Hemolytic Anemias: hemoglobinopathies and Thalassemias
Terms
-
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
- 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