Hemolytic Anemias

Chapter 5 - Hemolytic Anemias

Immune- and Non-immune-mediated Hemolytic Anemias and Hereditary Anemias Due to Red Blood Cell Membrane and Enzyme Defects

from Section 1 - General and Non-neoplastic Hematopathology

Published online by Cambridge University Press: 01 October 2026

Maria A. Proytcheva

Edited by

Maria A. Proytcheva and

Robert B. Lorsbach

Show author details

Maria A. Proytcheva: Affiliation:
University of Arizona, College of Medicine
Robert B. Lorsbach: Affiliation:
Cincinnati Children’s Hospital Medical Center

Book contents

Get access

Summary

Hemolysis is the destruction of red blood cells (RBCs) or reduction of their lifespan. It can be categorized in several ways depending on the site of hemolysis (intravascular or extravascular), whether it is extrinsic or intrinsic to the red cell, immune or non-immune mediated, and acquired or inherited. Hemolytic anemia occurs when the RBC destruction exceeds the bone marrow proliferative capacity. This chapter focuses on the pathogenesis and diagnostic workup of the most frequent hemolytic anemias occurring in children.

Keywords

hemolytic anemia autoimmune alloimmune warm autoimmune hemolytic anemia cold agglutinins paroxysmal cold hemoglobinuria (PCH)drug-induced hemolytic anemia hemolytic disease of the fetus and newborn (HDFN)thrombotic microangiopathy (TMA)hemolytic uremic syndrome (HUS)thrombotic thrombocytopenia purpura (TTP)paroxysmal nocturnal hemoglobinuria (PNH)membrane red cell defects hereditary spherocytosis elliptocytosis stomatocytosis red blood cell enzyme defects glucose 6 phosphate deficiency (G6PD)pyruvate kinase deficiency

Information

Type: Chapter
Information: Diagnostic Pediatric Hematopathology , pp. 66 - 82
DOI: https://doi.org/10.1017/9781108861861 [Opens in a new window]
Publisher: Cambridge University Press
Print publication year: 2026

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Eder, AF. Transfusion Therapy in Autoimmune Hemolytic Anemia. In: Marques, MB, Schwartz, J, Wu, YY, editors. Transfusion Therapy: Clinical Principles and Practice, 4e. Bethesda, MD: AABB Press; 2019, 245–78.Google Scholar

di Masi, A, De Simone, G, Ciaccio, C, et al. Haptoglobin: From hemoglobin scavenging to human health. Mol Aspects Med. 2020;73:100851.10.1016/j.mam.2020.100851CrossRef Google Scholar PubMed

Borge, PD Jr, Mansfield, PM. The Positive Direct Antiglobuling Test and Immune Mediated Hemolysis. In: Cohn, CS, Delaney, M, Johnson, ST, Katz, LM, editors. Technical Manual, 20e. Bethesda, MD: AABB Press; 2020, 420–55.Google Scholar

Blackall, D, Dolatshahi, L. Autoimmune hemolytic anemia in children: Laboratory investigation, disease associations, and treatment strategies. J Pediatr Hematol Oncol. 2022;44(3):71–8.10.1097/MPH.0000000000002438CrossRef Google Scholar PubMed

Hill, QA, Stamps, R, Massey, E, et al. The diagnosis and management of primary autoimmune haemolytic anaemia. Br J Haematol. 2017;176(3):395–411.10.1111/bjh.14478CrossRef Google Scholar PubMed

Berentsen, S. New insights in the pathogenesis and therapy of cold agglutinin-mediated autoimmune hemolytic anemia. Front Immunol. 2020;11:590.10.3389/fimmu.2020.00590CrossRef Google Scholar PubMed

Leger, RM, Arndt, PA, Garratty, G. How we investigate drug-induced immune hemolytic anemia. Immunohematology. 2014;30(2):85–94.10.21307/immunohematology-2019-102CrossRef Google Scholar PubMed

Dziegiel, MH, Krog, GR, Hansen, AT, et al. Laboratory monitoring of mother, fetus, and newborn in hemolytic disease of fetus and newborn. Transfus Med Hemother. 2021;48:306–15.10.1159/000518782CrossRef Google Scholar PubMed

Risinger, M, Kalfa, TA. Red cell membrane disorders: Structure meets function. Blood. 2020;136(11):1250–61.10.1182/blood.2019000946CrossRef Google Scholar PubMed

Talarico, V, Aloe, M, Monzani, A, Miniero, R, Bona, G. Hemolytic uremic syndrome in children. Minerva Pediatr. 2016;68(6):441–55.Google Scholar PubMed

Zoja, C, Buelli, S, Morigi, M. Shiga toxin-associated hemolytic uremic syndrome: Pathophysiology of endothelial dysfunction. Pediatr Nephrol. 2010;25(11):2231–40.10.1007/s00467-010-1522-1CrossRef Google Scholar PubMed

Raina, R, Vijayvargiya, N, Khooblall, A, et al. Pediatric atypical hemolytic uremic syndrome advances. Cells. 2021;10(12):3580.10.3390/cells10123580CrossRef Google Scholar

Joly, BS, Coppo, P, Veyradier, A. Pediatric thrombotic thrombocytopenic purpura. Eur J Haematol. 2018;101(4):425–34.10.1111/ejh.13107CrossRef Google Scholar PubMed

Tarasco, E, Bütikofer, L, Friedman, KD, et al. Annual incidence and severity of acute episodes in hereditary thrombotic thrombocytopenic purpura. Blood. 2021;137(25):3563–75.10.1182/blood.2020009801CrossRef Google Scholar PubMed

Rajagopal, R, Thachil, J, Monagle, P. Disseminated intravascular coagulation in paediatrics. Arch Dis Child. 2017;102(2):187–93.10.1136/archdischild-2016-311053CrossRef Google Scholar PubMed

Witmer, CM. Hematologic manifestations of systemic disease (including iron deficiency, anemia of inflammation and DIC). Pediatr Clin North Am. 2013;60(6):1337–48.10.1016/j.pcl.2013.08.012CrossRef Google Scholar

Thachil, J. Disseminated intravascular coagulation: New pathophysiological concepts and impact on management. Expert Rev Hematol. 2016;9(8):803–14.10.1080/17474086.2016.1203250CrossRef Google Scholar PubMed

Mercuri, A, Farruggia, P, Timeus, F, et al. A retrospective study of paroxysmal nocturnal hemoglobinuria in pediatric and adolescent patients. Blood Cells Mol Dis. 2017;64:45–50.10.1016/j.bcmd.2017.03.006CrossRef Google Scholar PubMed

Brodsky, RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804–11.10.1182/blood-2014-02-522128CrossRef Google Scholar PubMed

Risitano, AM. Paroxysmal nocturnal hemoglobinuria and the complement system: Recent insights and novel anticomplement strategies. Adv Exp Med Biol. 2013;735:155–72.10.1007/978-1-4614-4118-2_10CrossRef Google Scholar PubMed

de Latour, RP, Risitano, A, Dufour, C. Severe Aplastic Anemia and PNH. In: Carreras, E, Dufour, C, Mohty, M, Kröger, N, editors. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies. Cham: Springer Copyright; 2019, 579–85.Google Scholar

Borowitz, MJ, Craig, FE, Digiuseppe, JA, et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry B Clin Cytom. 2010;78(4):211–30.Google Scholar PubMed

Lux, SE. Anatomy of the red cell membrane skeleton: Unanswered questions. Blood. 2016;127(2):187–99.10.1182/blood-2014-12-512772CrossRef Google Scholar PubMed

Mohandas, N. Inherited hemolytic anemia: A possessive beginner’s guide. Hematology Am Soc Hematol Educ Program. 2018;2018(1):377–81.Google Scholar PubMed

Kim, Y, Park, J, Kim, M. Diagnostic approaches for inherited hemolytic anemia in the genetic era. Blood Res. 2017;52(2):84–94.10.5045/br.2017.52.2.84CrossRef Google Scholar PubMed

Christensen, RD, Yaish, HM, Gallagher, PG. A pediatrician’s practical guide to diagnosing and treating hereditary spherocytosis in neonates. Pediatrics. 2015;135(6):1107–14.10.1542/peds.2014-3516CrossRef Google Scholar PubMed

Christensen, RD, Henry, E. Hereditary spherocytosis in neonates with hyperbilirubinemia. Pediatrics. 2010;125(1):120–5.10.1542/peds.2009-0864CrossRef Google Scholar PubMed

Johnson, L, Bhutani, VK, Karp, K, Sivieri, EM, Shapiro, SM. Clinical report from the pilot USA Kernicterus Registry (1992 to 2004). J Perinatol. 2009;29(Suppl. 1):S25–45.10.1038/jp.2008.211CrossRef Google Scholar PubMed

Farias, MG. Advances in laboratory diagnosis of hereditary spherocytosis. Clin Chem Lab Med. 2017;55(7):944–8.10.1515/cclm-2016-0738CrossRef Google Scholar PubMed

Bolton-Maggs, PH, Langer, JC, Iolascon, A, Tittensor, P, King, MJ. Guidelines for the diagnosis and management of hereditary spherocytosis: 2011 update. Br J Haematol. 2012;156(1):37–49.10.1111/j.1365-2141.2011.08921.xCrossRef Google Scholar PubMed

Warang, P, Gupta, M, Kedar, P, Ghosh, K, Colah, R. Flow cytometric osmotic fragility: An effective screening approach for red cell membranopathies. Cytometry B Clin Cytom. 2011;80(3):186–90.Google Scholar PubMed

Ciepiela, O, Adamowicz-Salach, A, Zgodzińska, A, Łazowska, M, Kotuła, I. Flow cytometric osmotic fragility test: Increased assay sensitivity for clinical application in pediatric hematology. Cytometry B Clin Cytom. 2018;94(1):189–95.10.1002/cyto.b.21511CrossRef Google Scholar PubMed

Joshi, P, Aggarwal, A, Jamwal, M, et al. A comparative evaluation of eosin-5’-maleimide flow cytometry reveals a high diagnostic efficacy for hereditary spherocytosis. Int J Lab Hematol. 2016;38(5):520–6.10.1111/ijlh.12533CrossRef Google Scholar PubMed

Da Costa, L, Galimand, J, Fenneteau, O, Mohandas, N. Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders. Blood Rev. 2013;27(4):167–78.10.1016/j.blre.2013.04.003CrossRef Google Scholar PubMed

King, M-J, Behrens, J, Rogers, C, et al. Rapid flow cytometric test for the diagnosis of membrane cytoskeleton-associated haemolytic anaemia. Br J Haematol. 2000;111(3):924–33.Google Scholar PubMed

Girodon, F, Garçon, L, Bergoin, E, et al. Usefulness of the eosin-5’-maleimide cytometric method as a first-line screening test for the diagnosis of hereditary spherocytosis: comparison with ektacytometry and protein electrophoresis. Br J Haematol. 2008;140(4):468–70.10.1111/j.1365-2141.2007.06944.xCrossRef Google Scholar PubMed

Alper, SL. Genetic diseases of PIEZO1 and PIEZO2 dysfunction. Curr Top Membr. 2017;79:97–134.Google Scholar PubMed

Glucose-6-phosphate dehydrogenase deficiency. WHO Working Group. Bull World Health Organ. 1989;67(6):601–11.Google Scholar

Nannelli, C, Bosman, A, Cunningham, J, Dugué, PA, Luzzatto, L. Genetic variants causing G6PD deficiency: Clinical and biochemical data support new WHO classification. Br J Haematol. 2023;202(5):1024–32.10.1111/bjh.18943CrossRef Google Scholar PubMed

Accessibility standard: Inaccessible, or known limited accessibility

Why this information is here

This section outlines the accessibility features of this content - including support for screen readers, full keyboard navigation and high-contrast display options. This may not be relevant for you.

Accessibility Information

The HTML of this chapter is known to have missing or limited accessibility features. We may be reviewing its accessibility for future improvement, but final compliance is not yet assured and may be subject to legal exceptions. If you have any questions, please contact accessibility@cambridge.org.

Content Navigation

Table of contents navigation
Allows you to navigate directly to chapters, sections, or non‐text items through a linked table of contents, reducing the need for extensive scrolling.

Index navigation
Provides an interactive index, letting you go straight to where a term or subject appears in the text without manual searching.

Reading Order & Textual Equivalents

Single logical reading order
You will encounter all content (including footnotes, captions, etc.) in a clear, sequential flow, making it easier to follow with assistive tools like screen readers.

Visualised data also available as non-graphical data
You can access graphs or charts in a text or tabular format, so you are not excluded if you cannot process visual displays.

Visual Accessibility

Use of high contrast between text and background colour
You benefit from high‐contrast text, which improves legibility if you have low vision or if you are reading in less‐than‐ideal lighting conditions.