{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T12:40:06Z","timestamp":1740141606185,"version":"3.37.3"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T00:00:00Z","timestamp":1422921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100015079","name":"ARUP Laboratories","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015079","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cytometry Part B Clinical"],"published-print":{"date-parts":[[2015,7,8]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by increased complement\u2010mediated lysis of erythrocytes (RBCs) because of low\/absent glycophosphatidylinositol (GPI) anchors of numerous cell surface proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rare event analysis was applied to 120 million RBCs (12 normal individuals) and 102 million RBCs (102 normal individuals) to establish a reference range and verify a methodology for rare event analysis. Patient PNH testing (<jats:italic>n<\/jats:italic>\u2009=\u200910,984) was performed over 47 months using the 2010 consensus guidelines with CD59\u2010PE and glycophorin A\u2010FITC for RBCs and FLAER\u2010Alexa 488, CD33\u2010PerCP\u2010Cy5.5, CD15\u2010APC, CD14\u2010APC\u2010Cy7, and CD24\u2010PE for WBCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The distribution of CD59<jats:bold>\u2212<\/jats:bold>RBCs in the normal population was asymmetric with a mean of 5.9, median between 3 and 4, and mode of 2 per million RBCs. The normal range of CD59<jats:bold>\u2212<\/jats:bold>RBCs was 0\u201017\/million RBCs. A natural cutoff of 2.5% of the peak expression of CD59 delineates CD59+ from CD59<jats:bold>\u2212<\/jats:bold>populations. The incidence of GPI\u2010 samples received by the laboratory was 6\u20137% without correlation to age (<jats:italic>P<\/jats:italic>\u2009=\u20090.35) or sex (<jats:italic>P<\/jats:italic>\u2009=\u20090.45). The percentage of GPI\u2010 neutrophils and monocytes were strongly correlated (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.96) and usually greater than the percentage of GPI\u2010 RBCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PNH RBC testing is a good example of rare event analysis applied to clinical cytometry\u2014only 2.5 min are required to collect 1 million RBCs. With an established normal range of CD59<jats:bold>\u2212<\/jats:bold>RBCs, the correlation between total cell count and sensitivity for detecting an abnormal population can be calculated using Poisson statistics. \u00a9 2015 International Clinical Cytometry Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/cyto.b.21225","type":"journal-article","created":{"date-parts":[[2015,1,20]],"date-time":"2015-01-20T22:23:11Z","timestamp":1421792591000},"page":"261-269","source":"Crossref","is-referenced-by-count":6,"title":["Rare event counting of CD59\u2212 red cells in human blood: A 47\u2010month experience using PNH consensus guidelines for WBC and RBC testing in a reference lab"],"prefix":"10.1002","volume":"88","author":[{"given":"Michael","family":"Liew","sequence":"first","affiliation":[{"name":"Institute for Clinical and Experimental Pathology, ARUP Laboratories Salt Lake City Utah 84108"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjorie","family":"Farley","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Pathology, ARUP Laboratories Salt Lake City Utah 84108"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Andreasen","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Pathology, ARUP Laboratories Salt Lake City Utah 84108"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles J.","family":"Parker","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Internal Medicine University of Utah School of Medicine Salt Lake City Utah 84132"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl T.","family":"Wittwer","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Pathology, ARUP Laboratories Salt Lake City Utah 84108"},{"name":"Department of Pathology University of Utah School of Medicine Salt Lake City Utah 84132"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,2,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2010.04.002"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/cyto.b.20525","article-title":"Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry","volume":"78","author":"Borowitz MJ","year":"2010","journal-title":"Cytom B Clin Cytom"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1182\/blood.V8.9.769.769","article-title":"Paroxysmal nocturnal hemoglobinuria: Relation of the clinical manifestations to underlying pathogenic mechanisms","volume":"8","author":"Crosby 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