Thalassemia

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Thalassemia

  1. 1. What hematologists should know about thalassemia• Correct diagnosis• Counselling• Complications and prevention• Plan of management
  2. 2. Hb electrophoresisA2 E A H<10% = A2 F Bart’s>10% = E
  3. 3. Thalassemia• globin• Alpha thalassemia – alpha globin – globin , beta globin• Beta thalassemia – beta globin – delta, gamma globin – Alpha
  4. 4. • Hb E A2 report – Peak 10% A2 – Peak 10% E•E F Hb beta chain• Bart H Hb alpha chain
  5. 5. alpha thalassemia• Hb typing rule out Hb H disease• Bart H CS Hb H disease• Alpha thal 1 trait MCV• Alpha thal 2 trait family history• DNA analysis rule in, rule out 100%
  6. 6. MCV IB Hb H Bart’s Bart’s in cord blood thal 2 trait Low Neg - - 1-2 %- / normal thal 1 trait 60-70 1:10,000 - - - 10%--/ 1:50,000Hb H disease 55-70 20-50% 0-20% 0-10% 20-30%--/- CS--/ + CS 3-5%
  7. 7. Hb Constant Spring (CS)1 Normal Normal globin Stop codon mutated1 CS (unstable)
  8. 8. Hb CS• Genotype CS (never CS CS or - CS)• Phenotype : resemble thal 2 (- )• Typing – CS trait: CS 1% – CS homozygous: CS 5% – CS/ thal1 : clinical = Hb H, CS 3-5%
  9. 9. Globin synthesis in thalassemiaNormal thal trait thal major
  10. 10. beta thalassemia• Beta trait A2 < 3 = normal > 4 = Beta trait• Beta major F A2
  11. 11. Abnormal splicing Beta globin gene with mutation = beta E Exon 1 Intron 1 Exon 2Exon 1 Exon 2 Normal splicingbeta E Exon 1 Exon 2 Abnormal splicing Abnormal globin, will be degraded in cytoplasm
  12. 12. Globin synthesis in Hb EHb E trait Hb E homozygous
  13. 13. Globin synthesis in thal/Hb E
  14. 14. Hb E• E 80% F E/ E• E 60-80% F 0/ E• E 40-60% FA +/ E• E 25-40% A / E• E 15-25% A / E alpha thal trait
  15. 15. Typing in beta thalassemia genotype MCV A2 F+alkF E A trait / 0 low > 3.5 <3%E trait / E low with E 1% 25-30% 70-75% normal thal 0/ 0, low 2-10% >90% - 0 +/ + 0/ + 0/ E, low with E 20-25% 60-70%thal/HbE +/ E 10-50% 40+% 10-50%HbE E/ E low with E 0-20% >80% 0homo normal
  16. 16. Alpha and beta thalassemia• Alpha thal beta major• Hb H E homozygous = EF Bart• Hb H E trait = AE Bart
  17. 17. alpha thalassemia with Hb E genotype MCV IB E F Bart’s thal1 trait/ --/ Low + 14-22% - -E trait / E thal2 trait/ - / Normal Neg 25-30% - -E trait / EHb H/ --/- 60-69 + 13-16% - 2-8%E trait / EHbH/ --/- Low Neg 80% 10% 3-4%E homo / E
  18. 18. Father Mother Child 1 Child 2Hb/Hct 14.2/40 11/32.9 10.4/30.1 9.8/27.4Retic 0.3 0.2 0.2 1.7IB - - - -Hb typing A 75.5 69.0 71 - E 24.5 31.0 28.6 100 Alk F 0.26 1.2 1.1 2.8
  19. 19. Father Mother Child 1Hb/Hct 11.8/38 13.5/39.2 9.9/32.6Retic 0.5 1.1 0.6IB 1:10,000 - >50%MCV 52 82 66Hb typing A 85.8 96.8 95.0 A2 3.2 1.6 E 14.2 Alk F 1.5 1.0 5.5
  20. 20. Father Mother Child 1 Child 2Hb/Hct 16.2/51 11.4/31.4 8.7/27.7 6.4/23Retic 1.0 1.0 5% 6.4IB rare > 1:20,000 1:5,000 > 50%MCV 81 61 62 67Hb typing A 73.2 95.9 70.1 67.0 A2 3.1 2.7 F - - - - E 26.8 14.4 H - - - 11.6 Bart’s - - 15.5 16.7 Alk F 1.6 1.7 7.4 5.6
  21. 21. Father Mother Child 1Hb/Hct 14.3/41.5 12.5/35.5 8.1/24.5Retic 0.7 0.2 5.5IB - - -MCV 62 83 49Hb typing A 92.7 65.9 - A2 7.29 F - - 27.2 E 34.0 72.7 Alk F 1.89 1.81 20.95
  22. 22. Father Mother Child 1Hb/Hct 14.5/42.5 13.6/39.6 10.6/31.9Retic 1.2 3.6 7.9IB - - 1:20,000MCV 79 81 77Hb typingA 96.9 94.2 95.4A2 3.1 2.5 2.3CS 3.3 2.3Alk F 0.3 1.0 1.9
  23. 23. Father Mother Child 1 Child 2Hb/Hct 13.5/40 12.0/35 8.7/25 13/41Retic 1.2 2.2 5.6 1.5IB - - - -MCV 72.4 77.8 67.4 85Hb typingA 96.0 77.0 25.0 98.5A2 4.0 1.5F 20.0E 23.0 55.0
  24. 24. Types of transfusion program• Hypertransfusion program – normalize growth and endocrine function – pre transfusion Hb level 9.5-10 mg/dl• Symptomatic transfusion
  25. 25. Blood products for transfusion• Leucodepleted red cells – less than 5 x 106 WBC/cumm – pre storage or post storage filtration – decrease alloimmunization• Washed red cells• Blood products should be used within 2 weeks after colllection
  26. 26. Adverse reaction of transfusion• Febrile non-hemolytic transfusion reaction• Allergic reaction• Acute hemolytic reaction• Delayed hemolytic transfusion reaction• TaGVH• Transfusion transmitted diseases
  27. 27. Allo-immunization• 3%• antibody Rh, Duffy, Kell, Kidd blood group• leucodepleted blood products
  28. 28. Autoimmune hemolytic anemia•• thalassemia• – Steroid – IVIG – Splenectomy
  29. 29. Post transfusion hypertension• 30% cerebral hemorrhage• 3-7 units• 1-15
  30. 30. Iron overload• Source of Fe – Blood products (5-10 gm/ year) – Fe in food (1-2 gm/ year)• Defined by total body iron of more than 20 gm.• Gold standard in diagnosis : liver biopsy• Serum ferritin may be useful as non-invasive test.• MRI: T2*
  31. 31. Complications from Fe overload• Endocrine dysfunction – hypothyroidism – DM – adrenal gland dysfunction• Cardiovascular problems• Liver fibrosis
  32. 32. Iron chelation• Desferrioxamine (Desferol ®) – subcutaneous infusion – infusion pump (20,000+ ) – 500-1500 mg 3-7 – 200 / 500 mg• Oral Iron chelator – Deferiprone – Deferasirox
  33. 33. Comparison of iron chelators
  34. 34. Advantages of oral chelators• More compliance• More effective for cardiac iron deposition
  35. 35. Consideration before initiating chelation• Organ damage from Fe overload is not reversible. ???• Compliance is the most important factors for success.• Complete vision and auditory function should be done.
  36. 36. Desferrioxamine administrationInitiation• After 10-20 transfusions• Serum ferritin more than 1,000 microgram/LDose• 20-40 mg/kg subcut. infusion over 8-12 hours 6 times a week.
  37. 37. Thromboembolic problems• : Pulmonary thromboembolism• hypoxemia 20% hypoxemia 50%• Post splenectomy : increased thrombosis, increased platelet aggregrability• Daily ASA might be helpful.
  38. 38. Bone marrow transplantation• The only current technique to ‘cure’ thalassemia• donor HLA thalassemia – – Unrelated donor• : hepatomegaly portal fibrosis hemochromatosis ( )
  39. 39. Modulation of gene productivity• Increase gene activity will lessen anemic symptoms• Agents proved to increase gene activity – Hydroxyurea – Butyrates
  40. 40. Frontiers in thalassemia• Iron chelation• Epigenetics• Transplantation

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