Biomimetics

Result from the inheritance of one gene for HbS from one parent and one gene for HbC from the other parent. HbD has several variants. Both homozygous (22121 Glu Gln) and the heterozygous (211121 Glu Gln) states are asymptomatic.

The peripheral blood smear is undermarkable, except for a few target cells. Hemoglobin migrate electrophotecally to the same position as HbS and HbC at Alkaline PH but migrates with HbA at acid PH. HbD is non-sickling soluble hemoglobin.

HEMOGLOBIN E (HBE)

HbE results from the substitution of lysine for glutamic acid in the beta chain of Hb. It occurs with greatest frequency in Burma, Thailand, Cambodia, Laos, Malaysia and Indonesia. The homozygous state (22²⁶

Glu lys) presents with little anemia; target cells and microcytic hypochromic red cells. HbE trait (21126 ^Glu-lys) is asymptomatic clinically. There is microcytosis, target cells and approximately 70% HbA and 30% HbE and A2 on routine electrophoresis.

HEMOGLOBIN Oarab (HbOarab) DISEASE AND TRAIT HbOarab is rare hemoglobin variant that occurs infrequently in blacks Arab and Sudanese population. Homozygous HbOarab (22121 Glu lys) exhibits a mild hemolytic anemia with slight splenomegaly and target cells on the peripheral blood smear. This hemoglobin migrates electrophotecally with HbC, HbE and HbA2 at alkaline PH. In the heterozygous state of HbOarab (211121 Glu-lys) the patient is asymptomatic.

HEMOGLOBIN S WITH OTHER ABNORMAL HEMOGLOBIN

HEMOGLOBIN SB THALASSEMIA

Because of the increased frequency of both HbS and B-thalassemia genes in similar population groups, inheritance of both defects is relatively common.

Clinically, the disorder produces symptoms of moderate anemia and many signs of sickle cell anemia, which are usually less frequent and less severe.

Laboratory finding are mild to moderate microcytic anemia, some sickled RBCs on stained blood smear, and reticulocytosis. The HbA2 is > 3% Hbs predominates on electrophoresis and HbA is decreased or absent. Hbf increase is variable.

Treatment: Like sickle cell anemia.

HEMOGLOBIN SC DISEASE (HbSC)

HbSC is of intermediate severity between hemoglobin SS disease and hemoglobin CC disease. Patients may have a mild anemia, with hemoglobin ranging from 10 to 13 gm/dl and a reticulocytosis of 3 to 10%. In the peripheral smear, target cells are more prominent

than

sickled cells. Hemoglobin electrophoresis shows equal amounts of hemoglobin S and C. The clinical course varies from asymptomatic to severe.

HEMOGLOBIN SD DISEASE (HbSD)

HBSD is the combination of HbS and HbD. Because these hemoglobins migrate together at alkaline PH, the electrophoretic pattern is similar to that of SCA.

HEMOGLOBIN SOarab (HbSOarab)

The combination of HbS and HbOarab can have a clinical presentation that is similar in severity to that of SCA. The anemia is severe, with typical sickle cells seen on the peripheral blood smear. This condition might initially be confused with HbSC on routine electrophoresis;

however differentiation can be made with acid electrophoresis.

REVIEW QUESTIONS

1. Abnormal hemoglobin are most often caused by a. Amino acid substitutions

b. Amino acid deletion c. Globin chain elongation d. Globin chain fusion

2. Which one of the followings is not a characteristic of hemoglobinopathies?

a. Conditions in which abnormal hemoglobins are synthesized b. Result from inherited abnormalities or genetic mutation c. All are manifested in clinically significant conditions d. Result in a defect instructional integrity of function of the

hemoglobin molecule.

3. The most common cause of hemoglobinopathies is an abnormality in the --- globin chain

a. 

b. 

c. 

d. 

4. What factors contribute to the sickling of RBCs?

a. Increase in PH and oxygenation

b. Decrease in PH and oxygenation and dehydration c. Increase in PH and decrease in oxygenation

d. Decrease in dehydration and increase in PH and oxygenation 5. What are the therapeutic goals in the treatment of sickle cell anemia?

a. Decrease microvascular entrapment of sickle cells or change the volume of RBCs

b. Modify oxygen affinity or solubility of sickle hemoglobin c. Increase production of fetal hemoglobin

d. All of the above

6. Laboratory values that could be found in a patient with sickle cell anemia

(HbSS) disease includes all of the following except:

a. 40% HbS on cellulose acetate electrophoresis b. 7% HbA2 on cellulose acetate electrophoresis c. Normocytic, normochromic anemia

d. Hemoglobin 6.0 g/dl

7. Cellulose acetate hemoglobin electrophoresis is run at a (an)

a. Alkaline PH

b. Acid PH

c. PH gradient

d. Alkaline and acid PH

8. The condition (s) associated with increased levels of HbF is (are)

a. Infancy

b. Hemoglobinopathies c. Thalassemia

d. All of the above

9. Two HbS that migrates together on cellulose acetate electrophoresis at alkaline PH are a. A1 and A2

b. A1 and E c. S and C d. S and D

The thalassemias are a heterogenous group of disorders with a genetically determined reduction in the rate of synthesis of one or more types of the normal hemoglobin polypeptide chain. This results in a decrease in the amount of the hemoglobin involving the affected chain.

Classification

There are two main groups of thalassemia:

1. Alpha thalassemia, affecting the synthesis of alpha chain 2. Beta Thalassemia, affecting the synthesis of Beta chain 1. Alpha thalassemia:

Single gene deletions give rise to the so-called silent carrier state and the person is normal, both clinically and hematologically.

Table 6.1: -Thalassemia syndrome : Phenotype , Genotype

Phenotype Genotype Abbreviation

Normal Normal  

Silent carrier of  thalassemia Heterozygous ⁰  ⁺

 -Thalassemia trait Heterozygous ⁰  ⁰

 -Thalassemia trait Homozygous ⁺ ⁺ ⁺

Hemoglobin H disease Copmpound

heterozygous ⁺ ⁰ ⁰ ⁰ Hemoglobin Bart’s hydrops fetals Homozygous ⁰⁰ ⁰⁰