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Hemolytic Anemias: hemoglobinopathies and Thalassemias

Terms

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Classification of Hgb Disorders
  • Qualitative
    • Abnormal amino acid sequencing in globin chain
      • substitutions: 1,2 a.a.
      • deletion, addition, fusion
    • Hgb S,C,D,E
  • Quantitative
    • decreased sythesis of normal Hgb chain
Hemoglobin S: Pathophysiology
  • Single a.a. substitution in the 6th position of the beta chain from valine to gulatmic acid
  • Sickle cell anemia
    • homozygous for Hgb S (SS)
  • Sickle cell trait
    • heterozygous for Hgb S (SA)
Hemoglobin S: Sickling Hemoglobins Lab tests
  • Sickle cell prep = slide sickle prep test
    • sodium hydrosulfite (metabisulfite)
    • reduces O2 tension
  • Sickledex- solubility test for Hgb S
    • sodium dithionite
    • reduces O2 tension
  • Hemoglobin

Sickle Cell Anemia- Homozygous state

 

Clinical features 

  • affects 0.26% of African-Americans
  • Vascular occlusion (hemolysis)
    • spleen, liver, kidney, bone marrow
    • slow blood flow in sinuses
  • Generalized abnormal growth
  • bone and joint abnormalities
  • hepat

Sickle Cell Anemia- Homozygous state

 

Lab findings 

  • Hgb: 6-8 g/dL
  • Hct: 18-24%
  • RBC: 2-2.5X10^6/ul
  • RBC indices: normocytic, normochromic
  • increased reticulocyte count: 5-20%
  • peripheral blood smear
    • sickle cells, target cells,HJ bodies, NRBC, polychrom

Sickle Cell Anemia- Homozygous state

 

Treatment 

  • Manage crisis
    • pain medication
    • antibotic therapy
    • administer fluids
  • Bone marrow transplantation possibly a future treatment
  • Gene therapy??
  • Prognosis with treatment
    • 85% of SS patien

Sickle Cell Trait-  Heterozygous state

 

Clinical features 

  • affects 8-10% of African-Americans
  • usually asymptomatic
  • may have some sickling in kidney in crisis
  • crises occur respiratory infections, air travel or deep-sea diving in unpressurized situations, anesthesia, congestive heart

Sickle Cell Trait-  Heterozygous state

 

Lab findings 

  • usually don't present with hemolytic anemai except in crisis
  • peripheral blood smear doesn't normally have sickled cells except after crisis
  • Hgb electrophoresis:
    • 60% Hgb A, 40% Hgb S, and elevated Hgb A2 (3.6%)

Sickle Cell Trait-  Heterozygous state

 

Treatment 

  • Prevent high-risk situations
  • not necessary except in crisis
  • Prognosis
    • genetic counseling is key

Hgb C

 

Pathophysiology 

  • Single substitution in 6th position of B chain from lysine to gluatmic acid

Hgb C Disease

 

Clinical Features 

  • Affects 0.02% of Africans
  • mild chronic hemoltyic anemia with splenomegaly

Hgb C Disease

 

Lab findings 

  • RBC indices: normocytic, normochromic
  • slightly increased reticulocyte count
  • peripheral blood smear
    • 50-90% traget cells
    • few fragmented cells and microspherocytes
    • hgb C cyrstals following splenectomy (hgb

Hgb C Disease

 

Treatment and Prognosis 

  • usually not necessary
  • prognosis: good
Hgb C Trait
  • affects 2-3% of Africans
  • Clinically asymptomatic
  • may show some targeting on peripheral blood smear
  • Hgb electrophoresis
    • 60% Hgb A
    • 4% Hgb C
Hgb SC Disease
  • RBCs have both Hgb S and C
  • is milder disease than Hgb SS
  • may cause more severe retinal damage and femoral head damage due to increased blood viscosity
  • peripheral blood smear:
    • target cells, few intracellular Hgb
Hgb D Disease and Trait
  • pathophysiology: a.a. substitution of glutamine for gluatmic acid on the 121st position of the beta chain
  • both Hgb DD and DA are asymptomatic
  • few target cells present on peripheral blood smear
Hgb E Disease and Trait
  • More prevalent in US since migration of S.E. Asian refugees after vietnam war
  • may be protective against malaria
  • pathophysiology:
    • a.a. sub of lysine for gluatmic acid on the 26th position of beta chain
  • littl

Thalassemia

 

Pathophysiology 

  • decreased rate of production of normal globin chains
  • results in ppt of excess globin chains and increased destruction of RBCs
  • beta thalassemia has a deficiency in beta chains (has a, not as severe as alpha thalassemia)
  • Alph

Beta Thalassemia Major (Homozygous State)

 

Clinical features 

  • englarged spleen and liver
  • widening of skull and facial bones
  • growth and mental retardation
  • fractures
  • tumors in bone marrow
  • infections
  • iron overload

Beta Thalassemia Major (Homozygous State)

 

Lab findings 

  • severe microcytic, hypochromic anemia
  • Hgb less than 7 g/dL
  • increased reticulocytes up to 30%
  • increased serum iron
  • peripheral blood smear
    • NRBC, A&, thrombocytosis
  • Hgb Electrophoresis

Beta Thalassemia Major (Homozygous State)

 

Treatment 

  • regular blood transfusions
  • iron chelation therapy (doesn't overload in liver/spleen)
  • splenectomy
  • bone marrow transplants
  • prognosis: variable

Beta Thalassemia Minor (Heterozygous state)

 

Clinical features, treatment, prognosis

  • asymptomatic
  • no treatment usually needed
  • good prognosis

Beta Thalassemia Minor (Heterozygous state)

 

Lab findings 

  • mild form of chroni, microcytic, hypochromic anemia
  • Hgb levels from 10.5-13.9 g/dL
  • Hgb electrophoresis:
    • mostly Hgb A, slight increases in Hgb F and Hgb A2

Alpha Thalassemia Major

 

Hydrops fetalis syndrome

  • Hydrops fetalis syndrome
    • no alpha chains produced, only zeta and epsilon chains (embryonic chains)
    • 4 defective alpha genes
    • fetal RBCs contains Bart's Hgb, which has 4 gamma chains
    • Bart's hgb has a high

Alpha Thalassemia Major

 

Hemoglobin H disease 

  • 3 defectie alpha genes
  • hgb with 4 beta chains
  • decreased hgb and hct
  • hypochromia, target cells, some A&P
  • normal to slightly increased reticulocytes
  • Heinz bodies and Hgb H ppt with supravital stains
Alpha Thalassemia Minor
  • Asymptomatic
  • mild microcytic, hypochromic anemia
  • hgb usually 9-11 g/dL
  • usually requires no treatment
Hereditary Persistance of Fetal Hemoglobin
  • most prevalent in african
  • Homozygous state: 100% Hgb F
  • Heterozygous state: 15-30% Hgb F

Deck Info

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