hemoglobinopathy


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  • Hemoglobins

    • HgA = A2B2
    • HgF = A2Y2
    • HbA2 = A2D2
    • HbH = B4 = H-bodies
    • Fessas body = A4

  • Methods

    • Screening: Alkaline electrophoresis
    • Confirmatory: Acid electrophoresis
    • Quantification: HPLC

  • Workup indications

    • FHx
    • ethnicity (Medi, SE Asia, Africa)
    • unexplained anemia, cyanosis, polycythemia
    • antenatal screening

  • Normal

    • 98% A
    • 2% A2
    • 2nd trimester -> 1 year: 80% F
    • 1st trimester: Gower1 -> Portland -> Gower2

  • Alpha thalassemia

    • caused by deletions, microcytic hypochromic anemia, normal RDW
    • one gene deletion = AA/A- = silent
    • 2 gene deletion = trait = AA/-- or A-/A- = asymptomatic, mild anemia, nml electrophoresis
      • Hb Bart if at birth
      • HbCS (slow band) if constant spring
    • 3 gene deletion = A-/-- = hemolytic anemia, reticulocytosis, HbH
    • 4 gene deletion = A0 = incompatible with life, Hb Barts (Y4), minor HbH (B4), HbPortland

  • Beta thalassemia

    • caused by point mutations
    • minor: B0/B, asymptomatic
    • trait: B+/B, asymptomatic
    • intermedia: B+/B+, anemia, bone deformities, organomegaly, iron overload
    • major (Cooley): B0/B0, transfusion dependent, bone, organomegaly, iron overload

  • S

    • Glu -> Val (GAG->GTG)
    • trait: 40% S
    • anemia: 90% S

  • C

    • Glu -> Lys
    • trait: not anemic, has mild microcytosis, lots of targets, no xtals. C band is 35-40%
    • disease: mild-mod anemia, microcytosis, lots of targets, occ xtals. C band is dominant, A is absent. F is 0-3%.

  • Other hemoglobinopathies

    • D, E = asymptomatic
    • delta: defects in HbA2, can mask A2 elevation in beta thal trait
    • gamma: decreased YG:YA ratio at birth
    • delta-beta: mild except for epsi-Y-delta-beta thal, infants are transfusion dependent
    • hereditary persistance of HbF: asymptomatic, normal cbc and smear
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