Red Cell Enzyme Defects ✅ Flashcards
What is the most common red cell enzyme deficiency causing haemolytic anaemia?
Glucose-6-phosphate dehydrogenase (G6PD)
What does G6PD protect against?
Protects the cell from oxidative damage
What does G6PD do?
Catalyses the first step of the pentose phosphate pathway, regulating the rate of the pathway
What is the inheritance of G6PD deficiency?
X-linked
What is the result of G6PD deficiency being a X-linked disorder?
It predominantly affects boys, although female carriers may be mildly affected
Who is G6PD deficiency most prevalent in?
Patients of African, Mediterranean, or Asian origin
Are patients with G6PD deficiency always symptomatic?
No, majority of patients are asymptomatic most of the time, although some rare mutations can cause chronic haemolytic anaemia
What is one of the most common presentations of G6PD deficiency?
Neonatal jaundice
Is the neonatal jaundice caused by G6PD deficiency severe?
Potentially, can be severe enough to cause kernicterus
What is thought to be the cause of the jaundice in G6PD deficiency?
Liver dysfunction, rather than haemolysis
What blood results support the theory that the jaundice in G6PD deficiency is predominantly due to liver dysfunction rather than haemolysis?
Despite marked hyperbilirubinaemia, the Hb is usually normal or very slightly reduced
How does G6PD deficiency present after the neonatal period?
Usually as an acute haemolytic crisis
What can precipitate an acute haemolytic crisis in G6PD deficiency?
- Infection
- Certain drugs
- Ingesting broad beans
What will blood tests during an acute haemolytic crisis due to G6PD deficiency show?
- Reduced Hb
- Raised reticulocytes
- Hyperbilirubinaemia
- Increased LDH
What will be showed on blood film in acute haemolysis caused by G6PD deficiency?
- Fragmented red cells
- ‘Bite’ cells
- Polychromasia
What can be seen on blood film in acute haemolysis caused by G6PD deficiency if special stains are used?
Heinz bodies
What are Heinz bodies?
Red cell inclusions made up of denatured Hb
What does the blood film show in G6PD deficiency between haemolytic crises?
Completely normal
Is the reticulocyte count increased in G6PD deficiency between haemolytic crises?
No
What is the treatment for G6PD deficiency?
Treatment is unnecessary apart from during severe haemolytic episodes, were red cell transfusion may be required
How is diagnosis confirmed in G6DPD deficiency?
By measuring red cell G6PD levels
When might red cell G6PD levels be falsely elevated?
During an acute crisis
What advice should be given after a diagnosis of G6PD deficiency?
Parents and children should be advised about avoiding potential triggers, and given a list of the most commonly used drugs which may precipitate acute haemolysis
How common is pyruvate kinase deficiency compared to G6PD deficiency?
Much less common
When should pyruvate kinase deficiency be considered?
In presence of family history, or after excluding G6PD deficiency
What does a deficiency of pyruvate kinase in RBCs result in?
Insufficient ATP production, leading to ‘rigid’ cells and subsequent haemolysis
How might pyruvate kinase deficiency present?
- Hydrops fetalis
- Neonatal haemolytic anaemia
- Chronic haemolytic anaemia in early childhood
Is the level of anaemia variable in pyruvate kinase deficiency?
Yes
Why is the anaemia surprisingly well tolerated in pyruvate kinase deficiency?
Because increased 2,3-DPG levels shift the O2 dissociation curve to the right
What can be required in severe causes of pyruvate kinase deficiency?
Patients can be transfusion dependent
What is the inheritance pattern of pyruvate kinase deficiency?
Autosomal recessive
What is found on the blood film in pyruvate kinase deficiency?
‘Prickle’ red cells
How can a diagnosis of pyruvate kinase deficiency be made?
Measuring pyruvate kinase enzyme levels
Usually necessary to test affected child and their parents to confirm the diagnosis
What happens in autoimmune haemolytic anaemia (AIHA)?
An antibody against a persons own red cells is produced
What can AIHA be divided into?
Warm and cold types
What is the difference between warm and cold AIHA?
In warm, antibody binds most strongly at 37 degrees
In cold, binds most strongly at 4 degrees
What antibody is usually involved in warm AIHA?
IgG
What antibody is usually involved in cold AIHA?
IgM
When does AIHA most commonly present in children?
During intercurrent infection
What normally happens when AIHA occurs during intercurrent infection?
It resolves spontaneously
What might AIHA occur in association with?
- Another immunological disorder, such as SLE or juvenile idiopathic arthritis (JIA)
- Lymphoproliferative disorder, such as Hodgkin’s lymphoma
How is a diagnosis of AIHA confirmed?
- Characteristic blood film
- Haemolysis profile
- Positive DAT
What is a haemolysis profile?
- Unconjugated hyperbilirubinaemia
- Raised LDH
- Increased reticulocytes
- Reduced haptoglobin levels
What might be required in causes of AIHA that do not resolve spontaneously?
Immunosuppressive treatment, such as steroids, azathioprine, or cyclosporin
