Makindo Medical Notes

Related Subjects: |Sideroblastic Anaemia |Splenectomy |Paroxysmal Nocturnal Haemoglobinuria |Pernicious anaemia |Normocytic anaemiaa |Pyruvate Kinase deficiency |Blood Products - Platelets |Von Willebrand Disease

Pyruvate kinase (PK) deficiency results in reduced ATP production within red blood cells (RBCs). This deficiency leads to a high concentration of 2,3-DPG, which inhibits enzymes of the pentose phosphate pathway, ultimately causing premature haemolysis of RBCs.

About

• Pyruvate kinase deficiency is an inherited autosomal recessive condition affecting RBCs.
• Deficient ATP production leads to a shortened red cell lifespan, resulting in chronic haemolytic anaemia.
• This condition is a form of congenital non-spherocytic haemolytic anaemia.

Epidemiology

• Pyruvate kinase deficiency follows an autosomal recessive inheritance pattern.
• Affected individuals are either homozygous or compound heterozygotes for mutations in the PKLR gene.

Aetiology

• Pyruvate kinase is an essential enzyme in the glycolytic pathway, responsible for catalyzing the conversion of phosphoenolpyruvate (PEP) to pyruvate, generating ATP in the process.
• In PK deficiency, mutations in the PKLR gene lead to reduced activity of the enzyme, resulting in insufficient ATP production in RBCs.
• Without adequate ATP, RBCs lose their flexibility, leading to increased fragility and premature removal by the spleen (extravascular haemolysis).
• Increased 2,3-DPG levels shift the oxygen dissociation curve to the right, facilitating oxygen release to tissues but also contributing to the instability of RBCs.

Clinical Features

• Highly variable. From severe neonatal jaundice and haemolysis to mild haemolysis detected in adulthood.
• Pallor, jaundice, fatigue, splenomegaly, and gallstones (due to chronic bilirubin production).
• Neonates may present with severe anaemia and require exchange transfusions.
• Aplastic crises, with Parvovirus B19, may lead to severe drops in haemoglobin levels.

Investigations

• Blood film shows "prickle cells" (spiculated red cells).
• Low haemoglobin (variable anaemia).
• Elevated reticulocyte count (reticulocytosis).
• Elevated lactate dehydrogenase (LDH) and bilirubin (markers of haemolysis).
• Low serum haptoglobin (due to haemolysis).
• Direct antiglobulin test (DAT/Coombs test) is negative.
• Definitive diagnosis is made by measuring low pyruvate kinase enzyme activity in RBCs.

Complications

• Chronic haemolysis increases the risk of developing gallstones (cholelithiasis).
• Aplastic crises can occur, particularly following infections like Parvovirus B19, leading to severe anaemia.
• Iron overload may result from repeated blood transfusions.

Management

• Management depends on the severity of the condition and symptoms:
  • Supportive care, including regular transfusions for severe anaemia, especially during aplastic crises.
  • Daily folic acid supplementation (5 mg/day) is recommended to support erythropoiesis.
  • Splenectomy may be considered for patients with severe haemolysis or high transfusion requirements, as it can reduce the rate of RBC destruction.
• During aplastic crises (e.g., viral infections), intensive supportive care with transfusions and careful monitoring is needed.
• Iron chelation therapy may be necessary for patients requiring frequent transfusions to prevent iron overload.