,000 subjects, determined the significant involvement of factor V Leiden, prothrombin G20210A mutation, plasminogen activator inhibitor\u20131 and antiphospholipid syndrome in the development of coronary artery disease. The mechanisms involved are currently at different stages of research, with some already established and used as therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms25105228","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T08:03:08Z","timestamp":1715673788000},"page":"5228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Etiology of the Thrombotic Phenomena Involved in the Process of Coronary Artery Disease\u2014What Is the Role of Thrombophilic Genes in the Development of This Pathology?"],"prefix":"10.3390","volume":"25","author":[{"given":"Iris","family":"Bararu Bojan","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, University of Medicine and Pharmacy Gr. T. Popa, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Dobreanu","sequence":"additional","affiliation":[{"name":"Recuperare Hospital Iasi, University of Medicine and Pharmacy Gr. T. Popa, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Vladeanu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Medicine and Pharmacy Gr. T. Popa, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9240-2175","authenticated-orcid":false,"given":"Manuela","family":"Ciocoiu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Medicine and Pharmacy Gr. T. Popa, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8942-1909","authenticated-orcid":false,"given":"Codruta","family":"Badescu","sequence":"additional","affiliation":[{"name":"Recuperare Hospital Iasi, University of Medicine and Pharmacy Gr. T. Popa, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5448-7761","authenticated-orcid":false,"given":"Carmen","family":"Plesoianu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Medicine and Pharmacy Gr. T. Popa, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0949-7538","authenticated-orcid":false,"given":"Nina","family":"Filip","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Medicine and Pharmacy Gr. T. Popa, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Iliescu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Medicine and Pharmacy Gr. T. Popa, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5836-1517","authenticated-orcid":false,"given":"Otilia","family":"Frasinariu","sequence":"additional","affiliation":[{"name":"Department of Pediatry, University of Medicine and Pharmacy Gr. T. Popa, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Bojan","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, University of Medicine and Pharmacy Gr. T. Popa, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razvan","family":"Tudor","sequence":"additional","affiliation":[{"name":"Department of Orthopedy, University of Medicine and Pharmacy Gr. T. Popa, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7050-8430","authenticated-orcid":false,"given":"Oana Viola","family":"Badulescu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Medicine and Pharmacy Gr. T. Popa, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,11]]},"reference":[{"key":"ref_1","unstructured":"(2023, October 15). Cardiovascular Diseases. Available online: https:\/\/www.who.int\/health-topics\/cardiovascular-diseases#tab=tab_1."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1477-9560-10-12","article-title":"Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment","volume":"10","author":"Bratseth","year":"2012","journal-title":"Thromb. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"169","DOI":"10.2991\/jegh.k.201217.001","article-title":"Epidemiology and the Magnitude of Coronary Artery Disease and Acute Coronary Syndrome: A Narrative Review","volume":"11","author":"Ralapanawa","year":"2021","journal-title":"J. Epidemiol. Glob. Health."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1159\/000066407","article-title":"Hematological risk factors for coronary heart disease","volume":"11","year":"2002","journal-title":"Med. Princ. Pract."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/S0140-6736(13)61752-3","article-title":"The Framingham Heart Study and the epidemiology of cardiovascular disease: A historical perspective","volume":"383","author":"Mahmood","year":"2014","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"59","DOI":"10.4081\/jphr.2012.e11","article-title":"Novel risk factors of cardiovascular disease and their associations between obesity, physical activity and physical fitness","volume":"1","author":"Buchan","year":"2012","journal-title":"J. Public Health Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"ehaa946.1553","DOI":"10.1093\/ehjci\/ehaa946.1553","article-title":"Acute coronary syndrome and thrombophilia in young patients:clinical data, experience","volume":"41","author":"Stoykova","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4103\/HEARTVIEWS.HEARTVIEWS_106_17","article-title":"Risk Factors for Coronary Artery Disease: Historical Perspectives","volume":"18","author":"Hajar","year":"2017","journal-title":"Hear. Views"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e057930","DOI":"10.1136\/bmjopen-2021-057930","article-title":"Modifiable cardiovascular disease risk factors among adults in southern Ethiopia: A community-based cross-sectional study","volume":"12","author":"Kumma","year":"2022","journal-title":"BMJ Open"},{"key":"ref_10","first-page":"293","article-title":"Emerging modifiable risk factors for cardiovascular disease in women: Obesity, physical activity, and sedentary behavior","volume":"40","author":"Barnes","year":"2013","journal-title":"Tex. Heart Inst. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1007\/s11239-014-1166-2","article-title":"Thrombophilic state in young patients with acute myocardial infarction","volume":"39","author":"Maor","year":"2015","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.hlc.2020.05.108","article-title":"Cardiovascular Disease in Women: From Pathophysiology to Novel and Emerging Risk Factors","volume":"30","author":"Geraghty","year":"2021","journal-title":"Heart Lung Circ."},{"key":"ref_13","unstructured":"Brown, J.C., Gerhardt, T.E., and Kwon, E. (2023, October 15). Risk Factors for Coronary Artery Disease. [Updated 2021 Jun 5], StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK554410\/."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1161\/01.STR.32.8.1793","article-title":"Inherited thrombophilia in ischemic stroke and its pathogenic subtypes","volume":"32","author":"Hankey","year":"2001","journal-title":"Stroke"},{"key":"ref_15","first-page":"13","article-title":"Thrombophilia in coronary artery disease: A double jeopardy","volume":"120","author":"Mohanty","year":"2004","journal-title":"Indian. J. Med. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1053\/j.seminhematol.2007.01.008","article-title":"Inherited thrombophilia in arterial disease: A selective review","volume":"44","author":"Boehlen","year":"2007","journal-title":"Semin. Hematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1177\/145749691210100204","article-title":"Role and management of coagulation disorders in peripheral arterial disease","volume":"101","author":"Lassila","year":"2012","journal-title":"Scand. J. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1177\/1076029617703481","article-title":"Thrombophilia in 153 Patients with Premature Cardiovascular Disease \u2264 Age 45","volume":"24","author":"Milgrom","year":"2018","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/S0002-8703(03)00519-2","article-title":"Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: A meta-analysis of published studies","volume":"146","author":"Kim","year":"2003","journal-title":"Am. Heart J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1385\/CRIAI:25:1:79","article-title":"Atherosclerosis and antiphospholipid syndrome","volume":"25","author":"Jara","year":"2003","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1007\/s12016-007-0008-9","article-title":"Systemic antiphospholipid syndrome and atherosclerosis","volume":"32","author":"Jara","year":"2007","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_22","first-page":"270","article-title":"Hyperhomocysteinemia and hypercoagulable state in carotid plaque evolution. Novel risk factors or coincidental risk predictors?","volume":"26","author":"Pitoulias","year":"2007","journal-title":"Int. Angiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1111\/j.1538-7836.2009.03308.x","article-title":"Atherosclerosis in thrombotic primary antiphospholipid syndrome","volume":"7","author":"Ames","year":"2009","journal-title":"J. Thromb. Haemost."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Peng, X., Zhou, Y., Wu, X., Wang, X., Bai, H., Li, Y., Wang, Z., Chen, X., and Wang, Y. (2020). Association of methylenetetrahydrofolate reductase (MTHFR) variant C677T and risk of carotid atherosclerosis: A cross-sectional analysis of 730 Chinese Han adults in Chongqing. BMC Cardiovasc. Disord, 20.","DOI":"10.1186\/s12872-020-01505-1"},{"key":"ref_25","first-page":"359","article-title":"Prevalence of thrombophilia in asymptomatic individuals with a family history of thrombosis","volume":"17","author":"Vagdatli","year":"2013","journal-title":"Hippokratia"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Khider, L., Gendron, N., and Mauge, L. (2022). Inherited Thrombophilia in the Era of Direct Oral Anticoagulants. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031821"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.jstrokecerebrovasdis.2018.12.006","article-title":"Clinical Impact of Thrombophilia Screening in Young Adults with Ischemic Stroke","volume":"28","author":"Omran","year":"2019","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"515","DOI":"10.4103\/0019-5049.144643","article-title":"Overview of the coagulation system","volume":"58","author":"Palta","year":"2014","journal-title":"Indian. J. Anaesth."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1161\/01.ATV.0000130465.23430.74","article-title":"Role of tissue factor in hemostasis, thrombosis, and vascular development","volume":"24","author":"Mackman","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.1161\/hc2501.092492","article-title":"Deficiency of tissue factor pathway inhibitor promotes atherosclerosis and thrombosis in mice","volume":"103","author":"Westrick","year":"2001","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1160\/TH15-02-0141","article-title":"Classic thrombophilic gene variants","volume":"114","author":"Mannucci","year":"2015","journal-title":"Thromb. Haemost."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1177\/1076029617744320","article-title":"Association of FV G1691A Polymorphism but not A4070G With Coronary Artery Disease","volume":"24","author":"Amara","year":"2018","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1093\/cvr\/cvp066","article-title":"Is thrombin a key player in the \u2018coagulation-atherogenesis\u2019 maze?","volume":"82","author":"Borissoff","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s11239-013-1026-5","article-title":"Thrombin generation and atherosclerosis","volume":"37","author":"Kalz","year":"2014","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4757","DOI":"10.1002\/jcb.27771","article-title":"Role of thrombin in the pathogenesis of atherosclerosis","volume":"120","author":"Jaberi","year":"2019","journal-title":"J. Cell Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e003553","DOI":"10.1161\/JAHA.116.003553","article-title":"Thrombin Generation and Atherothrombosis: What Does the Evidence Indicate?","volume":"5","author":"Hemker","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Borissoff, J.I., Otten, J.J., Heeneman, S., Leenders, P., van Oerle, R., Soehnlein, O., Loubele, S.T., Hamuly\u00e1k, K., Hackeng, T.M., and Daemen, M.J. (2013). Genetic and pharmacological modifications of thrombin formation in apolipoprotein e-deficient mice determine atherosclerosis severity and atherothrombosis onset in a neutrophil-dependent manner. PLoS ONE., 8.","DOI":"10.1371\/journal.pone.0055784"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/S0140-6736(06)68263-9","article-title":"Seven haemostatic gene polymorphisms in coronary disease: Meta-analysis of 66,155 cases and 91,307 controls","volume":"367","author":"Ye","year":"2006","journal-title":"Lancet"},{"key":"ref_39","unstructured":"Albagoush, S.A., Koya, S., Chakraborty, R.K., and Schmidt, A.E. (2022). StatPearls [Internet], StatPearls Publishing."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1038\/s41588-019-0519-3","article-title":"Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease","volume":"51","author":"Klarin","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1055\/s-2007-996025","article-title":"Epidemiology of factor V Leiden: Clinical implications","volume":"24","author":"Chiusolo","year":"1998","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_42","unstructured":"Lam, W., and Moosavi, L. (2022). StatPearls [Internet], StatPearls Publishing."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"47","DOI":"10.4103\/0973-6247.95053","article-title":"Mechanism and pathophysiology of activated protein C-related factor V leiden in venous thrombosis","volume":"6","author":"Yusuf","year":"2012","journal-title":"Asian J. Transfus. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1055\/s-2003-38331","article-title":"Congenital and acquired activated protein C resistance","volume":"3","author":"Nicolaes","year":"2003","journal-title":"Semin. Vasc. Med."},{"key":"ref_45","first-page":"622","article-title":"Antiphospholipid antibody profiles and their clinical associations in Chinese patients with systemic lupus erythematosus","volume":"32","author":"Mok","year":"2005","journal-title":"J. Rheumatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1055\/s-0037-1616136","article-title":"Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism-pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Study Group for Pooled-Analysis in Venous Thromboembolism","volume":"86","author":"Emmerich","year":"2001","journal-title":"Thromb. Haemost."},{"key":"ref_47","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., and Amemiya, A. (2006). GeneReviews\u00ae [Internet], University of Washington."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e2011054","DOI":"10.4084\/mjhid.2011.054","article-title":"Epidemiology of Prothrombin G20210A Mutation in the Mediterranean Region","volume":"3","author":"Jadaon","year":"2011","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1161\/01.CIR.0000135582.53444.87","article-title":"Cardiology patient pages. Prothrombin 20210 mutation (factor II mutation)","volume":"110","author":"Varga","year":"2004","journal-title":"Circulation"},{"key":"ref_50","unstructured":"Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (2011). Recommendations from the EGAPP Working Group: Routine testing for Factor V Leiden (R506Q) and prothrombin (20210G>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members. Genet. Med., 13, 67\u201376."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1007\/s11033-010-0370-1","article-title":"Varied association of prothrombin G20210A polymorphism with coronary artery disease susceptibility in different ethnic groups: Evidence from 15,041 cases and 21,507 controls","volume":"38","author":"Jin","year":"2011","journal-title":"Mol. Biol. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1161\/01.ATV.0000242905.41404.68","article-title":"PAI-1 and the metabolic syndrome: Links, causes, and consequences","volume":"26","author":"Alessi","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1161\/STROKEAHA.111.622217","article-title":"Plasminogen activator inhibitor-1 and thrombotic cerebrovascular diseases","volume":"43","author":"Brogren","year":"2012","journal-title":"Stroke"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1111\/j.1538-7836.2005.01420.x","article-title":"PAI-1 and atherothrombosis","volume":"3","author":"Vaughan","year":"2005","journal-title":"J. Thromb. Haemost."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"622473","DOI":"10.3389\/fcvm.2020.622473","article-title":"Targeting PAI-1 in Cardiovascular Disease: Structural Insights Into PAI-1 Functionality and Inhibition","volume":"7","author":"Sillen","year":"2020","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1007\/s12272-018-1016-4","article-title":"Causes of hyperhomocysteinemia and its pathological significance","volume":"41","author":"Kim","year":"2018","journal-title":"Arch. Pharm. Res."},{"key":"ref_57","unstructured":"Leclerc, D., Sibani, S., and Rozen, R. (2000). Madame Curie Bioscience Database [Internet], Landes Bioscience."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev.nutr.19.1.217","article-title":"Homocysteine metabolism","volume":"19","author":"Selhub","year":"1999","journal-title":"Annu. Rev. Nutr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.numecd.2004.05.003","article-title":"Role of vitamins B6, B12 and folic acid on hyperhomocysteinemia in a Pakistani population of patients with acute myocardial infarction","volume":"15","author":"Iqbal","year":"2005","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1161\/CIRCULATIONAHA.108.778837","article-title":"Hypercoagulable states in cardiovascular disease","volume":"118","author":"Chan","year":"2008","journal-title":"Circulation"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1056\/NEJMoa060900","article-title":"Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease","volume":"354","author":"Lonn","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_62","unstructured":"Bustamante, J.G., Goyal, A., and Singhal, M. (2022). StatPearls [Internet], StatPearls Publishing."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s13317-011-0017-9","article-title":"Pathophysiology of the antiphospholipid antibody syndrome","volume":"2","author":"Willis","year":"2011","journal-title":"Auto. Immun. Highlights"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e13613","DOI":"10.1097\/MD.0000000000013613","article-title":"Antiphospholipid syndrome combined with acute coronary syndrome: Case report","volume":"97","author":"Shan","year":"2018","journal-title":"Medicine"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1536\/ihj.46.631","article-title":"Association between anticardiolipin antibodies and recurrent cardiac events in patients with acute coronary syndrome","volume":"46","author":"Pamir","year":"2005","journal-title":"Int. Heart J."},{"key":"ref_66","unstructured":"(2023, October 15). Overview of the Treatment of Lower Extremity Deep Vein Thrombosis (DVT). Available online: https:\/\/www.uptodate.com\/contents\/overview-of-the-treatment-of-lower-extremity-deep-vein-thrombosis-dvt."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1007\/s11239-020-02090-y","article-title":"Thrombophilia screening revisited: An issue of personalized medicine","volume":"49","author":"Colucci","year":"2020","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1001\/jama.2020.17272","article-title":"Diagnosis and Treatment of Lower Extremity Venous Thromboembolism: A Review","volume":"324","author":"Chopard","year":"2020","journal-title":"JAMA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1056\/NEJMra1700365","article-title":"Thrombophilia Testing and Venous Thrombosis","volume":"377","author":"Connors","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1159\/000073595","article-title":"Unusual forms of venous thrombosis and thrombophilia","volume":"32","author":"Martinelli","year":"2002","journal-title":"Pathophysiol. Haemost. Thromb."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1136\/pgmj.2006.048090","article-title":"Testing for thrombophilia: An evidence-based approach","volume":"82","author":"Merriman","year":"2006","journal-title":"Postgrad. Med. J."},{"key":"ref_72","unstructured":"(2023, October 15). ASH Draft Recommendations for Thrombophilia Testing. Available online: https:\/\/www.hematology.org\/-\/media\/hematology\/files\/education\/clinicians\/guidelines-quality\/documents\/thrombopilia-public-comment-supplementary-file.pdf?la=en&hash=E092A825084F5B5C36E08190929397D3."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e487","DOI":"10.7861\/clinmed.2020-1008","article-title":"Thrombophilia testing in the era of direct oral anticoagulants","volume":"21","author":"Darlow","year":"2021","journal-title":"Clin. Med."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Vaz, C., Bischoff, F., Monteiro, F., Lopes, M., Vasconcelos, F., Bastos, P., Tavares, G., Ferreira, M., Amorim, A., and Koch, C. (2018). Genetic Testing for Inherited Thrombophilia: 20 Years of Experience in a University and Tertiary Care Centre. Proceedings, 2.","DOI":"10.3390\/proceedings2090527"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1111\/jth.14008","article-title":"Novel assay demonstrates that coronary artery disease patients have heightened procoagulant platelet response","volume":"16","author":"Pasalic","year":"2018","journal-title":"J. Thromb. Haemost."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1076029620964590","DOI":"10.1177\/1076029620964590","article-title":"Prospective Assessment of Biomarkers of Hypercoagulability for the Identification of Patients with Severe Coronary Artery Disease. The ROADMAP-CAD Study","volume":"26","author":"Gerotziafas","year":"2020","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Badulescu, O.V., Sirbu, P.D., Filip, N., Bordeianu, G., Cojocaru, E., Budacu, C.C., Badescu, M.C., Bararu-Bojan, I., Veliceasa, B., and Ciocoiu, M. (2022). Hereditary Thrombophilia in the Era of COVID-19. Healthcare, 10.","DOI":"10.3390\/healthcare10060993"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"995","DOI":"10.3892\/etm.2021.10427","article-title":"Orthopedic surgery in hemophilic patients with musculoskeletal disorders: A systematic review","volume":"22","author":"Badulescu","year":"2021","journal-title":"Exp. Ther. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:44:04Z","timestamp":1760107444000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,11]]},"references-count":78,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25105228"],"URL":"https:\/\/doi.org\/10.3390\/ijms25105228","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,11]]}}}