Case of the week Jagdish K Prof. A. Gowrishankar’s unit
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.
Neither Hb value nor indication for transfusion was known.
Patient’s Hb is on the lower side for the past 5yrs.
Hematemesis / melena / hematochezia
Works as a software consultant.
Examination Well oriented, conscious, afebrile No icterus / cyanosis/ clubbing/ lymphadenopathy/ pedal edema No evidence of facial dysmorphism
Head to toe examination unremarkable
CVS : S1S2 +, no added sounds Liver palpable 3cm below the costal margin
Spleen palpable 4cm below the costal margin
Patient was followed up on op basis as requested.
microcytic hypochromic blood picture with anisopoikilocytosis
Corrected reticulocyte count : 2.13
Stool for occult blood / ova, cyst : negative
Serum iron : Male 65–177 μ g/dL ; Transferrin saturation : Male 20–50%;
Serum ferritin: Male 20-250 μ g/L, Female 15-150 μ g/L [6
Reported as thalassemia minor
Marked erythroid hyperplasia
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
Probably thalassemia intermedia
Thalassemia is a condition in which one more of the globin chain is not synthesised.
Thalassemia Described by Cooley & Lee in 1925 Initially coined as thalassic anemia
Later termed as thalassemia
Homo tetramer Precipitates in RBC Destroyed in marrow Not soluble Destroyed in spleen Ineffective erythropoiesis Extravascular hemolysis
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)
Anemia & thalassemia Ineffective erythropoiesis
Decreased synthesis of globin decreased Hb
Major ----- Homozygous β 0 / β 0 Homozygous ---- β + / β + Heterozygous ---- β + / β 0
Compound heterozygous --- β + / β 0 δ 0
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
Endless mutations listless deletions…
Symptoms and signs
Features of iron overload
Complications MC cause of death : cardiac failure Growth retardation in children Tumour like nerve compression
Chronic hypoxia & high output state
In thalassemia intermedia
Endocrine profile for iron overload complications
Liver good correlation with hepatic iron concentration, not with ferritin
Cardiac: correlation poor
Done only for antenatal cases and termination
Superconducting Quantum Interference Device ( SQUID ) Little inferior to biopsy
Uses very low power magnetc field
Will a patient diagnosed as thalassemia intermedia progress to thalassemia major…?!?
Medical care To maintain Hb >7 ( leucocyte depleted)
If no response to transfusion
Chelation ( when to start?)
LIC 1.5mg/gm of liver tissue
Chelating agents Desferroxamine s/c infusion 8-12hrs 5/7
Already hit the market and running successfully
Bone marrow transplant if progression to major
Yersinia enterocolitis is a common complication in iron overload. ( Septran for diarrhoea)
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
Take home messages Diagnosed by Hb electrophoresis Genotyping is unnecessary except for prenatal diagnosis. Can have hypercoagulable states
Iron overload with or without transfusion
Take home messages SQUID – best noninvasive mode of assessing LIC Defarisirox– long acting, OD, highly effective
When in doubt treat as thalassemia major