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In malaria\u2010endemic Papua, Indonesia, we prospectively analyzed red blood cell (RBC) concentrations in the spleen and spleen\u2010mimetic retention in 37 subjects splenectomized for trauma or hyperreactive splenomegaly, most of whom were infected with <jats:italic>Plasmodium<\/jats:italic>. Splenomegaly (median 357\u2009g [range: 80\u20131918\u2009g]) was correlated positively with the proportion of red\u2010pulp on histological sections (median 88.1% [range: 74%\u201399.4%]; <jats:italic>r<\/jats:italic>\u2009=\u2009.59, <jats:italic>p<\/jats:italic>\u2009=\u2009.0003) and correlated negatively with the proportion of white\u2010pulp (median 8.3% [range: 0.4%\u201322.9%]; <jats:italic>r<\/jats:italic>\u2009=\u2009\u2212.50, <jats:italic>p<\/jats:italic>\u2009=\u2009.002). The number of RBC per microscopic field (&gt;95% uninfected) was correlated positively with spleen weight in both Pf\u2010infected (<jats:italic>r<\/jats:italic>\u2009=\u2009.73; <jats:italic>p<\/jats:italic>\u2009=\u2009.017) and Pv\u2010infected spleens (<jats:italic>r<\/jats:italic>\u2009=\u2009.94; <jats:italic>p<\/jats:italic>\u2009=\u2009.006). The median estimated proportion of total\u2010body RBCs retained in Pf\u2010infected spleens was 8.2% (range: 1.0%\u201333.6%), significantly higher than in Pv\u2010infected (2.6% [range: 0.6%\u201323.8%]; <jats:italic>p<\/jats:italic>\u2009=\u2009.015) and PCR\u2010negative subjects (2.5% [range: 1.0%\u20133.3%]; <jats:italic>p<\/jats:italic>\u2009=\u2009.006). Retained RBCs accounted for over half of circulating RBC loss seen in Pf infections. The proportion of total\u2010body RBC retained in Pf\u2010 and Pv\u2010infected spleens correlated negatively with hemoglobin concentrations (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212.56, <jats:italic>p<\/jats:italic>\u2009=\u2009.0003), hematocrit (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212.58, <jats:italic>p<\/jats:italic>\u2009=\u2009.0002), and circulating RBC counts (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212.56, <jats:italic>p<\/jats:italic>\u2009=\u2009.0003). Splenic CD71\u2010positive reticulocyte concentrations correlated with spleen weight in Pf (r\u2009=\u20091.0; <jats:italic>p<\/jats:italic>\u2009=\u2009.003). Retention rates of peripheral and splenic RBCs were correlated negatively with circulating RBC counts (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212.69, <jats:italic>p<\/jats:italic>\u2009=\u2009.07 and <jats:italic>r<\/jats:italic>\u2009=\u2009\u2212.83, <jats:italic>p<\/jats:italic>\u2009=\u2009.008, respectively). In conclusion, retention of mostly uninfected RBC in the spleen, leading to marked congestion of the red\u2010pulp, was associated with splenomegaly and is the major mechanism of anemia in subjects infected with <jats:italic>Plasmodium<\/jats:italic>, particularly Pf.<\/jats:p>","DOI":"10.1002\/ajh.27152","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T22:41:06Z","timestamp":1701124866000},"page":"223-235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Retention of uninfected red blood cells causing congestive splenomegaly is the major mechanism of anemia in malaria"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0926-8049","authenticated-orcid":false,"given":"Steven","family":"Kho","sequence":"first","affiliation":[{"name":"Global and Tropical Health Division Menzies School of Health Research and Charles Darwin University  Darwin Northern Territory Australia"},{"name":"Timika Malaria Research Program Papuan Health and Community Development Foundation  Timika Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurjati C.","family":"Siregar","sequence":"additional","affiliation":[{"name":"Eijkman Institute for Molecular Biology  Jakarta Indonesia"},{"name":"Department of Anatomical Pathology Rumah Sakit Cipto Mangunkusumo and Universitas Indonesia  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Labibah","family":"Qotrunnada","sequence":"additional","affiliation":[{"name":"Eijkman Institute for Molecular Biology  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Fricot","sequence":"additional","affiliation":[{"name":"UMR_S1134, BIGR, Inserm, Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9986-0494","authenticated-orcid":false,"given":"Abdoulaye","family":"Sissoko","sequence":"additional","affiliation":[{"name":"UMR_S1134, BIGR, Inserm, Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Putu A. 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