{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T03:09:26Z","timestamp":1761102566017,"version":"build-2065373602"},"reference-count":97,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Reports"],"abstract":"<jats:p>Background and Clinical Significance: Arterial and venous thromboses are typically distinct clinical entities, each governed by unique pathophysiological mechanisms. The concurrent manifestation of both, particularly in the setting of massive pulmonary embolism (PE), is exceptionally rare and poses significant diagnostic and therapeutic challenges. Case Presentation: This report describes a 61-year-old male with well-controlled hypertension and type 2 diabetes who developed extensive thromboses involving deep vein thrombosis (DVT) of the right popliteal vein, arterial thrombosis of the left iliac artery, and massive PE. The patient was initially managed conservatively, in accordance with the European Society of Cardiology (ESC) 2019 Guidelines for Acute PE, using unfractionated heparin (UFH), low-molecular-weight heparin, a direct oral anticoagulant (DOAC), and adjunctive therapy. This approach was chosen due to the absence of hemodynamic instability. However, given failed percutaneous revascularization and persistent arterial occlusion, surgical thromboendarterectomy (TEA) was ultimately required. Post hoc genetic testing was prompted by the complex presentation in the absence of classical provoking factors\u2014such as trauma, surgery, malignancy, or antiphospholipid syndrome\u2014consistent with recommendations for selective thrombophilia testing in atypical or severe cases. The analysis revealed four thrombophilia-associated polymorphisms: heterozygous Factor V Leiden (FVL; R506Q genotype), Plasminogen Activator Inhibitor-1 (PAI-1; 4G\/5G genotype), Methylenetetrahydrofolate reductase (MTHFR; c.677C &gt; T genotype), and homozygous Angiotensin-Converting Enzyme Insertion\/Deletion (ACE I\/D; DD genotype). Conclusions: While each variant has been individually associated with thrombotic risk, their co-occurrence in a single patient with simultaneous arterial and venous thromboses has not, to our knowledge, been previously documented. This case underscores the potential for gene\u2013gene interactions to amplify thrombotic risk, even in the presence of variants traditionally considered to confer only modest to moderate risk. It highlights the need for a multidisciplinary approach and raises questions regarding pharmacogenetics, anticoagulation, and future research into cumulative genetic risk in complex thrombotic phenotypes.<\/jats:p>","DOI":"10.3390\/reports8030167","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T13:27:44Z","timestamp":1756733264000},"page":"167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Sole Case of Concurrent Arterial and Venous Thromboses with Massive Pulmonary Embolism and Carriage of Four Genetic Polymorphisms: Factor V Leiden, PAI-1 4G\/5G, MTHFR C677T, and ACE I\/D\u2014A Case Report"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4213-8142","authenticated-orcid":false,"given":"Nevena","family":"Ivanova","sequence":"first","affiliation":[{"name":"Department of Urology and General Medicine, Faculty of Medicine, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria"},{"name":"St Karidad MHAT, Karidad Medical Health Center, Cardiology, 4004 Plovdiv, Bulgaria"},{"name":"Department of Internal Diseases, Social Medicine, Physiotherapy and Rehabilitation, Disaster Medicine, Faculty of Medicine, University \u201cProf. Dr. Asen Zlatarov\u201d, 8010 Burgas, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1016\/S0735-1097(23)03580-5","article-title":"Simultaneous arterial and venous thromboembolism","volume":"81","author":"Park","year":"2023","journal-title":"J. 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