Thalassemia is a group of hemoglobinopathies leading to chronic anemia due to ineffective erythropoiesis, predominantly affecting ATP levels in red blood cells. Mitapivat, an allosteric activator of pyruvate kinase, improves ATP production in RBCs, which is crucial for managing anemia. Common genetic mutations, particularly deletions in the α-globin gene, play a significant role in the severity of α-thalassemia.

1. MIRZA NUMAN
IMPACT OF MITAPIVAT FOR ALPHA THALASSEMIA
AND ROLE OF PREVALENT GENETIC MUTATIONS

2. Thalassemia
 The thalassemia comprise a group of hemoglobinopathies characterized
by ineffective erythropoiesis and hemolysis, which lead to chronic anemia
and associated complications.
 Thalassemic red blood cells (RBCs) do not have sufficient levels of
adenosine triphosphate (ATP) to meet their increased energy demands.
 Alpha-Thalassemia
 Beta- Thalassemia

3. Epidemiology
 Alpha-thalassemia has become a relatively
common clinical problem in North America,
North Europe, and Australia.

4. Etiology
 When there are not enough healthy red blood cells, there is also
not enough oxygen delivered to all the other cells of the body,
which may cause a person to feel tired, weak or short of breath.
This is a condition called anemia.
 People with thalassemia may have mild or severe anemia.
Severe anemia can damage organs and lead to death.

5. Mitapivat
 Mitapivat is an allosteric activator of pyruvate
kinase (PK), a key enzyme that regulates the
final step of glycolysis responsible for ATP
production in RBCs.

6. Mechanism:

8. Genetic Mutations
 The most common genetic defect in α-thalassemia is a
deletion in the α-globin gene involving one or both globin
genes such as -α3.7, -α4.2, --SEA, --THAI, -αCD59, -α20.5, -αIVS I-1
 A highly severe form of deletional α-thalassemia, known as
Haemoglobin (Hb) Bart’s hydrops fetalis, is a homozygous
α0-thalassemia deletion with a complete loss of functional
α-globin that leads to foetal death or death shortly after
birth

9. Graphical Representation

10. Any Question??????????????????