HEMOGLOBINOPATHIES

ABNORMAL / NON-FUNCTIONAL HEMOGLOBIN

A. ABNORMAL HEMOGLOBIN PIGMENTS
-They do not participate in O2 & CO2 exchange
1. Carboxyhemoglobin (HbCO)
-Reacts with CO
-The affinity for CO is 218x greater than O2 at 37 degree Celsius
-Not capable of transporting O2, hypoxia result and death may occur
-Produces a cherry red color of patients blood
-Irreversible reaction
-Concentration in non-smoker is 0-2.3%
-Among smokers 2.1-4.2 %
2. Sulfhemoglobin (SHb)
-Irreversible (0-2.2%)
-Critical level is 0.5g/dl
-Formed when H2S is added in the blood
-The conditions is generally benign
-Significant effect is cyanosis
-Formed among patient receiving sulfonamide and acetanilid
-Tinge of mauve lavender or greenish color
-100x less affinity with O2
-Peak absorption at 620nm

3. Methemoglobin (HbHi)
-Also known as ferrihemoglobin, oxidized hemoglobin, hemiglobin.
-Reaction is reversible, since methemoglobin is unstable
-Around 1% in children and normal adult
-Critical level is 1.5g/dl
-Gives chocolate brown color or Bluish color
-Reversibility may also be, because of NADH (Nicotinamide Adenine Dinucleotide
Dehydrogenase) enzyme.
-Peak absorption at 620-640nm
TYPES OF METHEMOGLOBINEMIA
A. Inherited Methemoglobinemia due to deficiency of NADH methemoglobin reductase.
B. Acquired Methemoglobinemia abnormal and toxic methemoglobin production due to
variety of substances ingested or absorbed including:
Anti malarial drug
Therapeutic drugs (Sulfonamide)
Drugs of abuse
Aniline dyes
Nitrate rich water
Aromatic chemicals
C. Inherited HbM Methemoglobinemia due to hemoglobin M variants as a result of amino
acids substitution in globin chains.

B.ABNORMAL HEMOGLOBIN VARIANTS

1. HbS

-Causes sickling of RBC

-2Alpha 2 Beta

-On which the glutamic acid on the 6th position of B chain is replaced by Valine

-Common to blacks

-Homozygous state cause sickle cell anemia

-Heterozygous state shows sickle cell trait

6Valine

2. HbC

-Formed among blacks and rare among whites

-2Alpha2 Beta2 6Lysine

-Appears also in homozygous and heterozygous states.

-If present they demonstrate a target cell

3. HbD

-Most common form of HbD are

-HbD Punjab (India), HbD Los Angeles (USA)

-Both with alpha and beta chain abnormality.

-Shows no sickling of RBC

4. HbE

-Associated with thalassemia

-2Alpha2 Beta 26Lysine

5. HbH

-No alpha chain

-Contains 4 beta polypeptide chains

-Reduce Alpha globin chains synthesis and excess B chain

-Forming B4 tetramer (Beta tetramer)

6. HbG
Identified in Ghana
Defect in the alpha chain
HbG-Philadelphia variant
Alpha 68asparagine to Lysine

7. HbSC

-Combination of 2 abnormal B chain hemoglobin

-Common among blacks with 85% target cells in pheripheral blood

8. HbSD

-Very rare, but resembles HbSC disease when found.

9. HbM

-Hb associated with methemoglobinemia

-Cyanosis is seen in HbM disease with alpha chain abnormality

-But does not appear until early 6 months of age in HbM variants with B chain
abnormality

10. Hb Chesapeake

-With alpha chain abnormality

-Associated with mild asymptomatic polycythemia

-With increase affinity with O2

-With significant elevated hematocrit

11. Hb Kansas

-Low affinity hemoglobin

-With cyanosis since infancy

-With normal O2 tension

-With reduced O2 saturation

-B 102 asparagine to threonine

-2Alpha2 Beta

12. HbO-Arab

-A rare disorder found in Kenya, Israel, Egypt, and Bulgaria

-Around 0.4% among African-Americans

-No clinical symptoms except splenomegaly

-Defects in B-chain 121-glu-lysine

-2Alpha2 Beta 121Lysine

13. HbC Harlem/ HbC Georgetown (HbCH)

-With double substitutions on the Beta-chain

-2Aplha 2Beta

6 Glutamic acid Valine

73 Aspartic acid Asparagine

14. Barts Hb

-Compose of 4 gamma chains

-This is an excess gamma chain in fetal life

15. HbI

-An inherited hemoglobin anomaly

-With defective alpha chain

-Alpha16Lysine instead of Glutamic acid

-Also HbI Philadelphia

-First identified among African-american family in North Carolina

-Rare hemoglobin

16. Hb Lepore

With normal alpha chain but with two betadelta globin fusion chain

Alpha Chain Defect

-HbD
-HbH (None)
-HbG
-HbM
-HbChesapeake
-HbI

Beta Chain Defect

-HbS
-HbC
-HbD
-HbE
-HbH(excess)
-HbSC
-HbSD
-Hb Kansas
-Hb O-Arab
-Hb C Harlem / Georgetown