Recognise inherited vulnerability to oxidative haemolysis, remove precipitating infections, foods and medicines, interpret enzyme testing at the correct time and prevent recurrent and neonatal harm.
G6PD catalyses the first step of the pentose phosphate pathway, producing NADPH that keeps glutathione reduced. Mature red cells depend on this system to neutralise oxidants. Variants that reduce enzyme activity leave haemoglobin and membrane proteins vulnerable during infection, fava-bean exposure or treatment with certain oxidant medicines. Denatured haemoglobin precipitates as Heinz bodies; splenic macrophages remove affected membrane to create bite cells, while more severe injury causes intravascular rupture, haemoglobinuria and renal stress.
Inheritance is X linked, but sex alone cannot exclude disease. Hemizygous males generally express one variant, while heterozygous females have a mosaic red-cell population and can range from unaffected to clinically significant deficiency. Prevalence is higher in people with African, Mediterranean, Middle Eastern and parts of Asian ancestry, reflecting historic malaria selection, yet ancestry guides suspicion rather than diagnosis. Neonates may develop important hyperbilirubinaemia, and rare severe variants cause chronic non-spherocytic haemolytic anaemia rather than episodic disease.
Pathogenic G6PD variants reduce enzyme stability or activity; hemizygous males are often more consistently affected, while lyonisation creates variable expression in heterozygous females.
Bacterial and viral infections generate oxidants and inflammatory stress, making acute illness a common precipitant of haemolysis in susceptible red cells.
Rasburicase, dapsone, primaquine and other agents identified in current BNF or product guidance can exceed red-cell antioxidant capacity.
Fava beans classically trigger favism, while diabetic ketoacidosis and other severe physiological stressors may contribute alongside infection or medicine exposure.
Reduced pentose-phosphate-pathway enzyme activity limits red-cell NADPH production because mature erythrocytes lack alternative organelle-based antioxidant systems.
Insufficient NADPH prevents efficient regeneration of reduced glutathione, allowing hydrogen peroxide and other oxidants to accumulate during stress.
Denatured haemoglobin forms Heinz bodies and membrane proteins become rigid, fragile and susceptible to intravascular rupture or splenic removal.
Older enzyme-poor erythrocytes are destroyed first, leaving younger reticulocytes with higher residual activity and temporarily altering the measured enzyme result.
Jaundice, pallor, dark urine, fatigue and back or abdominal pain beginning after infection, fava beans or a recognised medicine suggests triggered haemolysis.
Bite cells, blister cells, polychromasia and specialist supravital Heinz-body staining support oxidant injury but vary with sampling time.
Haemoglobinuria, rapid haemoglobin fall, rising creatinine, oliguria, hyperkalaemia, chest pain or syncope indicates organ-threatening haemolysis and urgent support.
Early or rapidly rising jaundice in a baby with relevant ancestry or family history raises G6PD-related hyperbilirubinaemia and requires urgent bilirubin management.
A woman with a convincing trigger-dependent phenotype may have clinically important mosaic deficiency despite an intermediate or apparently normal screening result.
Persistent jaundice, anaemia, splenomegaly, gallstones and reticulocytosis without a discrete trigger suggests a rarer chronic non-spherocytic haemolytic phenotype.
Spherocytes and a positive DAT support immune coating, whereas oxidant exposure, bite or blister cells and a negative DAT favour G6PD-related injury.
Heinz bodies and episodic oxidative haemolysis also occur with unstable haemoglobin variants, requiring haemoglobin and genetic investigation when enzyme testing is normal.
Lifelong jaundice, splenomegaly, family history, spherocytes and membrane-test abnormalities suggest chronic membrane loss rather than trigger-dependent oxidant episodes.
Schistocytes, thrombocytopenia and neurological, renal or cardiac injury indicates fragmentation and requires urgent TTP or secondary-microangiopathy assessment.
Pyruvate kinase and rarer red-cell enzyme disorders can cause DAT-negative inherited haemolysis, often with a more chronic phenotype and different assay pattern.
Rapid intravascular and extravascular destruction can cause syncope, cardiac strain, shock or critical oxygen-delivery failure, particularly with continuing oxidant exposure.
Filtered free haemoglobin, dehydration and haemodynamic compromise can damage renal tubules during brisk intravascular haemolysis episodes.
Accelerated bilirubin production with immature neonatal clearance can cause severe jaundice and bilirubin encephalopathy without timely surveillance and treatment.
Failure to communicate the diagnosis and check future medicines exposes patients repeatedly to preventable haemolysis, hospital admission and transfusion.
Rare severe variants cause ongoing destruction, jaundice, splenomegaly, gallstones, folate demand and transfusion burden rather than isolated triggered attacks.
Reticulocytes contain more residual enzyme than older cells. Selective destruction during a crisis enriches the sample with cells that can mask deficiency.
Random X-chromosome inactivation creates a spectrum of enzyme activity, so sex and a single screening result cannot overrule a convincing phenotype.
A new medicine may attract attention, but inflammatory oxidative stress from the illness itself can be the principal precipitant or act synergistically.
Macrophages remove Heinz-body-containing membrane, leaving semicircular defects. The precipitated haemoglobin may already be gone when the routine film is examined.
Medicine risk depends on dose, indication and evidence. The live BNF and product information are safer than an inherited photocopied avoidance list.
Excluding G6PD deficiency because the patient is female.
Accepting normal enzyme activity during brisk acute haemolysis as definitive.
Continuing a plausible oxidant medicine while waiting for confirmation.
Calling every DAT-negative haemolysis G6PD deficiency without film and exposure evidence.
Giving rasburicase before assessing G6PD risk when the clinical timeline allows testing.
Using an outdated universal medicine list instead of current BNF and product guidance.
Failing to communicate family risk and neonatal jaundice planning.
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A man develops jaundice, dark urine, bite cells and falling haemoglobin after starting a recognised oxidant medicine. He is haemodynamically stable. What is the best immediate plan?
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.
Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes
The SmPC contraindicates use in G6PD deficiency because severe haemolysis and methaemoglobinaemia can occur. Assess higher-risk ancestry before treatment when feasible, stop immediately if either reaction develops and seek urgent specialist care rather than reflexively using methylene blue, which may worsen haemolysis in G6PD deficiency.
Check vitamin B12 status before prolonged use and avoid routine indefinite prescribing after a single brief episode. Continued haemolysis needs specialist diagnosis, gallstone and transfusion review.