Hemolytic Anemia.pptx

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.

4. G6PD DEFICIENCY

5. 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

6. Glucose-6-phosphate dehydrogenase (G6PD) Deficiency:

7. GDPD Deficiency:

8. 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 ( A ntimalarials, A ntibiotics, A ntipyretics). Favism - Ingest fava beans. Severe infection (Inflammatory response  Oxidative radicals  Oxidative damage  Hemolytic Anemia)

9. 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%

10. 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.

11. PYRUVATE KINASE DEFICIENCY

12. 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.

13. 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)

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

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

16. Other Enzyme Deficiencies: Hexokinase deficiency. Glutathione synthetase deficiency.

17. 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.

18. 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.

19. Thank You