Haemolytic Anaemias
Pathophysiology
Haemolysis is the process of red cell breakdown. It can be due to intrinsic problems of the red blood cell, or extrinsic factors such as antibodies and mechanical obstruction shearing red blood cells in blood vessels.1
Causes
Hereditary Spherocytosis
Hereditary Spherocytosis is an Autosomal dominant inheritable condition. It is due to abnomral spectrin (a protein found in the membrane of red blood cells). These abnormal RBCs are more prone to destruction in the spleen. It presents with clinical features of jaundice and splenomegaly. Peripheral blood film shows spherocytes (circular RBCs, with less or no central pallor). As this is not an immune mediated disease, the direct antiglobulin test is negative. A special test where the osmotic fragility of the red blood cells is measured shows increased fragility. Management involves folic acid and splenectomy in some cases.1
Clinical Features Haemoglobinopathies: Thalassaemia and Sickle cell disease
Visit our Thalassaemia and Sickle Cell Disease pages for more information.
G6PD deficiency
The G6PD enzyme helps protect RBCs from oxidant stress. If deficient, when there is oxidant stress, there is severe haemolytic anaemia. This is an X-Linked (males more affected, females are carriers) recessive disease. People with G6PD deficiency are asymptomatic until exposed to a trigger of oxidative stress, which then results in haemolytic anaemia.
Triggers:
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Fava beans
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Drugs – anti-malarials
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Infection
Investigations include Enzyme Assay (not during acute crisis) which will show low levels of the enzyme. Treatment is to stop the offending trigger. Blood transfusion may be required as supportive care.1
Pyruvate Kinase deficiency
This is an acquired Autosomal Recessive disorder where RBCs can’t make enough ATP so they become rigid.
Clinical Features include variable levels of jaundice (mild symptoms). It is also investigated with enzyme assays. If anaemia is severe and causing symptoms, red cell transfusions can be given as supportive care. Occasionally treatment with splenectomy is required.1
Autoimmune Haemolytic Anaemia (AIHA)
Autoimmune haemolytic anaemia is when the body produces antibodies against its own red blood cells. it is classified into 2 types based on the type of antibody involved. Warm antibodies occur at temperatures >37oC, and cold antibodies occur in temperatures <37oC. Management depends on the type of antibody, and is aimed at the underlying cause.1
Haemolytic disease of the newborn: ABO Incompatible/Rhesus incompatibility
In haemolytic disease of the newborn, the mom's body has formed antibodies in response to the baby's red blood cell antigens. As a result, the antibodies attack the baby's red blood cells and cause haemolytic disease.
Rhesus incompatibility occurs when the mother is Rh -ve. The baby inherits the Rh antigen from the father. During delivery, maternal blood is exposed to fetal blood and forms antibodies against the baby's Rh antigen in response to thinking it is foreign. It takes time for these antibodies to develop so it generally does not affect the first pregnancy. However, these antibodies remain in the mother's blood so if they become pregnant again, these antibodies will cross the placenta and attack the red blood cells of the baby.3
This is prevented by screening all pregnant women for their ABO and Rh status when they come for booking appointments. The screening test is the INDIRECT COOMBS TEST which uses antibodies in the laboratory to detect anti-D antibodies in maternal blood. If they are Rh-ve, they will get anti-D from week 28 of their pregnancy.1 Anti-D works by binding to the baby's Rh+ red blood cells, thereby "mopping them up" and preventing the mother's blood from exposure to the Rh antigen, so that it will not produce any antibodies.3
ABO incompatible disease is very similar, but presents with less severe haemolysis than Rh incompatible disease.
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The maternal and foetal circulations are usually kept separate by the placental barrier
Mechanical haemolysis
Several pathologies can cause a mechanical destruction of passing red blood cells. Mechanical cardiac valves or diseases valves can interrupt smooth flow of blood and damage blood vessels in the process. In smaller blood vessels, the build up of fibrin meshes can trap and destroy red blood cells - this occurs in DIC. A similar thing happens due to platelet rich thrombi in thrombotic thrombocytopenic purpura (TTP).1,2
Clinical Features of Haemolytic Anaemias
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Symptoms of anaemia
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Symptoms/signs due to increased red cell breakdown:
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Increased bilirubin leads to jaundice
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If spleen is the site of red cell destruction, they may have splenomegaly
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Prolonged haemolytic anaemia in children can lead to marrow expansion --> skeletal abnormalities such as frontal bossing of the skull
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Pigment gallstones1,2
Investigations
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Full blood count
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Peripheral blood film - reticulocytes
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Reticulocyte count
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Raised serum bilirubin, LDH, urobilinogen
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Decreased haptoglobin
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haptoglobin is a scavenger protein which binds to free haem released from lysed red blood cells, so its concentration will decrease in the blood
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Enzyme assays for PK and G6PD deficiencies
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Direct Autoantibody Test (Coomb’s Test) will be positive in autoimmune haemolytic anaemias
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these antibodies bind to the antibodies on the surface of the red blood cells and therefore are only positive if the cause of haemolysis is autoimmune1,2
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References
1. Mehta AB, Hoffbrand AV. Haematology at a Glance. 4th ed.: John Wiley & Sons; 2014.
2. Knott L. Haemolytic Anaemia [Internet]. Patient UK. 2015 [cited 11 March 2020]. Available from: https://patient.info/doctor/haemolytic-anaemia
3. Moise K. Management of rhesus alloimmunization in pregnancy. Obstetrics & Gynecology. 2002;100(3):600-611.