{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T15:59:38Z","timestamp":1787932778514,"version":"build-2784847793"},"reference-count":43,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rare, congenital nonimmune hemolytic disorders of the erythrocyte, although uncommon, are important causes of anemia in the child and adult. These are a heterogeneous group of diseases that disrupt normal erythrocyte structure and function in varying ways. Predominant are abnormalities of hemoglobin stability, defects of erythrocyte metabolism, and disorders of erythrocyte hydration. Unstable hemoglobinopathies may lead to chronic or episodic hemolysis. Perturbation of critical enzymes of the Embden\u2013Meyerhof pathway lead to altered erythrocyte metabolism and chronic hemolysis. Disorders of erythrocyte hydration are an under-recognized cause of hemolytic anemia. Beyond pathophysiologic mechanisms of disease, clinical, laboratory, and genetic heterogeneity characterize this group of disorders. Often, they are underdiagnosed or misdiagnosed. This review discusses pathophysiology, inheritance, clinical findings, laboratory manifestations, and management considerations in several rare nonimmune hemolytic diseases including the unstable hemoglobins, disorders of erythrocyte metabolism, and abnormalities of erythrocyte hydration.<\/jats:p>","DOI":"10.1182\/asheducation-2015.1.392","type":"journal-article","created":{"date-parts":[[2016,9,15]],"date-time":"2016-09-15T15:23:25Z","timestamp":1473953005000},"page":"392-399","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":40,"title":["Diagnosis and management of rare congenital nonimmune hemolytic disease"],"prefix":"10.1182","volume":"2015","author":[{"given":"Patrick G.","family":"Gallagher","sequence":"first","affiliation":[{"name":"Departments of Pediatrics, Pathology, and Genetics, Yale University School of Medicine, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"7","key":"2019111702582800300_B1","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1002\/pbc.22702","article-title":"The diagnostic dilemma of congenital unstable hemoglobinopathies","volume":"55","author":"Yates","year":"2010","journal-title":"Pediatr Blood Cancer"},{"issue":"2","key":"2019111702582800300_B2","first-page":"128","article-title":"Oxidative hemoglobin denaturation and RBC destruction: the effect of heme on red cell membranes","volume":"26","author":"Chiu","year":"1989","journal-title":"Semin Hematol"},{"issue":"10","key":"2019111702582800300_B3","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1182\/blood.V76.10.2125.2125","article-title":"Effect of hemoglobin oxidation products on the stability of red cell membrane skeletons and the associations of skeletal proteins: correlation with a release of hemin","volume":"76","author":"Jarolim","year":"1990","journal-title":"Blood"},{"key":"2019111702582800300_B4","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1172\/JCI106421","article-title":"The role of hemoglobin heme loss in Heinz body formation: studies with a partially heme-deficient hemoglobin and with genetically unstable hemoglobins","volume":"49","author":"Jacob","year":"1970","journal-title":"J Clin Invest"},{"issue":"4","key":"2019111702582800300_B5","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1080\/03630260701590301","article-title":"Aplastic crisis revealing the diagnosis of Hb Evans [alpha62(E11)Val\u2192Met, GTG\u2192ATG (alpha2)] in a Hispanic kindred: case report and review","volume":"31","author":"Steiner","year":"2007","journal-title":"Hemoglobin"},{"issue":"3","key":"2019111702582800300_B6","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1097\/MPH.0b013e318032568c","article-title":"Pulmonary hypertension in a case of Hb-Mainz hemolytic anemia","volume":"29","author":"Lode","year":"2007","journal-title":"J Pediatr Hematol Oncol"},{"issue":"3","key":"2019111702582800300_B7","first-page":"340","article-title":"Novel human pathological mutations: gene symbol: PKLR. 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