A Case of Thalassemia

1. Case of the weekCase of the week
Jagdish KJagdish K
Prof. A. Gowrishankar’s unitProf. A. Gowrishankar’s unit

2. 25yr old male presented to us for getting 25yr old male presented to us for getting
evaluated for anemia.evaluated for anemia.
He was apparently normal 10yrs ago, He was apparently normal 10yrs ago,
following which he developed fever for following which he developed fever for
two days.two days.
He went to a practitioner and diagnosed He went to a practitioner and diagnosed
to have low Hb and was transfused two to have low Hb and was transfused two
units of blood.units of blood.

3. Neither Hb value nor indication for Neither Hb value nor indication for
transfusion was known.transfusion was known.
Patient’s Hb is on the lower side for the Patient’s Hb is on the lower side for the
past 5yrs.past 5yrs.

4. No h/oNo h/o
Chest painChest pain
PalpitationPalpitation
Giddiness Giddiness
DizzinessDizziness
SyncopeSyncope
PresyncopePresyncope
Undue fatiguabilityUndue fatiguability
No h/oNo h/o
Abdominal painAbdominal pain
Nausea / vomitingNausea / vomiting
Altered bowel habitsAltered bowel habits
Hematemesis / melena / hematocheziaHematemesis / melena / hematochezia

5. No h/oNo h/o
DiplopiaDiplopia
DysphagiaDysphagia
DysarthriaDysarthria
Motor / sensory deficitsMotor / sensory deficits
Involuntary movementsInvoluntary movements
Altered sensoriumAltered sensorium
No h/oNo h/o
Bleeding tendanciesBleeding tendancies
Chronic blood lossChronic blood loss
Recurrent infectionsRecurrent infections

6. Not a k/c/o DM, HT, TB, Not a k/c/o DM, HT, TB,
Works as a software consultant.Works as a software consultant.

7. ExaminationExamination
Well oriented, conscious, afebrileWell oriented, conscious, afebrile
Vitals : normalVitals : normal
Pallor +vePallor +ve
No icterus / cyanosis/ clubbing/ No icterus / cyanosis/ clubbing/
lymphadenopathy/ pedal edemalymphadenopathy/ pedal edema
No evidence of facial dysmorphismNo evidence of facial dysmorphism
Head to toe examination unremarkableHead to toe examination unremarkable

8. CVS : S1S2 +, no added soundsCVS : S1S2 +, no added sounds
RS: NVBS +RS: NVBS +
P/A : P/A :
Liver palpable 3cm below the costal marginLiver palpable 3cm below the costal margin
Spleen palpable 4cm below the costal Spleen palpable 4cm below the costal
marginmargin
No free fluidNo free fluid
CNS : NormalCNS : Normal

9. Patient was followed up on op basis as Patient was followed up on op basis as
requested.requested.

10. ProblemsProblems
Anemia since childhoodAnemia since childhood
Hepatosplenomegaly Hepatosplenomegaly

11. InvestigationsInvestigations
CBC:CBC:
Hb: 8 gm/dlHb: 8 gm/dl
PCV: 24 %PCV: 24 %
MCV: 62MCV: 62
MCH: 25MCH: 25
MCHC: 28MCHC: 28
Platelet: 2 lacsPlatelet: 2 lacs
ESR: 10/15 ESR: 10/15
RDW: 15%RDW: 15%

12. Peripheral smear :Peripheral smear :
 microcytic hypochromic blood picture with microcytic hypochromic blood picture with
anisopoikilocytosisanisopoikilocytosis
Corrected reticulocyte count : 2.13Corrected reticulocyte count : 2.13
CXR : NormalCXR : Normal
ECG : sinus tachycardiaECG : sinus tachycardia

13. LFTLFT
Tot Bil : 1.5Tot Bil : 1.5
Dir Bil : 0.2Dir Bil : 0.2
SGOT: 20SGOT: 20
SGPT: 22SGPT: 22
ALP: 120ALP: 120
Tot Protein: 6.2Tot Protein: 6.2
Albumin : 3.8Albumin : 3.8

14. RFT: RFT:
Urea : 22Urea : 22
Creatinine: 0.6Creatinine: 0.6
RBS: 98RBS: 98
Electrolytes : normalElectrolytes : normal
Urine routine : normalUrine routine : normal
Stool for occult blood / ova, cyst : Stool for occult blood / ova, cyst :
negativenegative

15. ANA:ANA:
dsDNAdsDNA
DCTDCT
IDCTIDCT
TIBC : 365TIBC : 365
S. Ferritin : 500S. Ferritin : 500
LDH -130LDH -130
Negative

16. Serum ironSerum iron: Male 65–177 : Male 65–177 μμg/dL ;g/dL ;
Female 50–170 Female 50–170 μμg/dL g/dL
TIBC: 250–370 TIBC: 250–370 μμg/dL g/dL
Transferrin saturationTransferrin saturation: Male 20–50%; : Male 20–50%;
Female 15–50%Female 15–50%
Serum ferritin: Male 20-250 Serum ferritin: Male 20-250 μμg/L, Female g/L, Female
15-150 15-150 μμg/Lg/L
[6[6

17. Hb electrophoresis:Hb electrophoresis:
A : 9%A : 9%
A2: 6%A2: 6%
F : 85%F : 85%
S : 0S : 0
Reported as thalassemia minorReported as thalassemia minor
Bone marrow aspiration:Bone marrow aspiration:
Marked erythroid hyperplasiaMarked erythroid hyperplasia
Otherwise normalOtherwise normal

18. Hb A – Hb A – αα 2 2 ββ 2 2
Hb A 2 - Hb A 2 - αα 2 2 δδ 2 2
Hb F - - Hb F - - αα 2 2 γγ 2 2

19. THAL MAJOR THAL MINOR THAL INTERMEDIA
< 2 yrs; asymptomatic variable
Transfusion dependent asymptomtic variable
Hb 2-3 g at presentationRarely < 9 variable
Hb F > A2 > A Hb F < 5 % Same as major
Florid clinical
manifestations
asymptomatic variable

20. Diagnosis Diagnosis
Probably thalassemia intermediaProbably thalassemia intermedia

21. HemoglobinHemoglobin
Heme + GlobinHeme + Globin
Globin chain : Globin chain :
4 subunits4 subunits
α, α, ββ, , γγ, , δδ, , εε chains chains
Thalassemia is a condition in which one Thalassemia is a condition in which one
more of the globin chain is not more of the globin chain is not
synthesised.synthesised.

22. ThalassemiaThalassemia
Described by Described by CooleyCooley & & LeeLee in 1925 in 1925
Initially coined as thalassic anemia Initially coined as thalassic anemia
Later termed as thalassemia Later termed as thalassemia
Thalassic Thalassic  sea sea

23. ββ thalassemia thalassemia
αα  tetramer tetramer αα
44
α with α with γγ  HbF HbF
α with α with δδ  Hb A2 Hb A2
Protection of HbFProtection of HbF

24. αα chain cross linked chain cross linked

Homo tetramer
Precipitates in RBC
Destroyed in marrow
Not soluble
Destroyed in spleen
Ineffective erythropoiesisExtravascular hemolysis

25. αα thalassemia thalassemia
αα part of fetal Hb and adult Hb part of fetal Hb and adult Hb (affected in utero & (affected in utero &
continues even after patient is born)continues even after patient is born)
ββ
44
tetramers relatively soluble. So no ineffective tetramers relatively soluble. So no ineffective
erythropoiesis but only extravascular hemolysis erythropoiesis but only extravascular hemolysis
(HbH)(HbH)
γγ
4 4
in utero is in utero is Barts HbBarts Hb

26. Anemia & thalassemiaAnemia & thalassemia
Ineffective erythropoiesisIneffective erythropoiesis
Extrvascular hemolysisExtrvascular hemolysis
Decreased synthesis of globin Decreased synthesis of globin  decreased Hb decreased Hb

27. IntermediaIntermedia
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 clinicalDifference between them is strictly clinical
Needless to do genotypingNeedless to do genotyping
Same genotype can be there for all the Same genotype can be there for all the
three.three.
Variable presentation for the same Variable presentation for the same
genotypegenotype

29. Endless mutations listless Endless mutations listless
deletions…deletions…

30. PathophysiologyPathophysiology

32. Symptoms and signsSymptoms and signs
Anemia and hemolysisAnemia and hemolysis
Medullary expansionMedullary expansion
Coarse faciesCoarse facies
OsteoporosisOsteoporosis
OsteopeniaOsteopenia

33. Extramedullary hematopoiesisExtramedullary hematopoiesis
HepatomegalyHepatomegaly
SplenomegalySplenomegaly
Nerve compressionsNerve compressions
Features of iron overloadFeatures of iron overload

34. Complications Complications
Organ failureOrgan failure
MC cause of death : cardiac failureMC cause of death : cardiac failure
Severe anemia & sequelaeSevere anemia & sequelae
Growth retardation in childrenGrowth retardation in children
Tumour like nerve compressionTumour like nerve compression
Chronic hypoxia & high output stateChronic hypoxia & high output state

35. ComplicationsComplications
Hypercoagulable statesHypercoagulable states
Why?Why?
Pulmonary embolismPulmonary embolism
CVACVA
TIATIA
PHTPHT
Moya MoyaMoya Moya

36. RaceRace
AgeAge
SexSex

37. Lab diagnosisLab diagnosis
CBC CBC
Peripheral smearPeripheral smear
Hb electrophoresis: Hb electrophoresis:
normal -adultsnormal -adults
A :95-98%A :95-98%
A2: 2-3%A2: 2-3%
F: <2%F: <2%
S: 0S: 0
New born:New born:
HbF: 50-80%HbF: 50-80%
6months:6months:
HbF: 8%HbF: 8%
>6months>6months
HbF: 1-2%HbF: 1-2%

38. In thalassemia intermediaIn thalassemia intermedia
HbF: 20-100%HbF: 20-100%
HbA2 : upto 7%HbA2 : upto 7%
HbA: 0-80%HbA: 0-80%
Serum iron studiesSerum iron studies
Endocrine profile for iron overload complicationsEndocrine profile for iron overload complications

39. LFTLFT
MRIMRI
Liver Liver  good correlation with hepatic iron good correlation with hepatic iron
concentration, not with ferritinconcentration, not with ferritin
Cardiac: correlation poorCardiac: correlation poor

40. Genotyping: Genotyping:
usually not neededusually not needed
Done only for antenatal cases and terminationDone only for antenatal cases and termination

41. Superconducting Quantum Interference Device Superconducting Quantum Interference Device
((SQUIDSQUID))
Non invasiveNon invasive
CostlyCostly
Good relaibilityGood relaibility
Little inferior to biopsyLittle inferior to biopsy
Uses very low power magnetc fieldUses very low power magnetc field

42. Will a patient diagnosed as Will a patient diagnosed as
thalassemia intermedia progress thalassemia intermedia progress
to thalassemia major…?!?to thalassemia major…?!?

43. Medical careMedical care
Monitoring Monitoring
TransfusionTransfusion
To maintain Hb >7 ( leucocyte depleted)To maintain Hb >7 ( leucocyte depleted)
SplenectomySplenectomy
If no response to transfusionIf no response to transfusion
Profound pancytopeniaProfound pancytopenia

44. Chelation Chelation ( when to start?)( when to start?)
LIC 1.5mg/gm of liver tissueLIC 1.5mg/gm of liver tissue
Or simply ferritin > 1gmOr simply ferritin > 1gm

45. Chelating agentsChelating agents
Desferroxamine s/c infusion 8-12hrs 5/7Desferroxamine s/c infusion 8-12hrs 5/7
DeferiproneDeferiprone
Defarisirox : Defarisirox :
oral oral
OD doseOD dose
Highly efficientHighly efficient
Already hit the market and running successfullyAlready hit the market and running successfully

46. NutritionNutrition
Folic acidFolic acid
Vitamin CVitamin C
When to give? When not?When to give? When not?
Bone marrow transplant if progression to majorBone marrow transplant if progression to major
Yersinia enterocolitis is a common complication in Yersinia enterocolitis is a common complication in
iron overload. ( Septran for diarrhoea)iron overload. ( Septran for diarrhoea)

47. Take home messagesTake home messages
Difference between three types is strictly clinicalDifference between three types is strictly clinical
In Trait Hb rarely <9, totally asymptomaticIn Trait Hb rarely <9, totally asymptomatic
Major – first or second yr of life – transfusion Major – first or second yr of life – transfusion
dependentdependent
Intermedia ------ inbetweenIntermedia ------ inbetween

48. Take home messagesTake home messages
Diagnosed by Hb electrophoresisDiagnosed by Hb electrophoresis
Genotyping is unnecessary except for prenatal Genotyping is unnecessary except for prenatal
diagnosis. diagnosis.
Can have hypercoagulable statesCan have hypercoagulable states
Iron overload with or without transfusionIron overload with or without transfusion

49. Take home messagesTake home messages
SQUID – best noninvasive mode of assessing LICSQUID – best noninvasive mode of assessing LIC
Defarisirox– long acting, OD, highly effectiveDefarisirox– long acting, OD, highly effective
When in doubt treat as thalassemia majorWhen in doubt treat as thalassemia major

50. Thank you!!!Thank you!!!