HEMOGLOBINOPATHIES Flashcards
- Most common genetic diseases, affecting approximately 7% of world’s population
- Qualitative defect of hemoglobin due to altered amino acid sequence within the globin chains
HEMOGLOBINOPATHIES
HEMOGLOBINOPATHIES:
Confirmatory test:
HPLC
Hb Electrophoresis
Hb Electrophoresis
_____ (pH 8.4)
_____ (pH 6.0 - 6.2)
Cellulose acetate
Citrate agar
All hemoglobin will migrate towards anode
Cellulose Acetate Agar
Cellulose Acetate Agar
Normal result:
A, A2, F
Normal hemoglobin that is fastest/ nearest to anode
A
Normal hemoglobin that is fastest/ nearest to anode is A followed by __
F
Slowest to migrate
A2
Cellulose Acetate Agar
Abnormal hemoglobins:
S, D, G, C, E, O
Performed when you want to separate hemoglobin S,D,G,C,E,O from S
Citrate Agar
S is separated from _ and _
D
G
C is separated from _ and _
E
O
Qualitative defect of hemoglobin
Hemoglobinopathies
Quantitative defect of hemoglobin
(absent or lacking globin
chain)
Thalassemia
Valine replaces glutamic acid at the 6th position of the beta chain
HEMOGLOBIN S
HEMOGLOBIN S:
____ replaces Glutamic acid at the ___ position of the ___ chain
Valine
6th
beta
Sickle Cell trait -
Hb As
- Generally asymptomatic or has mild symptoms only
- Normal RBC morphology, with the exception of a few target cells
Sickle Cell trait - Hb As
- Most common form of hemoglobinopathy
- Patients are either homozygotes (SS) or compound heterozygotes (SC, SE, S-B-thal)
Sickle cell disease
HEMOGLOBIN S:
Pathophysiology:
- Less soluble forming ____ or liquid crystals and causes sickling of RBCs
- ____ blood viscosity and ______ slow the blood flow
- Occlusion of capillaries and arterioles by sickled RBCs and infarction of
surrounding tissue
- _______ damages the membrane channels in RBC
tactoids
Increased
sickle cell formation
Hb S polymerization
HEMOGLOBIN S
Pathophysiology:
* Less soluble forming tactoids or liquid crystals and causes sickling of RBCs
___% O2 saturation among homozygotes
___% O2 saturation among heterozygotes
< 85%
< 40%
Hallmark of SCD, which accounts for most hospital and emergency department visits
Vaso occlusive crisis
T or F
HEMOGLOBIN S:
Painful episodes manifest often in bones, lungs, liver, spleen, eyes, CNS, urinary tract
T
HEMOGLOBIN S
Clinical Features:
- Sudden trapping of blood in the spleen, which leads to a rapid decline in hemoglobin
- Repeated splenic infarcts produce scarring resulting in diminished splenic tissue, abnormal function or gradual loss of splenic function
(autosplenectomy)
Splenic sequestration and infarcts
HEMOGLOBIN S
Clinical Features:
- Acute infections are common causes of hospitalization and have been the most common causes of death, especially in the first 3 years of life
Bacterial infections
HEMOGLOBIN S
Clinical Features:
Most common life-threatening hematologic complications and are usually associated with parvovirus infection
Aplastic episodes (BM failure)
HEMOGLOBIN S
Laboratory Screening Tests:
Slide method (+) result: Sickling of RBCs
2% Sodium metabisulfite test
HEMOGLOBIN S
Laboratory Screening Tests:
Tube method (+) result: Turbidity
Dithionite solubility test
2% Sodium metabisulfite test - Slide method (+) result:
Sickling of RBCs
Dithionite solubility test - Tube method (+) result:
Turbidity
LYSINE replaces glutamic acid at the 6th position of beta chain
HEMOGLOBIN C
HEMOGLOBIN C:
____ replaces glutamic acid at the __ position of ____ chain
LYSINE
6th
beta
Found almost exclusively in the African American population
HEMOGLOBIN C
Most common non-sickling Hb variant encountered in the United States
HEMOGLOBIN C
Hb C forms polymers intracellularly (short, thick crystals); increased in number of
_____
target cells
hexagonal crystals/”bar of gold” appearance
Thick crystals
associated with liver disease, Thalassemia, Hgb C disease
Target cells
T or F
Hgb C is milder disease compared with SCD since vaso-occlusive crisis does not occur
T
LYSINE replaces glutamic acid at the 26th position of beta chain
HEMOGLOBIN E
HEMOGLOBIN E:
___ replaces glutamic acid at the ____ position of __chain
LYSINE
26th
beta
The homozygous state (Hb EE) manifests as a mild anemia with microcytes and target cells
HEMOGLOBIN E
LYSINE replaces glutamic acid at the 121st position of beta chain
HEMOGLOBIN O-ARAB
HEMOGLOBIN O-ARAB:
___ replaces glutamic acid at the ____ position of ___ chain
LYSINE
121st
beta
Rare disorder found in Kenya, Israel, Egypt, and Bulgaria
HEMOGLOBIN O-ARAB
TYROSINE replaces histidine in the α, β, or γ chains
HEMOGLOBIN M
HEMOGLOBIN M:
_____ replaces ___in the α, β, or γ chains
TYROSINE
histidine
iron in the ferric state (Fe3+) and is unable to carry oxygen, which produces cyanosis
HEMOGLOBIN M
HEMOGLOBIN M:
iron in the ____ state and is unable to carry oxygen, which produces _____
ferric
cyanosis
GLUTAMINE replaces glutamic acid at the 121st position of beta chain
HEMOGLOBIN D
HEMOGLOBIN D:
_____ replaces glutamic acid at the ___ position of ____ chain
GLUTAMINE
121st
beta
LYSINE replaces asparagine at the 68th alpha chain
HEMOGLOBIN G
HEMOGLOBIN G:
____ replaces asparagine at the ____ ____chain
LYSINE
68th
alpha
