Show Summary Details
Page of

Haemolytic anaemia—congenital and acquired 

Haemolytic anaemia—congenital and acquired

Haemolytic anaemia—congenital and acquired

Amy Powers

, Leslie Silberstein

, and Frank J. Strobl

Page of

PRINTED FROM OXFORD MEDICINE ONLINE ( © Oxford University Press, 2015. All Rights Reserved. Under the terms of the licence agreement, an individual user may print out a PDF of a single chapter of a title in Oxford Medicine Online for personal use (for details see Privacy Policy).

date: 29 April 2017

Premature destruction of red cells occurs through two primary mechanisms: (1) decreased erythrocyte deformability that leads to red-cell sequestration and extravascular haemolysis in the spleen and other components of the reticuloendothelial system—may be caused by membrane defects, metabolic abnormalities, exogenous oxidizing agents, or pathological antibodies; (2) red-cell membrane damage and intravascular haemolysis—may be caused by exposure to pathological antibodies, activated complement, mechanical forces, chemicals, and infectious agents.

Clinical features—general aspects

These include (1) increased red cell production—manifestations include reticulocytosis, polychromasia, macrocytosis, erythroid hyperplasia, and bone changes; (2) increased red-cell destruction—features include decreased haemoglobin levels, fragmented red cells, decreased haptoglobin levels, increased unconjugated bilirubin levels, increased plasma LDH levels, haemoglobinaemia, haemoglobinuria, haemosiderinuria, splenomegaly.

Congenital disorders of the red-cell membrane

Hereditary spherocytosis—usually an autosomal dominant condition due to defects in α‎- or β‎-spectrin, or the proteins that bind spectrin to the plasma membrane. Presentation is typically in childhood with anaemia, jaundice, and splenomegaly, with red cells demonstrating increased osmotic fragility. Anaemia can be corrected in almost all cases by splenectomy. See also Chapter 22.5.10.

Hereditary elliptocytosis—a genetically heterogeneous disorder caused in most cases by defects in both α‎-spectrin and β‎-spectrin that interfere with spectrin self-association. Less than 10% of cases exhibit significant haemolysis, but the peripheral blood smear contains elliptocytes, ‘pencil cells’, and other abnormally shaped red cells. Asymptomatic individuals require no treatment; patients who are symptomatic often obtain some benefit from splenectomy. See also Chapter 22.5.10.

Other disorders—these include hereditary pyropoikilocytosis, hereditary spherocytic elliptocytosis, hereditary stomatocytosis, and hereditary xerocytosis.

Congenital disorders of red-cell enzymes

Glucose-6-phosphate dehydrogenase (G6PD) deficiency—an X-linked, recessive disorder that is maintained in populations because it confers some resistance to Plasmodium falciparum infection. Causes little to no haematological abnormality under normal circumstances, but severe haemolysis and anaemia occur during periods of oxidant stress that may be caused by chemicals, drugs, infectious agents, and the bean Vicia faba (favism). Diagnosis depends on the demonstration of decreased red-cell G6PD activity, for which there is a rapid fluorescent screening assay. Management involves avoidance of precipitants, with blood transfusion required during severe haemolytic episodes. See also Chapter 22.5.12.

Pyruvate kinase deficiency—an autosomal recessive condition, with severe deficiency causing haemolysis, anaemia and jaundice throughout life, eventually resulting in splenomegaly, gallstones, and aplastic anaemia. See Chapter 22.5.11 for further discussion.

Acquired immune haemolytic anaemias

Immune haemolysis may occur when IgG, IgM, or IgA antibodies and/or complement bind to the erythrocyte surface. The direct antiglobulin test (DAT) or direct Coombs’ test detects the presence of IgG antibody or complement on the red-cell surface: IgM and IgA antibodies are not directly detectable with standard testing reagents.

Autoimmune haemolytic anaemias (HA)—these are best classified according to the temperature at which the antibody optimally binds to the erythrocyte. (1) Warm autoimmune HA—typically IgG; symptomatic patients present with anaemia, jaundice, and splenomegaly; associated with lymphoid malignancies; first-line treatment is with corticosteroids. (2) Cold agglutinin syndrome—autoantibodies are typically IgM and are most active at low temperatures; seen in younger patients following infection with Mycoplasma pneumoniae or infectious mononucleosis and in older patients in association with lymphoma, chronic lymphocytic leukaemia, or Waldenström macroglobulinaemia. (3) Paroxysmal cold haemoglobinuria. (4) Mixed type autoimmune HA—both IgG and complement are present on the red cells; may be idiopathic or secondary (most often to systemic lupus erythematosus). (5) Drug induced—haemolysis can be caused by drugs that induce a positive direct antiglobulin test by (a) acting as a drug hapten, (b) immune complex formation, (c) autoantibody production.

Alloimmune HA—these include (1) acute haemolytic transfusion reactions—may begin after the infusion of as little as 10 ml of incompatible blood, with symptoms and signs including chest or flank pain, nausea, vomiting, fever, chills, hypotension, respiratory distress, and haemoglobinuria. Despite immediate stopping of the transfusion and optimal supportive care, patients can develop renal failure, disseminated intravascular coagulation, and even die. (2) Other conditions—these include delayed haemolytic transfusion reactions, passenger lymphocyte haemolysis, haemolytic disease of the newborn (caused by rhesus (Rh) D incompatibility or ABO incompatibility).

Acquired nonimmune haemolytic anaemias

Common or important causes include (1) infections—e.g. malaria, babesiosis; (2) drugs and chemicals—e.g. nitrofurantoin; (3) mechanical—e.g. incompetent prosthetic heart valves; microangiopathic haemolytic anaemia (MAHA), which describes a spectrum of disorders including haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura that are characterized by mechanical destruction of red cells resulting from thrombi that occlude the microvasculature.

Access to the complete content on Oxford Medicine Online requires a subscription or purchase. Public users are able to search the site and view the abstracts for each book and chapter without a subscription.

Please subscribe or login to access full text content.

If you have purchased a print title that contains an access token, please see the token for information about how to register your code.

For questions on access or troubleshooting, please check our FAQs, and if you can't find the answer there, please contact us.