10) Hemoglobinopathies & thalassemias Flashcards
hemoglobinopathy
defect in structure of globin chain
thalassemia
decreased rate of globin chain synthesis
2 alpha 2 beta
Hgb A
2 alpha 2 delta
Hgb A2
2 alpha 2 gamma
Hgb F
2 zeta 2 epsilon
Gower 1
2 alpha 2 epsilon
Gower 2
2 zeta 2 gamma
Portland
𝛼2β2 6 val
Hgb S
valine replaces glutamic acid on Beta
conditions under which sickling may occur in sickle trait
anesthesia
strenuous exercise
when does Hgb S sickle?
physiological oxygen tensions
deoyxgenation makes cell susceptible to sickling
3 factors sickling depends on
- degree of oxygenation
- pH
- dehydration
main cause of anemia in sickle cell anemia
extravascular hemolysis
spleen lyses fragile Hgb S cells
Hgb S cell lifespan
14 days
explain sickle cell crises
vaso-occlusion in capillaries
lower oxygen levels increase sickling
other blood cells & coagulation cascade activated
cell masses obstruct vessels can cause necrosis
adults tend to have autosplenectomy due to infarction, so splenomegaly is rare
sickle cell
what do inclusions on a PB smear of a sickle cell pt indicate?
autosplenectomy
complications of sickle cell
- growth of hands, hips, arms, legs affected
- lung and abdominal infarcts
- hepatomegaly
- leg ulcers near ankles
cell found on virtually any hemoglobinopathy smear, even a heterozygous trait
target cells
sickle cell disease on PB
- sickle cells
- target cells
- nRBCs
- polychromasia
- aniso & poik
- leukocytosis with left shift
- HJ bodies
sickle cell disease lab results
- low H&H
- ↓ osmotic fragility
- positive sickle solubility test (except newborns)
- Hgb electrophoresis—no A, mostly S, increased A2 and F
sickle cell disease tx
- pain relief
- rehydration
- antibiotics for secondary infections
- exchange transfusions
- hydroxyurea (↑ Hgb F)
𝛼2β2 6 lys
Hgb C
usually asymptomatic but may experience joint and abd pain, and splenomegaly
Hgb C disease
Hgb C disease on PB
- Hgb C crystals
- target cells
- aniso
- folded/convoluted RBCs
Hgb C disease RBC lifespan
30-55 days
𝛼2 βS βC
Hgb S/C
sickling and crystal formation
Hgb S/C
symptoms like mild sickle cell, with prominent splenomegaly
Hgb S/C disease
Hgb S/C on PB
- normo/normo
- Hgb concentrated on one side of cell “billiard balls”
- small, dense, misshapen cells with crystals
𝛼2β2 121 gln
Hgb D
most common in Indians
also African Americans
Hgb D
hemoglobinopathy requiring acid electrophoresis to distinguish, because the 2 bands migrate together
Hgb S/D
𝛼2β2 26 lys
Hgb E
most common in Southeast Asians as well as African Americans
Hgb E
2nd most prevalent hemoglobinopathy worldwide
Hgb E
↓ oxygen affinity of a given Hgb —– the effects of anemia
↓
hemoglobinopathy that may protect against malaria
Hgb E
Hgb E on PB
- micro/hypo
- target cells
most clinically significant types of thalassemia
those affecting alpha or beta chains
Thalassemia phenotype
βO/βO
O means absent
β-thalassemia major
Thalassemia phenotype
βO/B+
β-thalassemia major/intermedia
Thalassemia phenotype
β+/β+
β-thalassemia major/intermedia
Thalassemia phenotype
βO/β
β-thalassemia intermedia/minor
Thalassemia phenotype
β+/β
β-thalassemia minor
Thalassemia phenotype
βSC/β
β-thalassemia minima
(silent carrier)
Cooley’s anemia
β-thalassemia major
attempts to compensate for β-thalassemia major, but has a higher affinity for O2
Hgb F
what happens to excess alpha chains in beta thalassemia?
form 𝛼4 aggregates
precipitate in normoblast, damaging membrane
causes severe chronic hemolytic anemia
occurs in infants as failure to thrive
jaundice
hepatosplenomegaly
β-thalassemia
around time of switch from 𝛾 to β chains
manifestations of β-thalassemia
- infant failure to thrive
- jaundice
- hepatosplenomegaly
- siderosis
- “hair on end” bone structure
- thick jaw, concave nose
β-thalassemia CBC
- low H & H
- micro/hypo
- MCV in 50s or 60s
- retics normal or low
- RBCs may be elevated
β-thalassemia on PB
- target cells
- micro/hypo
- marked aniso, poik
- nRBCs
- variable basophilic stippling
- polychromasia
micro/hypo anemia with slightly decreased hgb, MCV in 50-70 range, and high RBC count (>5)
β-thalassemia minor
homozygotes have 100% Hgb F
micro/hypo anemia
𝜹β-thalassemia
hereditary persistence of fetal hemoglobin is a form of…
β-thalassemia
100% Hgb F with ↑ RBC count and ↑ Hgb
HPFH
2 types of HPFH on Kleihauer-Betke stain
populations associated
- Pancellular - most RBCs contain Hgb F - Black and Greek pop
- Heterocellular - 3% RBCs contain Hgb F - Swiss pop
normal 𝛼 chain combined with abnormal 𝜹β chain resulting from genetic crossover
Hgb Lepore
how does Hgb Lepore lead to anemia?
𝜹β chain is synthesized at a slow rate, leading to hematologic changes that resemble thalassemia
major Hgb seen with Hgb Lepore disease
Hgb F
tx for β-thalassemias
- splenectomy
- regular transfusions
- iron chelating agents
4 clinical phenotypes of 𝛼-thalassemia
- hydrops fetalis
- Hgb H disease
- 𝛼-thal minor
- silent carrier
Thalassemia phenotype
(–/–)
hydrops fetalis
Thalassemia phenotype
(–/-𝛼)
Hgb H disease
Thalassemia phenotype
(–/𝛼𝛼)
(-𝛼/-𝛼)
𝛼-thal minor
Thalassemia phenotype
(-𝛼/𝛼𝛼)
silent carrier
𝛾4
(no 𝛼 to combine with)
Hgb Barts
sickling Hgb
population associated with hydrops fetalis
Asian
β4
(no 𝛼 to combine with)
Hgb H
Hgb H disease on PB
- micro/hypo
- target cells
- ↑ retic
- nRBCs
inclusions can be seen by staining with brilliant cresyl blue, showing golf ball appearance
Hgb H
MCV 50-60
RBC >5
occasional Hgb H inclusions
𝛼-thal minor
