{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T11:01:19Z","timestamp":1762254079155,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T00:00:00Z","timestamp":1645920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Circulating endothelial cells (CECs) are viable, apoptotic or necrotic cells, identified by CD 146 surface antigen expression, considered a biomarker of thrombotic risk, given their active role in inflammatory, procoagulant and immune processes of the vascular compartment. Growing evidence establishes that CECs are also involved in the pathogenesis of several hematological and solid malignancies. The primary aim of this study was to verify if CEC levels could predict both the course and treatment responses of splanchnic vein thrombosis (SVT), either in patients affected by myeloproliferative neoplasms (MPNs) or liver disease. Thus, a retrospective multicenter study was performed; fifteen patients receiving anticoagulant oral treatment with vitamin k antagonists (VKA) for SVT were evaluated. Nine patients were affected by MPN, and all of them received cytoreduction in addition to anticoagulant therapy; four of these patients had primary myelofibrosis (PMF) and were treated with ruxolitinib (RUX), and one patient with primary myelofibrosis, two patients with essential thrombocythemia (ET), and two patients with polycythemia vera (PV) were treated with hydroxyurea (HU). Six patients affected by liver diseases (three with liver cirrhosis and three with hepatocellular carcinoma) were included as the control group. CECs were assayed by flow cytometry on peripheral blood at specific time points, for up to six months after enrollment. The CEC levels were related to C-reactive protein (CRP) levels, splenic volume reduction, and thrombus recanalization, mainly in MPN patients. In patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC), for which the mechanism of SVT development is quite different, the relationship between CEC and SV reduction was absent. In conclusion, the CEC levels showed a significant correlation with the extent of venous thrombosis and endothelial cell damage in myeloproliferative neoplasm patients with splanchnic vein thrombosis. Although preliminary, these results show how monitoring CEC levels during cytoreductive and anticoagulant treatments may be useful to improve SVT outcome in MPN patients.<\/jats:p>","DOI":"10.3390\/jpm12030364","type":"journal-article","created":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T20:47:17Z","timestamp":1645994837000},"page":"364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Circulating Endothelial Cell Levels Correlate with Treatment Outcomes of Splanchnic Vein Thrombosis in Patients with Chronic Myeloproliferative Neoplasms"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6932-5028","authenticated-orcid":false,"given":"Giulio","family":"Giordano","sequence":"first","affiliation":[{"name":"Internal Medicine Division, Hematology Service, Regional Hospital \u201cA. Cardarelli\u201d, 86100 Campobasso, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariasanta","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties and Haematology Unit, University Hospital \u201cP. Giaccone\u201d, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Cellurale","sequence":"additional","affiliation":[{"name":"Internal Medicine Division, Hematology Service, Regional Hospital \u201cA. Cardarelli\u201d, 86100 Campobasso, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4418-5855","authenticated-orcid":false,"given":"Paola","family":"Di Carlo","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother, and Child Care, Internal Medicine and Medical Specialties and Infectious Disease Unit, University Hospital \u201cP. Giaccone\u201d, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerardo","family":"Musuraca","sequence":"additional","affiliation":[{"name":"Hematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Micucci","sequence":"additional","affiliation":[{"name":"Hematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0624-5311","authenticated-orcid":false,"given":"Alessandro","family":"Lucchesi","sequence":"additional","affiliation":[{"name":"Hematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1111\/j.1538-7836.2008.02918.x","article-title":"Circulating endothelial cells: From bench to clinical practice","volume":"6","author":"Shantsila","year":"2008","journal-title":"J. Thromb. Haemost."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1093\/ndt\/17.10.1728","article-title":"Circulating endothelial cells: Life, death, detachment and repair of the endothelial cell layer","volume":"17","author":"Woywodt","year":"2002","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.1182\/blood-2006-06-026187","article-title":"Engulfment of apoptotic cells by microvascular endothelial cells induces proinflammatory responses","volume":"109","author":"Kirsch","year":"2007","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3658","DOI":"10.1182\/blood.V97.11.3658","article-title":"Resting and activated endothelial cells are increased in the peripheral blood of cancer patients","volume":"97","author":"Mancuso","year":"2001","journal-title":"Blood"},{"key":"ref_5","first-page":"4341","article-title":"Kinetics and viability of circulating endothelial cells as surrogate angiogenesis marker in an animal model of human lymphoma","volume":"61","author":"Monestiroli","year":"2001","journal-title":"Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/nm0603-702","article-title":"Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration","volume":"9","author":"Rafii","year":"2003","journal-title":"Nat. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1038\/nm1101-1194","article-title":"Impaired recruitment of bone-marrow\u2013derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth","volume":"7","author":"Lyden","year":"2001","journal-title":"Nat. Med."},{"key":"ref_8","first-page":"7654","article-title":"Mobilized Human CD34+ Hematopoietic Stem Cells Enhance Tumor Growth in a Nonobese Diabetic\/Severe Combined Immunodeficient Mouse Model of Human Non-Hodgkin\u2019s Lymphoma","volume":"61","author":"Guikema","year":"2001","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/annonc\/mdh017","article-title":"Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients","volume":"15","author":"Beerepoot","year":"2004","journal-title":"Ann. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Torres, C., Fonseca, A.M., Leander, M., Matos, R., Morais, S., Campos, M., and Lima, M. (2013). Circulating endothelial cells in patients with venous thromboembolism and myeloproliferative neoplasms. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081574"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1111\/bjh.12461","article-title":"Splanchnic vein thrombosis in myeloproliferative neoplasms","volume":"162","author":"Sekhar","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1182\/blood-2009-08-238956","article-title":"Thrombosis in primary myelofibrosis: Incidence and risk factors","volume":"115","author":"Barbui","year":"2010","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1007\/s00277-014-2224-8","article-title":"Prophylaxis and management of venous thromboembolism in patients with myeloproliferative neoplasms: Consensus statement of the Haemostasis Working Party of the German Society of Hematology and Oncology (DGHO), the Austrian Society of Hematology and Oncology (\u00d6GHO) and Society of Thrombosis and Haemostasis Research (GTH e.V.)","volume":"93","author":"Kreher","year":"2014","journal-title":"Ann. Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.7150\/ijms.6887","article-title":"Circulating Progenitor and Mature Endothelial Cells in Deep Vein Thrombosis","volume":"10","author":"Alessio","year":"2013","journal-title":"Int. J. Med. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1001\/jamainternmed.2015.3184","article-title":"Long-term Clinical Outcomes of Splanchnic Vein Thrombosis","volume":"175","author":"Ageno","year":"2015","journal-title":"JAMA Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4922","DOI":"10.1182\/blood-2007-11-125328","article-title":"The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: A report on 241 cases","volume":"111","author":"Kiladjian","year":"2008","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1182\/blood-2013-03-460154","article-title":"Myeloproliferative neoplasms and thrombosis","volume":"122","author":"Barbui","year":"2013","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s12185-010-0530-z","article-title":"Molecular aspects of myeloproliferative neoplasms","volume":"91","author":"Delhommeau","year":"2010","journal-title":"Int. J. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1056\/NEJMoa1409002","article-title":"Ruxolitinib versus Standard Therapy for the Treatment of Polycythemia Vera","volume":"372","author":"Vannucchi","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1056\/NEJMoa1110557","article-title":"A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis","volume":"366","author":"Verstovsek","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1182\/blood.V124.21.1847.1847","article-title":"Long-Term Results from a Phase II Open-Label Study of Ruxolitinib in Patients with Essential Thrombocythemia Refractory to or Intolerant of Hydroxyurea","volume":"124","author":"Verstovsek","year":"2014","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1177\/2040620716680333","article-title":"Splanchnic vein thrombosis in myeloproliferative neoplasms: Pathophysiology and molecular mechanisms of disease","volume":"8","author":"How","year":"2017","journal-title":"Ther. Adv. Hematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1111\/j.1538-7836.2006.02194.x","article-title":"Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: A new effect for an old drug?","volume":"4","author":"Maugeri","year":"2006","journal-title":"J. Thromb. Haemost."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1160\/TH09-09-0663","article-title":"Nitric oxide derivatives and soluble plasma selectins in patients with myeloproliferative neoplasms","volume":"104","author":"Cella","year":"2010","journal-title":"Thromb. Haemost."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"730","DOI":"10.3324\/haematol.2014.119727","article-title":"Key endothelial cell angiogenic mechanisms are stimulated by the circulating milieu in sickle cell disease and attenuated by hydroxyurea","volume":"100","author":"Lopes","year":"2015","journal-title":"Haematologica"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"534","DOI":"10.3324\/haematol.2010.026740","article-title":"Differential modulation of adhesion molecule expression by hydroxycarbamide in human endothelial cells from the micro- and macrocirculation: Potential implications in sickle cell disease vasoocclusive events","volume":"96","author":"Laurance","year":"2011","journal-title":"Haematologica"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lucchesi, A., Napolitano, R., Bochicchio, M.T., Giordano, G., and Napolitano, M. (2021). Platelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The \u2018Circulating Wound\u2019 Model. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111343"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/blood-2020-140116","article-title":"Ruxolitinib Reduces Endothelial Pro-Adhesive Interactions: Implications for JAK2V617+ MPN Thrombosis","volume":"136","author":"DaSilva","year":"2020","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1182\/blood-2008-07-170449","article-title":"New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment","volume":"113","author":"Cervantes","year":"2009","journal-title":"Blood"},{"key":"ref_30","first-page":"287","article-title":"Serum C-reactive protein and circulating endothelial cells in patients with acute myocardial infarction","volume":"32","author":"Wang","year":"2005","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s11899-013-0176-z","article-title":"Are MPNs Vascular Diseases?","volume":"8","author":"Finazzi","year":"2013","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1210\/er.2007-0001","article-title":"The Complex Role of Estrogens in Inflammation","volume":"28","author":"Straub","year":"2007","journal-title":"Endocr. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/bjh.13080","article-title":"A lower intensity of treatment may underlie the increased risk of thrombosis in young patients with masked polycythaemia vera","volume":"167","author":"Lussana","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lubberich, R.K., Walenda, T., Goecke, T.W., Strathmann, K., Isfort, S., Br\u00fcmmendorf, T.H., Koschmieder, S., and Wagner, W. (2018). Serum of myeloproliferative neoplasms stimulates hematopoietic stem and progenitor cells. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197233"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3324\/haematol.2016.149559","article-title":"Associations between gender, disease features and symptom burden in patients with myeloproliferative neoplasms: An analysis by the MPN QOL International Working Group","volume":"102","author":"Geyer","year":"2017","journal-title":"Haematologica"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1182\/blood-2009-04-214957","article-title":"Preclinical characterization of the selective JAK1\/2 inhibitor INCB018424: Therapeutic implications for the treatment of myeloproliferative neoplasms","volume":"115","author":"Vaddi","year":"2010","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1182\/blood-2012-01-404889","article-title":"Spleen endothelial cells from patients with myelofibrosis harbor the JAK2V617F mutation","volume":"121","author":"Rosti","year":"2013","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1182\/blood-2010-07-297598","article-title":"Endothelial progenitor cells are clonal and exhibit the JAK2V617F mutation in a subset of thrombotic patients with Ph-negative myeloproliferative neoplasms","volume":"117","author":"Teofili","year":"2011","journal-title":"Blood"},{"key":"ref_39","first-page":"453","article-title":"D-dimer as a potential clinical marker for predicting metastasis and progression in cancer","volume":"9","author":"Dai","year":"2018","journal-title":"Biomed. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5246","DOI":"10.1182\/blood-2008-11-191544","article-title":"The presence of JAK2V617F mutation in the liver endothelial cells of patients with Budd-Chiari syndrome","volume":"113","author":"Sozer","year":"2009","journal-title":"Blood"},{"key":"ref_41","first-page":"96","article-title":"A prominent role of D-dimer in inflammation and atherosclerosis","volume":"1","author":"Myasoedova","year":"2017","journal-title":"Vessel Plus"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.3389\/fonc.2019.01186","article-title":"Mechanisms Underlying the Anti-inflammatory and Immunosuppressive Activity of Ruxolitinib","volume":"9","author":"Elli","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1097\/MBC.0000000000000446","article-title":"The impact of ruxolitinib on thrombosis in patients with polycythemia vera and myelofibrosis","volume":"27","author":"Samuelson","year":"2016","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/ajh.24614","article-title":"Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms","volume":"92","author":"Pieri","year":"2017","journal-title":"Am. J. Hematol."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/3\/364\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:28:38Z","timestamp":1760135318000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/3\/364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,27]]},"references-count":44,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["jpm12030364"],"URL":"https:\/\/doi.org\/10.3390\/jpm12030364","relation":{},"ISSN":["2075-4426"],"issn-type":[{"type":"electronic","value":"2075-4426"}],"subject":[],"published":{"date-parts":[[2022,2,27]]}}}