Disease
Mutation
Epidemiology
Hemoglobin content
Clinical Manifestation
Hb SS
6GluVal
ß-chain (both)
Hb As
6GluVal
ß-chain (one)
African
African American
Mediterranean
Middle East
African Americans – 8%
Mediterranean
Central Americans
Asians
Hgb A – 60%
Hgb A2 – normal
Hgb F – normal
Hgb S – 40%
- All organs are affected
- Generally Asymptomatic
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Under extreme hypoxic
conditions:
 Systemic sickling
 Vascular occlusion
 Pooling of sickled cells in the
spleen
 Focal necrosis in the brain
 Rhabdomyolysis
 Death
Severe hemolytic anemia
w/polychromasia
Normochromic, Normocytic
Anemia
RBC
Hgb Crystals
**Hgb A2 – approx. 2%
**Hgb F - <7%
**Hgb C - >90%
- Asymptomatic*
- No vasoocclusive crisis
- Problematic only if infection
occurs or if mild chronic
hemolysis leads to gallbladder
disease
- No specific treatment
required
Laboratory Diagnosis
Treatment
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Sickle cells
Target cells
Nucleated RBCs
Pappenheimer bodies
Howell-Jolly bodies
Hb E
26GluLys
ß-chain
Hb O-Arab
121GluLys
ß-chain
- Rare
West African – 17-28%
African American – 2-3%
*Hgb A – 60%
*Hgb A2 – normal
*Hgb F – normal
*Hgb C – 40%
Hgb A2 – variable
Hgb F – 20%
Hgb S – 80%
Tissue necrosis
Kidney failure
Hyposplenism
Joint swelling
Vascular occlusion
Hb C
6GluLys
ß-chain
- Rare
Mild to moderate anemia**
Normochromic, Normocytic
Normochromic, normocytic
Microcytosis, mild
hypochromia (occasionally)
 Target cells (marked increase)
 Nucleated RBCs (mod. increase)
 Reticulocytes (mod. Increase)
- Short, thick
Southeast Asia – 30%
Kenya
Israel
Egypt
Bulgaria
*Hb E – 30-40%
**Hb E - >90%
- Asymptomatic*
- severe clinical conditions
when inherited with Hb S
similar to those in Hb SS
 splenomegaly
 fatigue
 mild splenomegaly**
- No therapy
- Genetic counseling
- Generally none
Mild anemia**
 Slight erythrocytosis*
 Slight target cells*
 Target cells (few to many)**
 Microcytes**
 Normal retic count**
 Survival time is shortened**
- Polymerization does not
occur
- Mild hemolytic anemia
 Target cells (many)
- Polymerizes under low
oxygen tension
- Does not alter RBC shape to
the extent that Hb S does
Other parameters
 Increased bilirubin
 Decreased haptoglobin
Bone marrow erythroid
hyperplasia
+
 Hemoglobin solubility
screening test (+)
 Acid electrophoresis
Tests
(differentiated)
 Hemoglobin solubility
screening test (+)
 Hemoglobin solubility
screening test (-)
 HPLC
 Hemoglobin solubility
screening test (-)
 HPLC
 Hemoglobin solubility
screening test (-)
 HPLC
 Citrate Agar
Electrophoresis (separated)
*
 Citrate Agar
Electrophoresis (separated from
 Citrate Agar
Electrophoresis (the only hgb to
Hb C, migrates w/ Hb A, Hb O)
 Alkaline hemoglobin
electrophoresis (migrates w/ Hgb
D, Hgb G)
 Sickling begins at <85%
oxygen saturation
 Apparent immunity to P.
falciparum
 Crisis initiated by surgery,
trauma, pregnancy, high
altitude, etc.
 Diagnosis is made after 6
months of age
 Life expectancy w/proper
treatment is 50yrs or longer
 Death usually results from
infection/congestive heart
failure
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 Mean MCV (65gL)*
 Low MCV (55-65fL)**
* - heterozygous
** - homozygous
[in bold] – confirmatory test
 Cellulose Acetate
Electrophoresis (migrates w/ Hb
A2, Hb E, Hb O-Arab)
Additional Information
 Sickling begins at <40%
 Most common sickling
oxygen saturation
variant in US
 Apparent immunity to P.
 3rd most common in the
falciparum
world
 Most common
hemoglobinopathy in US
 Severe respiratory infections,
unpressurized flight at high
altitudes, and anesthesia
(where pH and oxygen levels
are sufficiently lowered to
cause sickling), patients may
develop splenic artifacts
**
 Cellulose Acetate
Electrophoresis (migrates w/Hb
C, Hb O, Hb A2)
 Causes abnormal alternative
splicing and decreased
transcription of functional
mRNA for the Hb E globin
chain
 Qualitative and quantitative
defect
 Resembles thalassemia
major*
 When combined with ßthalassemia becomes more
severe than Hb EE*
 Resembles thalassemia
trait**
 P. falciparum multiplies
more slowly**
slightly move towards the cathode)