This presentation is an overview of Hemolytic anemia with respect to enzyme deficiencies. The inheritance pattern, clinical manifestations, symptoms complications, diagnosis and management of different types of enzyme deficiencies such as G6PD and Pyruvate Kinase have been discussed in detail.

1. HEMOLYTIC ANEMIA:
G6PD Deficiency and Pyruvate Kinase Deficiency
Presentation By:
Dr. Almas Arshad

2. Learning Objectives
• Introduction of Hemolytic Anemia
• Enzyme deficiency and Hemolytic Anemia.
• G6PD Deficiency.
• Pyruvate Kinase.
• Diagnosis.
• Management of the conditions.

3. Introduction:
• Hemolytic anemia is characterized by the premature destruction of
red blood cells (hemolysis) at a faster rate than their production.
• Two common causes of hemolytic anemia are G6PD deficiency and
pyruvate kinase deficiency.

5. G6PD DEFICIENCY

6. G6PD:
• Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme.
• Protects the RBCs from oxidative stress.
• Essential component of HMP pathway (where reduced NADPH is
produced)
• NADPH is required for:
• Maintenance of Glutathione.
• Maintenance of Reduced Glutathione.
• Maintenance of Reduced form of protein sulfhydryl groups

7. Glucose-6-phosphate dehydrogenase (G6PD)
Deficiency:
Insufficient or defective G6PD enzyme deficiency.
One of the most common enzyme deficiencies.
Inherited X – Linked recessive disorder.
Primarily affect male than females.
Causes Hemolytic Anemia.

8. G6PD
Deficiency:
Reduced
NADPH
production.
Decreased
production of
reduced
glutathione
Increased
oxidative stress
(H2O2)
Decreased RBC
membrane
stability
Increased RBC
lysis (Increased
Hemolysis)
Hemolytic
Anemia
Oxidation of
sulfhydryl groups
of proteins.
Heinz bodies
accumulation.
Attach to RBC
wall.
Increased
Rigidity of wall.
Hemolytic Anemia

9. GDPD Deficiency:

10. G6PD Induced
Hemolytic Anemia:
• G6PD-deficient RBCs are susceptible to damage and destruction.
• Symptoms: Fatigue, jaundice, shortness of breath, rapid heart
rate, dark-colored urine, Neonatal jaundice (unconjugated
bilirubin)
• Reduces the lifespan.
• Precipitating factors:
• Oxidant Drugs (Antimalarials, Antibiotics, Antipyretics).
• Favism - Ingest fava beans.
• Severe infection (Inflammatory response  Oxidative
radicals  Oxidative damage  Hemolytic Anemia)

11. G6PD Variants:
CLASS CLINICAL SYMPTOMS RESIDUAL ENZYME ACTIVITY
I
Rare
Very severe (chronic hemolytic
anemia)
Occur even the absence of
precipitating factors.
<10%
II Severe (Episodic hemolytic
anemia)
<10%
III
Unstable G6PD enzyme
Moderate hemolytic anemia 10 – 60%
IV None > 60%

12. Diagnosis and Management
of G6PD Deficiency:
• Diagnosis:
• Blood tests: CBC, Reticulocyte count, G6PD enzyme assay
(Qualitative and quantitative).
• Genetic testing – for detection of G6PD gene mutation.
• Management:
• Avoiding triggers.
• Educating patients about potential triggers and the
importance of prevention.
• Monitoring for signs of hemolysis and seeking medical
attention when necessary.

13. PYRUVATE KINASE
DEFICIENCY

14. Pyruvate Kinase:
• Less common than
• Enzyme in Glycolysis
• Pyruvate Kinase Deficiency:
• Autosomal recessive.
• Mutation of PKLR gene.
• Symptoms: Anemia, jaundice,
Splenomegaly.
• Triggers: Infections, certain medications.

15. Mechanism:
• ATP Depletion (RBC prone to destruction)
• Accumulation of 2,3-BPG (Increases Osmotic fragility).
• Reduced NADPH production. (Oxidative stress).
• Rigid cell membrane (Na/K pump, H2O, cellular swelling)

16. Pyruvate
Kinase
deficiency
Decreased level
of ATP.
Decreased
activity of Na/K
pump.
Increased
intracellular Na
Causes water to
move into the
cell.
Osmotic fragility,
Swelling of RBC
Intravascular
Hemolysis
Loss of Biconcave
shape.
Chronic
extravascular
hemolysis

17. Diagnosis Pyruvate Kinase
Deficiency:
• Diagnosis:
• Blood test:
CBC, Reticulocyte count.
PK enzyme assay.
LDH
Unconjugated bilirubin
• Genetic testing to identify specific
mutations.

18. Management:
• Management:
• Avoidance of triggers.
• Iron and Folate supplementation to support RBC production.
• Blood transfusions in severe cases.
• Bone marrow transplant.
• Regular monitoring.

19. Other Enzyme Deficiencies:
• Hexokinase deficiency.
• Glutathione synthetase deficiency.

20. CONCLUSION
• Hemolytic anemia can be caused by enzyme deficiencies.
• The enzymes involved in Hemolytic Anemia include:
• G6PD.
• Pyruvate kinase.
• Hexokinase.
• Glutathione Synthetase.
• Timely diagnosis, management, and avoidance of triggers are essential for
individuals with these conditions.

21. References:
• Lippincott’s Illustrated Reviews in Biochemistry, 6th edition.
• Luzzatto L, Seneca E. G6PD deficiency: a classic example of pharmacogenetics
with on-going clinical implications. Br J Haematol. 2014;164(4):469-480. doi:
10.1111/bjh.12668.
• Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet.
2008;371(9606):64-74. doi: 10.1016/S0140-6736(08)60073-2.
• Beutler E. Glucose-6-phosphate dehydrogenase deficiency. N Engl J Med.
1991;324(3):169-174. doi: 10.1056/NEJM199101173240307.
• Zanella A, Bianchi P, Fermo E. Pyruvate kinase deficiency: the genotype-
phenotype association. Blood Rev. 2005;19(2):99-113. doi:
10.1016/j.blre.2004.08.001.
• Grace RF, Bianchi P, van Beers EJ, et al. Clinical spectrum of pyruvate kinase
deficiency: data from the Pyruvate Kinase Deficiency Natural History Study. Blood.
2018;131(20):2183-2192. doi: 10.1182/blood-2017-12-820534.

22. Thank You