{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:06:42Z","timestamp":1790384802425,"version":"4.1.0"},"reference-count":55,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,12,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Heterogeneous red blood cell (RBC) membrane disorders and hydration defects often present with the common clinical findings of hemolytic anemia, but they may require substantially different management, based on their pathophysiology. An accurate and timely diagnosis is essential to avoid inappropriate interventions and prevent complications. Advances in genetic testing availability within the last decade, combined with extensive foundational knowledge on RBC membrane structure and function, now facilitate the correct diagnosis in patients with a variety of hereditary hemolytic anemias (HHAs). Studies in patient cohorts with well-defined genetic diagnoses have revealed complications such as iron overload in hereditary xerocytosis, which is amenable to monitoring, prevention, and treatment, and demonstrated that splenectomy is not always an effective or safe treatment for any patient with HHA. However, a multitude of variants of unknown clinical significance have been discovered by genetic evaluation, requiring interpretation by thorough phenotypic assessment in clinical and\/or research laboratories. Here we discuss genotype-phenotype correlations and corresponding clinical management in patients with RBC membranopathies and propose an algorithm for the laboratory workup of patients presenting with symptoms and signs of hemolytic anemia, with a clinical case that exemplifies such a workup.<\/jats:p>","DOI":"10.1182\/hematology.2021000265","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T07:12:29Z","timestamp":1639120349000},"page":"331-340","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":41,"title":["Diagnosis and clinical management of red cell membrane disorders"],"prefix":"10.1182","volume":"2021","author":[{"given":"Theodosia A.","family":"Kalfa","sequence":"first","affiliation":[{"name":"Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"issue":"10","key":"2021121012071584700_hem2021000265C1","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.1172\/JCI119041","article-title":"Combination of two mutant alpha spectrin alleles underlies a severe spherocytic hemolytic anemia","volume":"98","author":"Wichterle","year":"1996","journal-title":"J Clin Invest"},{"issue":"7","key":"2021121012071584700_hem2021000265C2","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1172\/JCI127195","article-title":"Aberrant splicing contributes to severe \u03b1-spectrin-linked congenital hemolytic anemia","volume":"129","author":"Gallagher","year":"2019","journal-title":"J Clin Invest"},{"key":"2021121012071584700_hem2021000265C3","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.3389\/fphys.2019.01331","article-title":"Corrigendum: the spectrum of SPTA1-associated hereditary spherocytosis","volume":"10","author":"Chonat","year":"2019","journal-title":"Front Physiol"},{"issue":"1","key":"2021121012071584700_hem2021000265C4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bcmd.2015.09.001","article-title":"Diagnostic tool for red blood cell membrane disorders: assessment of a new generation ektacytometer","volume":"56","author":"Da Costa","year":"2016","journal-title":"Blood Cells Mol Dis"},{"issue":"11","key":"2021121012071584700_hem2021000265C5","doi-asserted-by":"crossref","first-page":"e28337","DOI":"10.1002\/pbc.28337","article-title":"How I approach hereditary hemolytic anemia and splenectomy","volume":"67","author":"Rothman","year":"2020","journal-title":"Pediatr Blood Cancer"},{"issue":"2","key":"2021121012071584700_hem2021000265C6","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1053\/j.seminhematol.2004.01.002","article-title":"Hereditary spherocytosis\u2014defects in proteins that connect the membrane skeleton to the lipid bilayer","volume":"41","author":"Eber","year":"2004","journal-title":"Semin Hematol"},{"issue":"1","key":"2021121012071584700_hem2021000265C7","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1182\/asheducation-2018.1.377","article-title":"Inherited hemolytic anemia: a possessive beginner's guide","volume":"2018","author":"Mohandas","year":"2018","journal-title":"Hematology Am Soc Hematol Educ Program"},{"issue":"11","key":"2021121012071584700_hem2021000265C8","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1182\/blood.2019000946","article-title":"Red cell membrane disorders: structure meets function","volume":"136","author":"Risinger","year":"2020","journal-title":"Blood"},{"key":"2021121012071584700_hem2021000265C9","first-page":"515","article-title":"Disorders of the red cell membrane","volume-title":"Nathan and Oski's Hematology and Oncology of Infancy and Childhood","author":"Lux","year":"2015"},{"key":"2021121012071584700_hem2021000265C10","unstructured":"Kalfa\n              TA\n            , ConnorJA, BegtrupAH. EPB42-related hereditary spherocytosis. In: AdamMP, ArdingerHH, PagonRA, et al, eds. GeneReviews((R)). 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