Loss of NADPH leaves red cells defenceless against oxidative stress
Expansion
Mechanism: G6PD is the first and rate limiting enzyme of the pentose phosphate pathway, generating NADPH. In the red cell, NADPH maintains reduced glutathione, the only defence against oxidative stress, since red cells have no mitochondria and no alternative source.
Inheritance: X-linked recessive, so mainly affecting males. It is the commonest enzymopathy worldwide, protecting against falciparum malaria, and is common in African, Mediterranean, Middle Eastern and South East Asian populations.
Triggers, causing acute intravascular haemolysis
- Drugs: primaquine and other antimalarials, sulphonamides and co-trimoxazole, nitrofurantoin, dapsone, quinolones, methylene blue, high dose aspirin
- Fava beans (favism)
- Infection, which is the commonest trigger of all
- Naphthalene (mothballs)
Findings: anaemia, jaundice, dark urine, Heinz bodies (denatured haemoglobin, seen on supravital stain), and bite cells and blister cells where splenic macrophages have removed them.
“Test after the storm, not during it.” During haemolysis the oldest, most deficient cells have already lysed and the reticulocytes remaining have higher enzyme activity, giving a falsely normal level. Retest several weeks later.
Management is avoidance of triggers; transfusion is rarely needed, and neonates may need phototherapy or exchange transfusion for jaundice.