Case of the week Jagdish K Prof. A. Gowrishankar’s unit
<ul><li>25yr old male presented to us for getting evaluated for anemia. </li></ul><ul><li>He was apparently normal 10yrs a...
<ul><li>Neither  Hb value nor indication for transfusion was known. </li></ul><ul><li>Patient’s Hb is on the lower side fo...
<ul><li>No h/o </li></ul><ul><ul><li>Chest pain </li></ul></ul><ul><ul><li>Palpitation </li></ul></ul><ul><ul><li>Giddines...
<ul><li>No h/o </li></ul><ul><ul><li>Diplopia </li></ul></ul><ul><ul><li>Dysphagia </li></ul></ul><ul><ul><li>Dysarthria <...
<ul><li>Not a k/c/o DM, HT, TB,  </li></ul><ul><li>Works as a software consultant. </li></ul>
Examination   <ul><ul><li>Well oriented, conscious, afebrile </li></ul></ul><ul><ul><li>Vitals : normal </li></ul></ul><ul...
<ul><li>CVS : S1S2 +, no added sounds </li></ul><ul><li>RS: NVBS + </li></ul><ul><li>P/A :  </li></ul><ul><ul><li>Liver pa...
<ul><li>Patient was followed up on op basis as requested. </li></ul>
Problems   <ul><li>Anemia since childhood </li></ul><ul><li>Hepatosplenomegaly  </li></ul>
Investigations   <ul><li>CBC: </li></ul><ul><ul><li>Hb: 8 gm/dl </li></ul></ul><ul><ul><li>PCV: 24 % </li></ul></ul><ul><u...
<ul><li>Peripheral smear : </li></ul><ul><ul><li>microcytic hypochromic blood picture with anisopoikilocytosis </li></ul><...
<ul><li>LFT </li></ul><ul><ul><li>Tot Bil : 1.5 </li></ul></ul><ul><ul><li>Dir Bil : 0.2 </li></ul></ul><ul><ul><li>SGOT: ...
<ul><li>RFT:  </li></ul><ul><ul><li>Urea : 22 </li></ul></ul><ul><ul><li>Creatinine: 0.6 </li></ul></ul><ul><ul><li>RBS: 9...
<ul><li>ANA: </li></ul><ul><li>dsDNA </li></ul><ul><li>DCT </li></ul><ul><li>IDCT </li></ul><ul><li>TIBC : 365 </li></ul><...
<ul><li>Serum iron : Male 65–177  μ g/dL ; </li></ul><ul><li>Female 50–170  μ g/dL  </li></ul><ul><li>TIBC: 250–370  μ g/d...
<ul><li>Hb electrophoresis: </li></ul><ul><ul><li>A : 9% </li></ul></ul><ul><ul><li>A2: 6% </li></ul></ul><ul><ul><li>F : ...
<ul><li>Hb A –  α  2  β  2 </li></ul><ul><li>Hb A 2 -  α  2  δ  2 </li></ul><ul><li>Hb F - -  α  2  γ  2 </li></ul>
THAL MAJOR  THAL MINOR  THAL INTERMEDIA < 2 yrs; asymptomatic variable Transfusion dependent asymptomtic variable Hb 2-3 g...
Diagnosis  <ul><li>Probably thalassemia intermedia </li></ul>
Hemoglobin   <ul><li>Heme + Globin </li></ul><ul><li>Globin chain :  </li></ul><ul><ul><li>4 subunits </li></ul></ul><ul><...
Thalassemia   <ul><li>Described by  Cooley  &  Lee  in 1925 </li></ul><ul><li>Initially coined as thalassic anemia  </li><...
β  thalassemia <ul><li>α     tetramer  α 4 </li></ul><ul><li>α with  γ     HbF </li></ul><ul><li>α with  δ     Hb A2 </...
<ul><li>α  chain cross linked </li></ul><ul><li>  </li></ul>Homo tetramer Precipitates in RBC Destroyed in marrow Not solu...
α  thalassemia <ul><li>α  part of fetal Hb and adult Hb  (affected in utero & continues even after patient is born) </li><...
Anemia & thalassemia <ul><li>Ineffective erythropoiesis </li></ul><ul><li>Extrvascular hemolysis </li></ul><ul><li>Decreas...
<ul><li>Intermedia   </li></ul><ul><li>Major  ----- Homozygous  β 0  /  β 0 </li></ul><ul><ul><li>Minor  ----- heterozygou...
<ul><li>Difference between them is strictly clinical </li></ul><ul><li>Needless to do genotyping </li></ul><ul><li>Same ge...
<ul><li>Endless mutations listless deletions… </li></ul>
Pathophysiology
 
Symptoms and signs <ul><li>Anemia and hemolysis </li></ul><ul><li>Medullary expansion </li></ul><ul><ul><li>Coarse facies ...
<ul><li>Extramedullary hematopoiesis </li></ul><ul><ul><li>Hepatomegaly </li></ul></ul><ul><ul><li>Splenomegaly </li></ul>...
Complications  <ul><li>Organ failure </li></ul><ul><ul><li>MC cause of death : cardiac failure </li></ul></ul><ul><li>Seve...
Complications <ul><li>Hypercoagulable states </li></ul><ul><ul><li>Why? </li></ul></ul><ul><ul><li>Pulmonary embolism </li...
<ul><li>Race </li></ul><ul><li>Age </li></ul><ul><li>Sex </li></ul>
Lab diagnosis <ul><li>CBC  </li></ul><ul><li>Peripheral smear </li></ul><ul><li>Hb electrophoresis:  </li></ul><ul><ul><li...
<ul><li>In thalassemia intermedia </li></ul><ul><ul><li>HbF: 20-100% </li></ul></ul><ul><ul><li>HbA2 : upto 7% </li></ul><...
<ul><li>LFT </li></ul><ul><li>MRI </li></ul><ul><ul><li>Liver    good correlation with hepatic iron concentration, not wi...
<ul><li>Genotyping:  </li></ul><ul><ul><li>usually not needed </li></ul></ul><ul><ul><li>Done only for antenatal cases and...
Superconducting Quantum Interference Device ( SQUID ) <ul><li>Non invasive </li></ul><ul><li>Costly </li></ul><ul><li>Good...
<ul><li>Will a patient diagnosed as thalassemia intermedia progress to thalassemia major…?!? </li></ul>
Medical care <ul><li>Monitoring  </li></ul><ul><li>Transfusion </li></ul><ul><ul><li>To maintain Hb >7 ( leucocyte deplete...
<ul><li>Chelation  ( when to start?) </li></ul><ul><ul><li>LIC 1.5mg/gm of liver tissue </li></ul></ul><ul><ul><li>Or simp...
Chelating agents <ul><li>Desferroxamine s/c infusion 8-12hrs 5/7 </li></ul><ul><li>Deferiprone </li></ul><ul><li>Defarisir...
<ul><li>Nutrition </li></ul><ul><ul><li>Folic acid </li></ul></ul><ul><ul><li>Vitamin C </li></ul></ul><ul><ul><ul><li>Whe...
Take home messages <ul><li>Difference between three types is strictly clinical </li></ul><ul><li>In Trait Hb rarely <9, to...
Take home messages <ul><li>Diagnosed by Hb electrophoresis </li></ul><ul><li>Genotyping is unnecessary except for prenatal...
Take home messages <ul><li>SQUID – best noninvasive mode of assessing LIC </li></ul><ul><li>Defarisirox– long acting, OD, ...
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A Case of Thalassemia

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A Case of Thalassemia

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