{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:38:58Z","timestamp":1792643938633,"version":"4.5.0"},"reference-count":59,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,3,8]],"date-time":"2010-03-08T00:00:00Z","timestamp":1268006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Pulmonary hypertension (PH) is a common complication of haemolytic anaemia. Intravascular haemolysis leads to nitric oxide (NO) depletion, endothelial and smooth muscle dysregulation, and vasculopathy, characterized by progressive hypertension. PH has been reported in patients with paroxysmal nocturnal haemoglobinuria (PNH), a life\u2010threatening haemolytic disease. We explored the relationship between haemolysis, systemic NO, arginine catabolism and measures of PH in 73 PNH patients enrolled in the placebo\u2010controlled TRIUMPH (Transfusion Reduction Efficacy and Safety Clinical Investigation Using Eculizumab in Paroxysmal Nocturnal Haemoglobinuria) study. At baseline, intravascular haemolysis was associated with elevated NO consumption (\n                    <jats:italic>P\u2003<\/jats:italic>\n                    &lt;\u20030\u00b70001) and arginase\u20101 release (\n                    <jats:italic>P\u2003<\/jats:italic>\n                    &lt;\u20030\u00b70001). Almost half of the patients in the trial had elevated levels (\u2265160\u2003pg\/ml) of\n                    <jats:italic>N<\/jats:italic>\n                    \u2010terminal pro\u2010brain natriuretic peptide (NT\u2010proBNP), a marker of pulmonary vascular resistance and right ventricular dysfunction previously shown to indicate PH. Eculizumab treatment significantly reduced haemolysis (\n                    <jats:italic>P\u2003<\/jats:italic>\n                    &lt;\u20030\u00b7001), NO depletion (\n                    <jats:italic>P<\/jats:italic>\n                    \u2003&lt;\u20030\u00b7001), vasomotor tone (\n                    <jats:italic>P<\/jats:italic>\n                    \u2003&lt;\u20030\u00b705), dyspnoea (\n                    <jats:italic>P\u2003<\/jats:italic>\n                    =\u20030\u00b7006) and resulted in a 50% reduction in the proportion of patients with elevated NT\u2010proBNP (\n                    <jats:italic>P\u2003<\/jats:italic>\n                    &lt;\u20030\u00b7001) within 2\u2003weeks of treatment. Importantly, the significant improvements in dyspnoea and NT\u2010proBNP levels occurred without significant changes in anaemia. These data demonstrated that intravascular haemolysis in PNH produces a state of NO catabolism leading to signs of PH, including elevated NT pro\u2010BNP and dyspnoea that are significantly improved by treatment with eculizumab.\n                  <\/jats:p>","DOI":"10.1111\/j.1365-2141.2010.08096.x","type":"journal-article","created":{"date-parts":[[2010,3,8]],"date-time":"2010-03-08T03:19:09Z","timestamp":1268018349000},"page":"414-425","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Effect of eculizumab on haemolysis\u2010associated nitric oxide depletion, dyspnoea, and measures of pulmonary hypertension in patients with paroxysmal nocturnal haemoglobinuria"],"prefix":"10.1111","volume":"149","author":[{"given":"Anita","family":"Hill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell P.","family":"Rother","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunde","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney M.","family":"Morris, Jr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Quinn\u2010Senger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Richards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Bessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hillmen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Gladwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,4,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013207318697"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.11.3411"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21057"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2006.02.061"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(70)90063-X"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.2.169"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000107251.49515.c2"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V57.1.83.83"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(82)90763-X"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.157.4.9707165"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.88.5.1520"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.5.2007172"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000036268.47509.02"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830160110"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.129.5.1313"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ehj.2003.07.005"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035477"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2005.04.019"},{"key":"e_1_2_8_20_1","first-page":"L97","article-title":"Effects of inhibitors of EDRF and EDHF on vasoreactivity of perfused rat lungs","volume":"260","author":"Hasunuma K.","year":"1991","journal-title":"American Journal of Physiology"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-199812000-00004"},{"key":"e_1_2_8_22_1","first-page":"305a","article-title":"Nitric Oxide Consumption and Pulmonary Hypertension in Patients with Paroxysmal Nocturnal Hemoglobinuria","volume":"106","author":"Hill A.","year":"2005","journal-title":"(Abstract). 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