thalassaemias

thalassaemias

beta-thal
1. most often occur in people from
  1. Indian subcontinent
  2. Mediterranean
  3. Middle East
2. 2 types- both have severe reductn in prodn beta-globin (& so drop in HbA prodn)
  1. disease severity depends on amount of residual HbA & HbF prodn
    1. beta-thal major
      1. MOST SEVERE FORM
      2. can't make HbA (alpha2 beta 2) cos of abnormal beta-globin gene
      3. clinical features
        pallor
        jaundice
        bossing of skull & maxillary overgrowth
        hepatosplenomegaly
        need for repeated blood transfusions
    2. beta-thal intermedia
      1. milder form & variable severity
      2. beta-globin mutations allow small amount of HbA &/or large amount of HbF to be made
3. clinical features
  1. severe anaemia
    1. transfusion-dependent
    2. from age 3-6 months old
    3. + jaundice
  2. failure to thrive/growth failure
  3. extramedullary haemopoiesis
    1. prevent by regular blood transfusions
      1. if not prevented ->
        hepatosplenomegaly
        bone marrow expansion
        -> classical facies
        maxillary overgrowth & skull bossing
        rare in developed countries
4. Mx
  1. lifelong monthly RBC transfusions
    1. beta thal fatal w/o these
    2. aim= keep [Hb] > 10g/dl
      1. to reduce growth failure
      2. to prevent bone deformation
    3. cause chronic Fe overload (cos repeated)
      1. ->cardiac failure
      2. ->liver cirrhosis
      3. ->diabetes
      4. ->infertility
      5. ->growth failure
      6. so Rx w/ ... from 2-3 years old
        iron chelation e.g. subcut desferrioxamine
        oral iron chelator drug e.g. deferasirox
        compliance hard but good comp w/ both -> 90% chance of living til 40s
        if can't comply, high mortality in early adulthood from overload
    4. complications of multiple transfusions
      1. iron deposition
        the most imp complication
        seen in all pts
        heart-cardiomyopathy
        liver-cirrhosis
        pancreas- diabetes
        pituitary gland- delayed growth & sexual maturation
        skin-hyperpigmentation
      2. antibody formation (10% of kids)
        allo-antibodies to transfused RBCs in pts make finding compatible blood hard
      3. infection (now uncommon <10% of kids)
        hepatitis A, B, C
        HIV
        malaria
        prions e.g. new variant CJD
      4. venous access
        common prob
        often traumatic in young kids
        may need central venous access device e.g. portacath
        predispose to infection
  2. bone marrow transplantation
    1. the only cure
    2. only for kids w/ an HLA-identical sibling
      1. cos then 90-95% chance of transfusion independence & long-term cure (success) but 5% chance of transplant-related mortality
5. prenatal diag
  1. for parents both heterozyg for beta-thal
    1. means 1 in 4 risk of having an affected child
  2. offer DNA analysis of chorionic villus sample + genetic counselling
    1. help parents make informed decision re to continue preg
beta-thal trait
1. heterozygotes usually asymptomatic
2. hypochromic & microcytic RBCs
  1. so can be confused w/ mild iron def
    1. tell apart by measuring serum ferritin
      1. low in iron def NOT beta thal trait
        measure serum ferritin in pts w/ mild anaemia & microcytosis before starting iron supplements
        avoid unnecessary Fe therapy
3. mild or absent anaemia
  1. + disprop drop in MCH (18-22 fl) & MCV (60-70 fl)
    1. so RBC count usually raised (> 5.5 x 10^12/L)
4. raised HbA2= most imp diag feature
  1. usually seen in about 5%
5. mild elevatn of HbF by 1-3% in 50%
alpha-thal
1. manifestation depends on no of functional alpha-globin genes
  1. alpha-thal major
    1. aka Hb Barts hydrops fetalis
    2. cause= deletion of all 4 alpha globin genes
      1. so no HbA (alpha2 beta2) can be made
    3. occurs in families of S. East Asian origin
    4. presents mid-trimester
      1. fetal hydrops (oedema & ascites)
        from fetal anaemia
        always fatal in utero or within hours of delivery
        long-term survivors are those who got monthly intrauterine transfusion til delivery + lifelong monthly transfusions after birth
    5. diag
      1. Hb electrophoresis
      2. Hb HPLC (high performance liquid chromatography)
        only shows Hb Barts
  2. HbH disease
    1. 3 of alpha-globin genes deleted
    2. px often = mild-moderate anaemia
    3. some pts transfusion-dependent
  3. healthy ppl have 4 func alpha-globin genes
  4. alpha-thal trait
    1. = deletion of 1 or 2 alpha-globin genes
    2. asymptomatic
    3. mild/absent anaemia
    4. hypochromic & microcytic RBCs
      1. so can be confused w/ iron def

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