Practical Clinical Hematology 4 Sickle Cell

What is Sickle cell: Sickle cell anemia is an inherited disorder that leads to the production of an abnormal hemoglobin variant, hemoglobin S (HbS) Hemoglobin S production arises from an altered (mutated) “S” gene. Differ on Hb A by one amino acid substitution. .

Amino acid substitution in HbS

SS gene (homozygous SS) One S gene Sickle cell anemia, 80% to 100% of the hemoglobin is HbS Sickle cell trait, 20% to 40% of the hemoglobin is HbS No symptoms under 'normal' conditions. Does not have any health problems But in 'sickling crises' such as infection or dehydration There is some symptom like haemolytic anaemia (jaundice)

RBCs have Hbs In the RBC, variant Hbs can form polymers in low oxygen conditions, changing the shape of the RBC from a round disc to a characteristic crescent (sickle) shape. This altered shape limits the RBC’s ability to flow smoothly throughout the body, limits the hemoglobin’s ability to transport oxygen, and decreases the RBCs lifespan from 120 days to about 10-20 days.

The affected person can become anemic because the body cannot produce RBCs as fast as they are destroyed. Also, sickled blood cells can become trapped in blood vessels reducing or blocking blood flow. This can damage organs, muscles, and bones and may lead to life-threatening conditions.

Hydroxyurea as a treatment HbF, also called fetal hemoglobin, is the form of hemoglobin present in the fetus and small infants. Most HbF disappears early in childhood, although some HbF may persist. Fetal hemoglobin is able to block the sickling action of red blood cells. Because of this, infants with sickle cell disease do not develop symptoms of the illness until. HbF levels have dropped. Adults who have sickle cell disease but still retain high levels of hemoglobin F generally have mild disease. Hydroxyurea (Droxia) is a drug that reduces the severity of sickle cell disease by stimulating production of HbF. It is currently the only drug in general use to prevent acute sickle cell crises

Sickle cell test: A sickle cell test is a blood test done to screen for sickle cell trait or sickle cell disease. There are three method A saline citrate with paraffin oil. Sodium Metabisulfite Method. Solubility Test.

General Principle We will make the conditions at which oxygen tension decline to induced the sickling process of Hbs in RBCs.

A saline citrate with paraffin oil Principle: a saline citrate suspension of blood is allowed to stand in a test tube under a layer of paraffin oil until sickling takes place.’ In employing any of the common diagnostic tests for sickling it is desirable to obtain blood which has a low. fraction of oxyhemoglobin.

Sodium Metabisulfite Method Principle When a drop of blood is sealed between a cover slip and a slide, the decline in oxygen tension due to oxidative processes in the blood cells leads to sickling. In this method added with blood drop a chemical reducing agents. Such as sodium metabisulfite. This rapidly reduces oxyhemoglobin to reduced hemoglobin, then this will be accelerate sickling .

Solubility test Principle Erythrocytes are lysed by saponin and the released hemoglobin is reduced by sodium hydrosulfite in a concentrated phosphate buffer. Under these conditions, reduced HbS is characterized by its very low solubility and the formation of crystals.

Principle The presences of HbS or HbC are indicated by the turbid solutions. The normal HbA under these same conditions results in a clear non-turbid solutions.

Discussion The sickle cells or the holly-leaf form of the cell must come to a point or points to be considered positive. Elongated cells with a round end must not be confused with sickle cells. Sickling of the cells is maximum at 37oC and decreased as the temperature lowers. This test should not be performed on infants less than six months old. With this method it is not possible to distinguish sickle cell trait from sickle cell disease. Hence if the test is positive, it is advisable to perform hemoglobin electrophoresis to determine the presence of the trait or the anemia and to positively identified the type of the sickling hemoglobin present.