A Case of Thalassemia
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  • 1. Case of the week Jagdish K Prof. A. Gowrishankar’s unit
  • 2.
    • 25yr old male presented to us for getting evaluated for anemia.
    • He was apparently normal 10yrs ago, following which he developed fever for two days.
    • He went to a practitioner and diagnosed to have low Hb and was transfused two units of blood.
  • 3.
    • Neither Hb value nor indication for transfusion was known.
    • Patient’s Hb is on the lower side for the past 5yrs.
  • 4.
    • No h/o
      • Chest pain
      • Palpitation
      • Giddiness
      • Dizziness
      • Syncope
      • Presyncope
      • Undue fatiguability
    • No h/o
      • Abdominal pain
      • Nausea / vomiting
      • Altered bowel habits
      • Hematemesis / melena / hematochezia
  • 5.
    • No h/o
      • Diplopia
      • Dysphagia
      • Dysarthria
      • Motor / sensory deficits
      • Involuntary movements
      • Altered sensorium
    • No h/o
      • Bleeding tendancies
      • Chronic blood loss
      • Recurrent infections
  • 6.
    • Not a k/c/o DM, HT, TB,
    • Works as a software consultant.
  • 7. Examination
      • Well oriented, conscious, afebrile
      • Vitals : normal
      • Pallor +ve
      • No icterus / cyanosis/ clubbing/ lymphadenopathy/ pedal edema
      • No evidence of facial dysmorphism
      • Head to toe examination unremarkable
  • 8.
    • CVS : S1S2 +, no added sounds
    • RS: NVBS +
    • P/A :
      • Liver palpable 3cm below the costal margin
      • Spleen palpable 4cm below the costal margin
      • No free fluid
    • CNS : Normal
  • 9.
    • Patient was followed up on op basis as requested.
  • 10. Problems
    • Anemia since childhood
    • Hepatosplenomegaly
  • 11. Investigations
    • CBC:
      • Hb: 8 gm/dl
      • PCV: 24 %
      • MCV: 62
      • MCH: 25
      • MCHC: 28
      • Platelet: 2 lacs
      • ESR: 10/15
      • RDW: 15%
  • 12.
    • Peripheral smear :
      • microcytic hypochromic blood picture with anisopoikilocytosis
    • Corrected reticulocyte count : 2.13
    • CXR : Normal
    • ECG : sinus tachycardia
  • 13.
    • LFT
      • Tot Bil : 1.5
      • Dir Bil : 0.2
      • SGOT: 20
      • SGPT: 22
      • ALP: 120
      • Tot Protein: 6.2
      • Albumin : 3.8
  • 14.
    • RFT:
      • Urea : 22
      • Creatinine: 0.6
      • RBS: 98
      • Electrolytes : normal
    • Urine routine : normal
    • Stool for occult blood / ova, cyst : negative
  • 15.
    • ANA:
    • dsDNA
    • DCT
    • IDCT
    • TIBC : 365
    • S. Ferritin : 500
    • LDH -130
    Negative
  • 16.
    • Serum iron : Male 65–177 μ g/dL ;
    • Female 50–170 μ g/dL
    • TIBC: 250–370 μ g/dL
    • Transferrin saturation : Male 20–50%;
    • Female 15–50%
    • Serum ferritin: Male 20-250 μ g/L, Female 15-150 μ g/L [6
  • 17.
    • Hb electrophoresis:
      • A : 9%
      • A2: 6%
      • F : 85%
      • S : 0
      • Reported as thalassemia minor
    • Bone marrow aspiration:
      • Marked erythroid hyperplasia
      • Otherwise normal
  • 18.
    • Hb A – α 2 β 2
    • Hb A 2 - α 2 δ 2
    • Hb F - - α 2 γ 2
  • 19. THAL MAJOR THAL MINOR THAL INTERMEDIA < 2 yrs; asymptomatic variable Transfusion dependent asymptomtic variable Hb 2-3 g at presentation Rarely < 9 variable Hb F > A2 > A Hb F < 5 % Same as major Florid clinical manifestations asymptomatic variable
  • 20. Diagnosis
    • Probably thalassemia intermedia
  • 21. Hemoglobin
    • Heme + Globin
    • Globin chain :
      • 4 subunits
      • α, β , γ , δ , ε chains
    • Thalassemia is a condition in which one more of the globin chain is not synthesised.
  • 22. Thalassemia
    • Described by Cooley & Lee in 1925
    • Initially coined as thalassic anemia
    • Later termed as thalassemia
    • Thalassic  sea
  • 23. β thalassemia
    • α  tetramer α 4
    • α with γ  HbF
    • α with δ  Hb A2
    • Protection of HbF
  • 24.
    • α chain cross linked
    Homo tetramer Precipitates in RBC Destroyed in marrow Not soluble Destroyed in spleen Ineffective erythropoiesis Extravascular hemolysis
  • 25. α thalassemia
    • α part of fetal Hb and adult Hb (affected in utero & continues even after patient is born)
    • β 4 tetramers relatively soluble. So no ineffective erythropoiesis but only extravascular hemolysis (HbH)
    • γ 4 in utero is Barts Hb
  • 26. Anemia & thalassemia
    • Ineffective erythropoiesis
    • Extrvascular hemolysis
    • Decreased synthesis of globin  decreased Hb
  • 27.
    • Intermedia
    • Major ----- Homozygous β 0 / β 0
      • Minor ----- heterozygous
      • β 0 / n or β + /n
    • Beta thalessemia
      • Homozygous ---- β + / β +
      • Heterozygous ---- β + / β 0
      • Compound heterozygous --- β + / β 0 δ 0
  • 28.
    • Difference between them is strictly clinical
    • Needless to do genotyping
    • Same genotype can be there for all the three.
    • Variable presentation for the same genotype
  • 29.
    • Endless mutations listless deletions…
  • 30. Pathophysiology
  • 31.  
  • 32. Symptoms and signs
    • Anemia and hemolysis
    • Medullary expansion
      • Coarse facies
      • Osteoporosis
      • Osteopenia
  • 33.
    • Extramedullary hematopoiesis
      • Hepatomegaly
      • Splenomegaly
      • Nerve compressions
    • Features of iron overload
  • 34. Complications
    • Organ failure
      • MC cause of death : cardiac failure
    • Severe anemia & sequelae
    • Growth retardation in children
    • Tumour like nerve compression
    • Chronic hypoxia & high output state
  • 35. Complications
    • Hypercoagulable states
      • Why?
      • Pulmonary embolism
      • CVA
      • TIA
      • PHT
      • Moya Moya
  • 36.
    • Race
    • Age
    • Sex
  • 37. Lab diagnosis
    • CBC
    • Peripheral smear
    • Hb electrophoresis:
      • normal -adults
        • A :95-98%
        • A2: 2-3%
        • F: <2%
        • S: 0
    • New born:
      • HbF: 50-80%
    • 6months:
      • HbF: 8%
    • >6months
      • HbF: 1-2%
  • 38.
    • In thalassemia intermedia
      • HbF: 20-100%
      • HbA2 : upto 7%
      • HbA: 0-80%
    • Serum iron studies
    • Endocrine profile for iron overload complications
  • 39.
    • LFT
    • MRI
      • Liver  good correlation with hepatic iron concentration, not with ferritin
      • Cardiac: correlation poor
  • 40.
    • Genotyping:
      • usually not needed
      • Done only for antenatal cases and termination
  • 41. Superconducting Quantum Interference Device ( SQUID )
    • Non invasive
    • Costly
    • Good relaibility
    • Little inferior to biopsy
    • Uses very low power magnetc field
  • 42.
    • Will a patient diagnosed as thalassemia intermedia progress to thalassemia major…?!?
  • 43. Medical care
    • Monitoring
    • Transfusion
      • To maintain Hb >7 ( leucocyte depleted)
    • Splenectomy
      • If no response to transfusion
      • Profound pancytopenia
  • 44.
    • Chelation ( when to start?)
      • LIC 1.5mg/gm of liver tissue
      • Or simply ferritin > 1gm
  • 45. Chelating agents
    • Desferroxamine s/c infusion 8-12hrs 5/7
    • Deferiprone
    • Defarisirox :
      • oral
      • OD dose
      • Highly efficient
      • Already hit the market and running successfully
  • 46.
    • Nutrition
      • Folic acid
      • Vitamin C
        • When to give? When not?
    • Bone marrow transplant if progression to major
    • Yersinia enterocolitis is a common complication in iron overload. ( Septran for diarrhoea)
  • 47. Take home messages
    • Difference between three types is strictly clinical
    • In Trait Hb rarely <9, totally asymptomatic
    • Major – first or second yr of life – transfusion dependent
    • Intermedia ------ inbetween
  • 48. Take home messages
    • Diagnosed by Hb electrophoresis
    • Genotyping is unnecessary except for prenatal diagnosis.
    • Can have hypercoagulable states
    • Iron overload with or without transfusion
  • 49. Take home messages
    • SQUID – best noninvasive mode of assessing LIC
    • Defarisirox– long acting, OD, highly effective
    • When in doubt treat as thalassemia major
  • 50. Thank you!!!