Inherited and acquired haemolytic anaemias Dr. Suhair Abbas Ahmed

Hereditary haemolytic anaemias Membrane defects – congenital spherocytosis Metabolic defects – G6PD enzyme deficiency Haemoglobin defects Qualitative defects – sickle cell anaemia Quantitative defects – Thalassaemia

Hereditary spherocytosis South East Asian ovalocytosis Membrane defects Hereditary spherocytosis South East Asian ovalocytosis

Hereditary spherocytosis (HS) It is the most common hereditary haemolytic anaemia in North Europeans.

Pathogenesis of HS It is caused by a defect in the proteins involved in the interactions between the membrane cytoskeleton and the lipid bilayer of the red cell. ( ankyrin, spectrin and pallidin).

Clinical features The inheritance is autosomal dominant. Rarely it may be autosomal recessive. The anaemia may present at any age from infancy to old age. Jaundice is fluctuating. Splenomegaly occurs in most of the patients. Pigment gall stones are frequent.

Haematological findings in HS Anaemia is usual. Reticulocytosis 5-20% Microsherocytes are seen in the blood film. (densely staining with smaller diameters than normal red cells).

Reticulocytosis Reticulocytosis is a feature of increased red cell production. New methylene blue is used to stain the reticulocytes

Other investigations The classic finding is that the osmotic fragility is increased. Autohaemolysis is increased and corrected by glucose. Direct antiglobulin test is normal.

Autohaemolysis test in HS There is increased haemolysis in the patient in comparison with the control. Glucose has given partial correction.

Treatment The principal form of treatment is splenectomy although this should not be performed unless clinically indicated because of the risk of post-splenectomy sepsis, particularly in early childhood. Folic acid is given in severe cases.

South-East Asian ovalocytosis This is common in Malaysia, Indonesia and the Philippines. It is due to Band 3 protein abnormality. The cells are rigid and resist invasion by malaria parasite. Most cases are asymptomatic.

Blood film in hereditary stomato-ovalocytosis basophilic stippling and numerous stomatocytes.

Defective red cell metabolism G6PD enzyme deficiency Pyruvate kinase deficiency

G6PD functions to reduce nicotinamide adenine dinucleotide phosphate (NADPH) while oxidizing glucose-6-phosphate. NADPH is needed for the production of reduced glutathione (GSH) which is important to defend the red cells against oxidant stress.

G6PD deficiency More than 400 variants due to point mutations or deletions of the enzyme G6PD have been characterized which show less activity than normal. Worldwide over 400 million people are G6PD deficient in enzyme activity.

Clinical features G6PD deficiency is usually asymptomatic. Neonatal jaundice. Acute haemolytic anaemia in response to oxidant stress: drugs, fava beans or infections.

G6PD deficiency The inheritance is sex-linked, affecting males, and carried by females. The main races affected are in West Africa, the Mediteranean, the Middle East, and South East Asia.

Diagnosis Between crises blood count is normal. The enzyme deficiency is detected by One of a number of screening tests or By direct enzyme assay on red cells. During the crisis, the blood film may show contracted and fragmented cells, bite and blister cells. Enzyme assay may give a false normal level in the phase of acute haemolysis. There are feaures of intravascular haemolysis.

G6PD deficiency The blood film shows irregularly contracted cells [deep red arrows] and sometimes hemighosts [deep blue arrow] in which all the haemoglobin appears to have retracted to one side of the erythrocyte.

Treatment The offending drug is stopped. Any underlying infection is treated. Blood transfusion, if necessary, for severe anaemia.

Defective haemoglbin Sickle cell anaemia

Defective haemoglobin Sickle cell anaemia It results from single base change in the DNA coding for the amino acid in the sixth position in the b-globin chain. This leads to an amino acid change from glutamic acid to valine HbS will be formed instead of the normal Hb.

Sickle cell anaemia Hb S is insoluble and forms crystals when exposed to low oxygen tension. Deoxygenated sickle Hb polymerizes into long fibrils. The red cells sickle and may block the different areas of the microcirculation or large vessels causing infarcts of various organs. It is widespread in Africa.

Laboratory findings Hb is usually 6-9 g/dl. Sickle cells and target cells occur in the blood. Screening tests for sickling are positive. Hb electrophoresis in Hb SS, no Hb A is detected. The amount of Hb F is variable 5-15%.

Sickle cell anaemia Sickle cells in sickle cell disease.