Question

2.- State the type of normal adult hemoglobin and list other types present with various hemoglobinopathies

3.- Describe the general principle of and sources of error associated with CLIA-waived testing of hemoglobin

4.- Evaluate the concept of the hematocrit.

Answer 1

2) General Features of Hemoglobin

-->An O2-carrying protein organized as a TETRAMER, composed of:

1)2 alpha-globin polypeptides (**Always will be there**)

2)2 other chains (either Beta Globin, Gamma Globin, or Delta Globin)

-->4 Normal Types of Hemoglobin:

α2 β 2 (HbA; normal adult hemoglobin),

α2 γ2 (HbF; fetal hemoglobin),

α2δ 2 (HbA2; a minor adult hemoglobin)

α 2 β 2-glucose ( HbA(1c), Gycolated Hemoglobin)

-->HbF, HbA2, HbA(1c) are all considered **Minor Hemoglobins**

#. Features of HbA (Normal Adult Hemoglobin)

-->Is the major type of hemoglobin found in adults (90%)

-->Typically written HbA1

#. Features of HbF (Fetal Hemoglobin)

-->A tetramer consisting of 2 alpha chains & two gamma chains

1)The gamma chains are members of the BETA GLOBULIN FAMILY

-->Represents the major hemoglobin found in the FETUS & NEWBORN

-->Accounts for **60%** of the total hemoglobin in the RBC

-->HbF has a HIGHER AFFINITY for oxygen than HbA because 2,3 BPG DOES NOT BIND AS WELL to HbF then it does to HbA (i.e. the deoxy form of hemoglobin IS NOT STABALIZED)

#. Features of HbA2 (Minor Adult Hemoglobin)

-->Represents a minor component of normal adult hemoglobin (~2.5%)

-->First Appears about 12 weeks AFTER BIRTH

-->Is composed of 2 alpha globin chain

#. Features of Glycated Hemoglobin (HbA(1c) )

-->Represents the most glycosylated hemoglobin

1)Formed when blood glucose glycates the episilon-amino group of **LYSINE RESIDUES** and the amino terminals of hemoglobin

-->The level of HbA(1c) reflects the MEAN BLOOD GLUCOSE CONCENTRATION over the preceding 6-8 wks.

1) The normal fraction of hemoglobin glycated is normally ~6%

-->The measurement of HbA (1c) provides valuable information for the management of DIABETES MELLITUS

#. Hemoglobinopathy :-

inherited disorders in which mutations in or near multiple genes alter either the structure or the rate of synthesis of a particular globin chain.

The two types of hemoglobinopathies and the genetic abnormality associated with them

These disorders are divided into hemoglobinopathies, in which the amino acid sequence is altered, and the thalassemia syndromes, which are inherited disorders caused by gene mutations that reduce or completely preclude the synthesis of one or more of the globin chains.

#. Homozygous hemoglobinopathy

one in which if the alpha chains are affected by the disorder, both alpha chains would be abnormal. If the beta chains are affect by the disorder, both alpha chains would be abnormal. If the delta chains were affected by the disorder, both delta chains would be abnormal.

#. Heterozygous hemoglobinopathy

one in which if the alpha chains are affected by the disorder, only one of the two alpha chains is affected. If the beta chains are affected by the disorder, only one of the two beta chains is affected. What happens with heterozygous hemoglobinopathies is there is a decreased rate of synthesis of the abnormal globin chain and this makes for the formation of the abnormal hemoglobin. (The normal globin chain continues to be formed at the normal rate, the abnormal globin chain is formed at a lesser rate, the result is an abnormal hemoglobin being produced.)

#. Qualitative" hemoglobinopathy

Qualitative structural abnormalities involve a partial or complete replacement, an addition, or a deletion to one or more amino acids of the globin chains. The results of a change in the sequence will depend on the amino acids involved and their positions in the molecule.

3) The common principles of the hemoglobin test :-

-Collecting blood into the appropriate testing device.

-Hemolyzing the blood

-Analyzing the released hemoglobin by sending a light source through the specimen

-An optical reader receives the light after it passes through the specimen, allowing it to calculate the amount of hemoglobin in the specimen.

-The instrument then produces a digital readout expressed in grams per deciliter.

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