G6PD Deficiency Flashcards
G6PD Deficiency
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red blood cell enzyme defect. It is more common in people from the Mediterranean and Africa and is inherited in a X-linked recessive fashion. Many drugs can precipitate a crisis as well as infections and broad (fava) beans
Pathophysiology
↓ G6PD → ↓ glutathione → increased red cell susceptibility to oxidative stress
G6PD Deficiency - Features
Features neonatal jaundice is often seen intravascular haemolysis gallstones are common splenomegaly may be present Heinz bodies on blood films
G6PD Deficiency - Diagnosis
Diagnosis is made by using a G6PD enzyme assay
G6PD Deficiency - Drugs thought to cause Haemolysis
Some drugs causing haemolysis anti-malarials: primaquine ciprofloxacin sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas nitrofurantoin
G6PD Deficiency - Abx thought to be safe
Antibiotics thought to be safe penicillins cephalosporins macrolides tetracyclines trimethoprim
Basically all except Ciprofloxacin, Sulphonamide abx except trimethoprim and antimalarials primaquine
Comparing G6PD Deficiency to Hereditary Spherocytosis
Gender
G6PD = Male (X-linked recessive)
HS = Male + female (autosomal dominant)
Ethnicity
G6PD = African + Mediterranean descent
HS = Northern European descent
Typical history G6PD: • Neonatal jaundice • Infection/drugs precipitate haemolysis • Gallstones
HS: • Neonatal jaundice • Chronic symptoms although haemolytic crises may be precipitated by infection • Gallstones • Splenomegaly is common
Blood film
G6PD = Heinz bodies
HS = Spherocytes (round, lack of central pallor)
Diagnostic test
G6PD = Measure enzyme activity of G6PD HS = Osmotic fragility test
G6PD and Primaquine - Example Question
A 24 year-old medical student of Italian extraction returns from elective in India. One week after his return he presents with fever, headache, and myalgia.
Investigations are as follows:
Hb 10.1 g/dl MCV 101.2 fl Platelets 43 x10^9/l WCC 6.1 x10^9/l Na 134mmol/l K 4.6 mmol/l Urea 3.8 mmol/l Creatinine 80 mol/l ALT 44 IU/l ALP 78 IU/l Bilirubin 33 mol/l Albumin 38 g/l Thick and thin blood films Plasmodium ovale parasites with red cells
What other blood test will be essential for the management of this condition?
Coomb's test > G6PD enzyme assay Chloroquine resistance test Ham's test Reticuloctye count
The life cycle of Plasmodium ovale includes a dormant phase of liver hypnozoites, which may give rise to a new wave of parasitaemia after conventional treatment which targets only erythrocytic forms. Eradication of liver hypnozoites with primaquine is essential to prevent delayed relapse of infection.
Primaquine can precipitate haemolysis in individuals with G6PD (glucose-6-phosphate dehydrogenase) deficiency. G6PD activity should be tested before commencing treatment. If deficient, expert advice should be sought.
Coomb’s test, also known as the direct antiglobulin test (DAT), detects antibody bound to the surface of red cells and is a test for autoimmune haemolytic anaemia. A variable degree of haemolysis occurs in malaria, but is not typically autoimmune. Rather it is due predominantly to destruction of infected red cells during parasite replication and breakdown in the spleen.
Chloroquine is the first-line treatment for non-falciparum malaria. Chloroquine resistance in Plasmodium ovale and malariae is extremely rare, but has been reported for vivax. Chloroquine is inadequate for the treatment of falciparum malaria as resistance is widespread.
Ham’s test was previously used for the diagnosis of paroxysmal nocturnal haemoglobinuria, a condition which causes intravascular haemolysis.
Reticulocytes are red cell precursors, which are prematurely released from the marrow in response to haemolysis. Their large size accounts for the macrocytosis which often accompanies haemolytic anaemia. An elevated reticulocyte count is an appropriate response to haemolysis in the presence of an adequately functioning bone marrow.
Haemolytic Crisis in G6PD Deficiency - Example Question
A 51-year-old man presents with dysuria and a low grade fever. He is prescribed a course of Nitrofurantoin for a suspected urinary tract infection. He has a history of ischaemic heart disease for which he takes aspirin and atorvastatin. The following day, he notices that his urine has become very dark and he feels breathless and more unwell.
Bloods show:
Hb 78 g/L WCC 14.1 x 10^9/L Neutrophils 13 x 10^9/L Platelets 280 x 10^9/L Bilirubin 87 mg/dL ALT 45 IU/L Alkaline phosphatase 73 IU/L Urea 5 mmol/L Creatinine 80 µmol/L
Blood film microscopy comments on the presence of Heinz bodies. What is the underlying diagnosis?
Hereditary spherocytosis Paroxysmal nocturnal haemoglobinuria Haemolytic uraemic syndrome Urinary sepsis secondary to E. coli > Glucose-6-phosphate dehydrogenase deficiency (G6PD)
The blood tests reveal anaemia with a bilirubin rise, which indicates haemotlyic anaemia. Heinz bodies are red cell inclusions consisting of denatured Hb; they are a feature of oxidative stress. Nitrofurantoin is one of many drugs that can cause haemolytic crisis in G6PD deficiency. Heinz bodies would not usually be seen on the blood films of the other conditions.
