Lecture 18 Alpha Thalassemias Flashcards
1
Q
Thalassemia
A
- genetically determined defect in hemoglobin synthesis
- inability to manufacture sufficient quantities of alpha or beta globin chains
2
Q
Alpha Thalassemias
A
- large deletions in alpha globin chains
- deletional mutations are predominant genetic defect
- non-deletional mutations (point mutations) are uncommon
- autosomal recessive
- 4 forms
3
Q
α°-thalassemia haplotype
A
- no alpha chains are produced
- (–)
4
Q
α+-thalassemia haplotype
A
- decreased alpha chain production due to deletional or nondeletional mutation
- designation is (-a)
5
Q
αтα
A
- denotes nondeletional mutation
- more unstable of fewer alpha globin chains than a- results in more severe anemia
6
Q
Constant Spring: (αcs )
A
- most common nondeletional alpha gene mutation
7
Q
Causes of Anemia in Alpha Thalassemia
A
- underproduction of HbA -> decreased Hgb production and ineffective eythropoiesis
- production of nonfunctional Hgbs b/c of insufficient alpha globin chains
- Hb Barts (excess gamma globin tetramers
- Hb H (excess beta globin tetramers)
- intramedullary and splenic hemolysis from globin chain imbalance
8
Q
Alpha Thalassemia Major
Hydrops Fetalis
A
- homozygous
- all 4 genes deleted
- no alpha chain produc’n
- HbA, HbA2, HbF absent from lack of alpha chains
- obstretical complications can lead to morbidity of mothers
- Hb Bart’s which consist of 4 gamma chains (tetramers of gamma chains) 80-90% at birth
10-20% of Hb Portland - little or no HbH**
- lethal (Hb Barts affinity for O2 10 times stronger)
9
Q
Hb Barts
A
- severe hypoxia with CHF
- liver and spleen often enlarged
- babies underweight
- PBS findings
- marked microcytosis and hypochromasia
- anisopoikilocytosis
- numerous nucleated RBCs
- marked anemia
10
Q
Hgb H disease (Alpha Thalassemia Intermedia)
A
- 3 genes abnormal
- 1 gene coding for alpha chains
- (–/-a) all children affected
- excess gamma chains at birth
- excess beta chains when production starts at 4-6 months of age
- both unstable and useless (both have strong affinity for O2)
- Hb Barts measured with Hgb electrophoresis
- Hb H detected one of 2 ways
- Hgb electrophoresis (quantitative)
- Hgb H inclusions (qualitative) -> golf ball stippled appearance
- Hb A main component (25-35% normal)
11
Q
HbH Lab Diagnosis
A
- retic count moderately elevated (5-10%)
- microcytosis/hypochromasia
- RBC histogram shift to left
- anisopoikilocytosis with target cells
- occ’l NRBCs
- basophilic stippling
- 10-40% of Hb Barts at birth
- 1-40% Hb H in adult
- Hb A is reduced
- Hb A2 is mildly reduced
- Hb F is normal
12
Q
HbH PBS
A
- low Hgb, microcytic, hypochromic
13
Q
HbH Treatment and Prognosis
A
- most pts require no treatment
- infections should promptly treated and avoid oxidant drugs (infectionas and oxidant drugs aggravate precipitation)
- pt life expectancy is normal
14
Q
Alpha Thalassemia Trait (minor)
A
- can be heterozygous (–/aa)
- can also be homozygous (-a/-a)
- most demonstrable abnormality is in newborn where Hb Barts is 5-15% -> disappears after 4-6 mos of life and is NOT replaced by HbH
- HbH inclusions may be visible
- DNA analysis may be required to confirm
15
Q
Alpha Thalassemia Trait
A
- Hgb and Hct may be at lower limit of normal range or mild anemia
- RBC count usually high normal to slight increase (important distinction from iron deficiency)
- MCV and MCH usually low, MCHC normal to slightly decreased
- RDW normal or only slightly increased
- target cells common
- no effect on life expectancy
- no clinical disease
