{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T14:32:45Z","timestamp":1754145165084,"version":"3.41.2"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec018\">\n<jats:title>Background<\/jats:title>\n<jats:p>Clonal hematopoiesis of indeterminate potential (CHIP) is a novel risk factor for thromboembolic events. While CHIP is linked to an increased risk of incident atherothrombosis (ATE), the link between these two conditions varies across studies. Furthermore, the association between CHIP and incident venous thromboembolism (VTE) has not yet been well characterized. Among patients with established ATE and VTE, it is still unclear how CHIP carriership influences their health outcomes. We aim to conduct a systematic review and meta-analysis to: i) determine the impact of CHIP carriership on incident ATE and VTE; and ii) evaluate the prevalence and clinical consequences of CHIP mutations among individuals with established ATE or VTE.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec019\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We will search MEDLINE, EMBASE, Scopus and CINAHL for randomized trials, cohort studies, or case control studies reporting thromboembolic events among adult CHIP carriers and non-carriers in two populations: i) individuals without prior ATE (coronary artery disease, myocardial infarction, ischemic stroke, peripheral arterial disease) or VTE (pulmonary embolism, deep vein thrombosis, superficial vein thrombosis); and ii) individuals with established ATE or VTE. Cross-sectional studies will be included to determine the prevalence of CHIP among individuals with established thromboembolic disease. The primary outcome will be incident ATE and VTE. Secondary outcomes will be: i) CHIP prevalence among individuals with established ATE or VTE; and ii) recurrent thromboembolism and treatment-associated bleeding among individuals with established ATE or VTE. We will use random-effects meta-analyses, with subgroup analyses by participant demographics, ATE and VTE risk factors, and CHIP-specific characteristics.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec020\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>By understanding the prognostic impact of CHIP carriership, our findings will inform future research on CHIP\u2019s role as a predictive biomarker for ATE and VTE in the general population and among individuals with established thromboembolic disease.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec021\">\n<jats:title>Registration<\/jats:title>\n<jats:p>This systematic review protocol was registered with the Internal Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42024539923).<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0328650","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T17:30:59Z","timestamp":1752687059000},"page":"e0328650","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of clonal hematopoiesis of indeterminate potential on arterial atherothrombosis and venous thromboembolism: Protocol for a systematic review and meta-analysis"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8530-5242","authenticated-orcid":true,"given":"Angela","family":"Todorovski","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2407-9000","authenticated-orcid":true,"given":"Tzu-Fei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0599-6690","authenticated-orcid":true,"given":"Evan","family":"Sterling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Collins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8296-2972","authenticated-orcid":true,"given":"Marc","family":"Carrier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Siegal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha","family":"Kekre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy","family":"Khalif\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7429-4724","authenticated-orcid":true,"given":"Yan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"issue":"9828","key":"pone.0328650.ref001","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1016\/S0140-6736(11)61904-1","article-title":"Pulmonary embolism and deep vein thrombosis","volume":"379","author":"SZ Goldhaber","year":"2012","journal-title":"Lancet"},{"key":"pone.0328650.ref002","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1056\/NEJMoa1701719","article-title":"Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease","volume":"377","author":"S Jaiswal","year":"2017","journal-title":"N Engl J Med"},{"issue":"3","key":"pone.0328650.ref003","article-title":"Is hematopoietic clonality of indetermined potential a risk factor for pulmonary embolism?","volume":"5","author":"S Soudet","year":"2021","journal-title":"TH Open"},{"key":"pone.0328650.ref004","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1182\/blood-2023-180764","article-title":"Clonal Hematopoiesis and venous thromboembolism in the UK Biobank","volume":"142","author":"B Zon","year":"2023","journal-title":"Blood"},{"key":"pone.0328650.ref005","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.yjmcc.2021.07.004","article-title":"Clonal hematopoiesis of indeterminate potential (CHIP): linking somatic mutations, hematopoiesis, chronic inflammation and cardiovascular disease","volume":"161","author":"CS Marnell","year":"2021","journal-title":"J Mol Cell Cardiol"},{"issue":"7939","key":"pone.0328650.ref006","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41586-022-05448-9","article-title":"Common and rare variant associations with clonal haematopoiesis phenotypes","volume":"612","author":"MD Kessler","year":"2022","journal-title":"Nature"},{"issue":"20","key":"pone.0328650.ref007","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1182\/blood.2024024187","article-title":"JAK2-mutant clonal hematopoiesis is associated with venous thromboembolism","volume":"144","author":"RL Zon","year":"2024","journal-title":"Blood"},{"key":"pone.0328650.ref008","doi-asserted-by":"crossref","DOI":"10.1161\/01.CIR.0000078468.11849.66","article-title":"The epidemiology of venous thromboembolism","volume":"107","author":"RH White","year":"2003","journal-title":"Circulation"},{"key":"pone.0328650.ref009","doi-asserted-by":"crossref","first-page":"103964","DOI":"10.1016\/j.ebiom.2022.103964","article-title":"Prevalence and prognostic significance of DNMT3A- and TET2- clonal haematopoiesis-driver mutations in patients presenting with ST-segment elevation myocardial infarction","volume":"78","author":"S Wang","year":"2022","journal-title":"EBioMedicine"},{"key":"pone.0328650.ref010","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1182\/blood.2022017661","article-title":"Associations of clonal hematopoiesis with recurrent vascular events and death in patients with incident ischemic stroke","volume":"141","author":"CM Arends","year":"2023","journal-title":"Blood"},{"issue":"2","key":"pone.0328650.ref011","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1182\/bloodadvances.2024014430","article-title":"CHIP away at the marrow-clot connection: inflammation, clonal hematopoiesis, and thromboembolic disease","volume":"9","author":"A Todorovski","year":"2025","journal-title":"Blood Adv"},{"issue":"1","key":"pone.0328650.ref012","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2046-4053-4-1","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement","volume":"4","author":"D Moher","year":"2015","journal-title":"Syst Rev"},{"key":"pone.0328650.ref013","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/jrsm.1508","article-title":"Including non\u2010English language articles in systematic reviews: a reflection on processes for identifying low\u2010cost sources of translation support","volume":"13","author":"L Rockliffe","year":"2022","journal-title":"Res Synth Methods"},{"issue":"6465","key":"pone.0328650.ref014","doi-asserted-by":"crossref","DOI":"10.1126\/science.aan4673","article-title":"Clonal hematopoiesis in human aging and disease","volume":"366","author":"S Jaiswal","year":"2019","journal-title":"Science"},{"key":"pone.0328650.ref015","article-title":"A practical approach to curate clonal hematopoiesis of indeterminate potential in human genetic datasets","author":"C Vlasschaert","year":"2023","journal-title":"Blood"},{"issue":"3","key":"pone.0328650.ref016","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1001\/jamacardio.2023.5106","article-title":"Clonal hematopoiesis and coronary artery disease-a deep connection","volume":"9","author":"JJ Fuster","year":"2024","journal-title":"JAMA Cardiol"},{"issue":"3","key":"pone.0328650.ref017","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1001\/jamacardio.2023.5095","article-title":"Somatic and germline variants and coronary heart disease in a Chinese population","volume":"9","author":"K Zhao","year":"2024","journal-title":"JAMA Cardiol"},{"issue":"2","key":"pone.0328650.ref018","article-title":"Assessing full benefit of rivaroxaban prophylaxis in high-risk ambulatory patients with cancer: thromboembolic events in the randomized CASSINI trial","volume":"4","author":"AA Khorana","year":"2020","journal-title":"TH Open"},{"key":"pone.0328650.ref019","first-page":"833","article-title":"AHA\/ACC\/ACCP\/ASPC\/NLA\/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association\/American College of Cardiology Joint Committee on Clinical Practice Guidelines","volume":"202382","author":"Writing Committee Members","year":"2023","journal-title":"J Am Coll Cardiol"},{"issue":"20","key":"pone.0328650.ref020","doi-asserted-by":"crossref","DOI":"10.1161\/CIR.0000000000000617","article-title":"Fourth Universal Definition of Myocardial Infarction (2018)","volume":"138","author":"K Thygesen","year":"2018","journal-title":"Circulation"},{"issue":"7","key":"pone.0328650.ref021","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1161\/STR.0b013e318296aeca","article-title":"An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association\/American Stroke Association","volume":"44","author":"RL Sacco","year":"2013","journal-title":"Stroke"},{"issue":"4","key":"pone.0328650.ref022","doi-asserted-by":"crossref","first-page":"280","DOI":"10.7326\/0003-4819-158-4-201302190-00009","article-title":"Assessing bias in studies of prognostic factors","volume":"158","author":"JA Hayden","year":"2013","journal-title":"Ann Intern Med"},{"issue":"3","key":"pone.0328650.ref023","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"R DerSimonian","year":"1986","journal-title":"Control Clin Trials"},{"key":"pone.0328650.ref024","volume-title":"GRADE handbook for grading quality of evidence and strength of recommendations.","author":"HBJ Sch\u00fcnemann","year":"2013"},{"key":"pone.0328650.ref025","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"MJ Page","year":"2021","journal-title":"BMJ"},{"key":"pone.0328650.ref026","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.jacc.2019.06.007","article-title":"Clonal hematopoiesis: crossroads of aging, cardiovascular disease, and cancer: JACC review topic of the week","volume":"74","author":"P Libby","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"pone.0328650.ref027","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1001\/jamacardio.2022.0386","article-title":"TET2-Driven clonal hematopoiesis and response to canakinumab: an exploratory analysis of the CANTOS randomized clinical trial","volume":"7","author":"EC Svensson","year":"2022","journal-title":"JAMA Cardiology"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0328650","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T17:31:02Z","timestamp":1752687062000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0328650"}},"subtitle":[],"editor":[{"given":"Ey\u00fcp Serhat","family":"\u00c7al\u0131k","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,7,16]]},"references-count":27,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0328650","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,16]]}}}