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Figure 12.26 Abbreviated pathways of anaerobic glycolysis (Embden-Meyerhof) and hexose monophosphate (HMP) shunt in the metabolism CHAPTER 12
of erythrocyte. The two red cell enzyme defects, glucose-6 phosphate dehydrogenase (G6PD) and pyruvate kinase, are shown bold.

in oxidation and precipitation of haemoglobin within the PK DEFICIENCY
red cells forming Heinz bodies. Besides G6PD deficiency, Pyruvate kinase (PK) deficiency is the only significant
deficiency of various other enzymes involved in the hexose enzymopathy of the Embden-Meyerhof glycolytic
monophosphate shunt may also infrequently cause clinical pathway.The disorder is inherited as an autosomal recessive
problems. pattern. Heterozygote state is entirely asymptomatic, while
CLINICAL FEATURES. The clinical manifestations are those the homozygous individual presents during early childhood
of an acute haemolytic anaemia within hours of exposure to with anaemia, jaundice and splenomegaly.
oxidant stress. The haemolysis is, however, self-limiting even
if the exposure to the oxidant is continued since it affects the LABORATORY FINDINGS: These are as under:
older red cells only. Haemoglobin level may return to normal 1. Normocytic and normochromic anaemia.
when the older population of red cells has been destroyed 2. Reticulocytosis.
and only younger cells remain. Some patients may have only 3. Blood film shows bizarre red cells.
darkening of the urine from haemoglobinuria but more 4. Osmotic fragility is usually normal but after incubation
severely affected ones develop constitutional symptoms it is increased.
including jaundice. Treatment is directed towards the 5. Autohaemolysis is increased, but unlike hereditary Introduction to Haematopoietic System and Disorders of Erythroid Series
prevention of haemolytic episodes such as stoppage of spherocytosis, is not corrected by addition of glucose.
offending drug. Blood transfusions are rarely indicated. 6. Direct specific enzyme assay on red cells is the only
method of establishing the diagnosis.
LABORATORY FINDINGS. These are as under:
1.During the period of acute haemolysis, there is rapid Haemoglobinopathies
fall in haematocrit by 25-30%, features of intravascular Haemoglobin in RBCs may be abnormally synthesised due
haemolysis such as rise in plasma haemoglobin, to inherited defects. These disorders may be of two types:
haemoglobinuria, rise in unconjugated bilirubin and fall Qualitative disorders in which there is structural
in plasma haptoglobin. Formation of Heinz bodies is abnormality in synthesis of haemoglobin e.g. sickle cell
visualised by means of supravital stains such as crystal syndrome, other haemoglobinopathies.
violet, also called Heinz body haemolytic anaemia. However, Quantitative disorders in which there quantitatively
Heinz bodies are not seen after the first one or two days decreased globin chain synthesis of haemoglobin e.g.
since they are removed by the spleen, leading to formation thalassaemias.
of ‘bite cells’ and fragmented red cells. Both these groups of disorders may occur as homozygous
2. Between the crises, the affected patient generally has state in which both genes coding for that character are
no anaemia. The red cell survival is, however, shortened. abnormal, or heterozygous when one gene is abnormal and
The diagnosis of G6PD enzyme deficiency is made by the other gene is normal. However, there are examples of
one of the screening tests (e.g. methaemoglobin reduction combined disorders too in which there are two different
test, fluorescent screening test, ascorbate cyanide mutations in loci of two corresponding genes (i.e. double
screening test), or by direct enzyme assay on red cells. heterozygous) e.g. HbS gene from one parent and β-thal from
S thal
the other parent resulting in β β . These disorders may vary