{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:56:30Z","timestamp":1791309390169,"version":"4.3.1"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2016,1,19]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Beh\u00e7et disease (BD) is a systemic vasculitis with a broad range of organ involvement, characterized by a multisystemic, immune-inflammatory disorder involving vessels of all sizes and often complicated by thrombosis. Systemic redox imbalance and circulating neutrophil hyperactivation have been observed in BD patients and are thought to be responsible for impaired coagulation. We here focused on the pathogenetic mechanisms potentially linking immune cell activation and thrombosis, and specifically examined whether neutrophil activation can affect fibrinogen modifications and consequently elicit thrombosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Blood samples were collected from 98 consecutive BD patients attending our dedicated Center and from 70 age- and sex-matched healthy controls; in all patients fibrinogen function and structure, fibrin susceptibility to plasmin-lysis, plasma redox status, leukocyte oxidative stress markers, and possible reactive oxygen species sources were examined. Thrombin-catalyzed fibrin formation and fibrin susceptibility to plasmin-induced lysis were significantly impaired in BD patients (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). These findings were associated with increased plasma oxidative stress markers (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and with a marked carbonylation of fibrinogen (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001), whose secondary structure appeared deeply modified. Neutrophils displayed an enhanced NADPH oxidase activity and increased reactive oxygen species production (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001), which significantly correlated with fibrinogen carbonylation level (\n              <jats:italic>r<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\n              =0.33,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001), residual \u03b2-band intensity (\n              <jats:italic>r<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\n              =0.07,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01), and fibrinogen clotting ability (\n              <jats:italic>r<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\n              =0.073,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01)\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>In BD patients, altered fibrinogen structure and impaired fibrinogen function are associated with neutrophil activation and enhanced reactive oxygen species production whose primary source is represented by neutrophil NADPH oxidase.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.115.017738","type":"journal-article","created":{"date-parts":[[2016,1,11]],"date-time":"2016-01-11T23:02:42Z","timestamp":1452553362000},"page":"302-311","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":167,"title":["Neutrophil Activation Promotes Fibrinogen Oxidation and Thrombus Formation in Beh\u00e7et Disease"],"prefix":"10.1161","volume":"133","author":[{"given":"Matteo","family":"Becatti","sequence":"first","affiliation":[{"name":"From Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d (M.B., G.B., N.T., C.F.) and Department of Experimental and Clinical Medicine (G.E., E.S., L.C., D.S., R.A., D.P.), University of Florence, Italy; Nephrology Unit, University Hospital of Parma, Italy (A.V.); Interdisciplinary Internal Medicine, Center for Autoimmune Systemic Diseases, Beh\u00e7et Center and Lupus Clinic, AOU Careggi, Florence, Italy (L.E., D.P.); and Department of Clinical and Experimental Medicine, University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Emmi","sequence":"additional","affiliation":[{"name":"From Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d (M.B., G.B., N.T., C.F.) and Department of Experimental and Clinical Medicine (G.E., E.S., L.C., D.S., R.A., D.P.), University of Florence, Italy; Nephrology Unit, University Hospital of Parma, Italy (A.V.); Interdisciplinary Internal Medicine, Center for Autoimmune Systemic Diseases, Beh\u00e7et Center and Lupus Clinic, AOU Careggi, Florence, Italy (L.E., D.P.); and Department of Clinical and Experimental Medicine, University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Silvestri","sequence":"additional","affiliation":[{"name":"From Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d (M.B., G.B., N.T., C.F.) and Department of Experimental and Clinical Medicine (G.E., E.S., L.C., D.S., R.A., D.P.), University of Florence, Italy; Nephrology Unit, University Hospital of Parma, Italy (A.V.); Interdisciplinary Internal Medicine, Center for Autoimmune Systemic Diseases, Beh\u00e7et Center and Lupus Clinic, AOU Careggi, Florence, Italy (L.E., D.P.); and Department of Clinical and Experimental Medicine, University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Bruschi","sequence":"additional","affiliation":[{"name":"From Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d (M.B., G.B., N.T., C.F.) and Department of Experimental and Clinical Medicine (G.E., E.S., L.C., D.S., R.A., D.P.), University of Florence, Italy; Nephrology Unit, University Hospital of Parma, Italy (A.V.); Interdisciplinary Internal Medicine, Center for Autoimmune Systemic Diseases, Beh\u00e7et Center and Lupus Clinic, AOU Careggi, Florence, Italy (L.E., D.P.); and Department of Clinical and Experimental Medicine, University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Ciucciarelli","sequence":"additional","affiliation":[{"name":"From Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d (M.B., G.B., N.T., C.F.) and Department of Experimental and Clinical Medicine (G.E., E.S., L.C., D.S., R.A., D.P.), University of Florence, Italy; Nephrology Unit, University Hospital of Parma, Italy (A.V.); Interdisciplinary Internal Medicine, Center for Autoimmune Systemic Diseases, Beh\u00e7et Center and Lupus Clinic, AOU Careggi, Florence, Italy (L.E., D.P.); and Department of Clinical and Experimental Medicine, University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danilo","family":"Squatrito","sequence":"additional","affiliation":[{"name":"From Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d (M.B., G.B., N.T., C.F.) and Department of Experimental and Clinical Medicine (G.E., E.S., L.C., D.S., R.A., D.P.), University of Florence, Italy; Nephrology Unit, University Hospital of Parma, Italy (A.V.); Interdisciplinary Internal Medicine, Center for Autoimmune Systemic Diseases, Beh\u00e7et Center and Lupus Clinic, AOU Careggi, Florence, Italy (L.E., D.P.); and Department of Clinical and Experimental Medicine, University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto","family":"Vaglio","sequence":"additional","affiliation":[{"name":"From Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d (M.B., G.B., N.T., C.F.) and Department of Experimental and Clinical Medicine (G.E., E.S., L.C., D.S., R.A., D.P.), University of Florence, Italy; Nephrology Unit, University Hospital of Parma, Italy (A.V.); Interdisciplinary Internal Medicine, Center for Autoimmune Systemic Diseases, Beh\u00e7et Center and Lupus Clinic, AOU Careggi, Florence, Italy (L.E., D.P.); and Department of Clinical and Experimental Medicine, University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niccol\u00f2","family":"Taddei","sequence":"additional","affiliation":[{"name":"From Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d (M.B., G.B., N.T., C.F.) and Department of Experimental and Clinical Medicine (G.E., E.S., L.C., D.S., R.A., D.P.), University of Florence, Italy; Nephrology Unit, University Hospital of Parma, Italy (A.V.); Interdisciplinary Internal Medicine, Center for Autoimmune Systemic Diseases, Beh\u00e7et Center and Lupus Clinic, AOU Careggi, Florence, Italy (L.E., D.P.); and Department of Clinical and Experimental Medicine, University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Abbate","sequence":"additional","affiliation":[{"name":"From Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d (M.B., G.B., N.T., C.F.) and Department of Experimental and Clinical Medicine (G.E., E.S., L.C., D.S., R.A., D.P.), University of Florence, Italy; Nephrology Unit, University Hospital of Parma, Italy (A.V.); Interdisciplinary Internal Medicine, Center for Autoimmune Systemic Diseases, Beh\u00e7et Center and Lupus Clinic, AOU Careggi, Florence, Italy (L.E., D.P.); and Department of Clinical and Experimental Medicine, University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Emmi","sequence":"additional","affiliation":[{"name":"From Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d (M.B., G.B., N.T., C.F.) and Department of Experimental and Clinical Medicine (G.E., E.S., L.C., D.S., R.A., D.P.), University of Florence, Italy; Nephrology Unit, University Hospital of Parma, Italy (A.V.); Interdisciplinary Internal Medicine, Center for Autoimmune Systemic Diseases, Beh\u00e7et Center and Lupus Clinic, AOU Careggi, Florence, Italy (L.E., D.P.); and Department of Clinical and Experimental Medicine, University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Goldoni","sequence":"additional","affiliation":[{"name":"From Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d (M.B., G.B., N.T., C.F.) and Department of Experimental and Clinical Medicine (G.E., E.S., L.C., D.S., R.A., D.P.), University of Florence, Italy; Nephrology Unit, University Hospital of Parma, Italy (A.V.); Interdisciplinary Internal Medicine, Center for Autoimmune Systemic Diseases, Beh\u00e7et Center and Lupus Clinic, AOU Careggi, Florence, Italy (L.E., D.P.); and Department of Clinical and Experimental Medicine, University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Fiorillo","sequence":"additional","affiliation":[{"name":"From Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d (M.B., G.B., N.T., C.F.) and Department of Experimental and Clinical Medicine (G.E., E.S., L.C., D.S., R.A., D.P.), University of Florence, Italy; Nephrology Unit, University Hospital of Parma, Italy (A.V.); Interdisciplinary Internal Medicine, Center for Autoimmune Systemic Diseases, Beh\u00e7et Center and Lupus Clinic, AOU Careggi, Florence, Italy (L.E., D.P.); and Department of Clinical and Experimental Medicine, University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Prisco","sequence":"additional","affiliation":[{"name":"From Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d (M.B., G.B., N.T., C.F.) and Department of Experimental and Clinical Medicine (G.E., E.S., L.C., D.S., R.A., D.P.), University of Florence, Italy; Nephrology Unit, University Hospital of Parma, Italy (A.V.); Interdisciplinary Internal Medicine, Center for Autoimmune Systemic Diseases, Beh\u00e7et Center and Lupus Clinic, AOU Careggi, Florence, Italy (L.E., D.P.); and Department of Clinical and Experimental Medicine, University..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.65.2.287"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/138161212799504731"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2012.11.028"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-012-0295-3"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-010-0239-3"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-10-463646"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2009.03921.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3345"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-381400"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112322"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.37715"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199910213411707"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e3283410088"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.7754\/Clin.Lab.2012.120722"},{"key":"e_1_3_3_16_2","first-page":"13","article-title":"Thrombosis in vasculitis: from pathogenesis to treatment.","volume":"16","author":"Emmi G","year":"2015","unstructured":"Emmi G, Silvestri E, Squatrito D, Amedei A, Niccolai E, D\u2019Elios MM, Della Bella C, Grassi A, Becatti M, Fiorillo C, Emmi L, Vaglio A, Prisco D. 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