Sickle cell disease is a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. People with this disorder have atypical hemoglobin molecules called hemoglobin S, which when reduced can distort red blood cells into a sickle, or crescent shape. HB-S is much less soluble than normal hemoglobin particularly in reduced state.
In people with sickle cell disease, at least one of the beta-globin subunits in hemoglobin is replaced with hemoglobin S. In sickle cell anemia, which is a common form of sickle cell disease, hemoglobin S replaces both beta-globin subunits in hemoglobin. In other types of sickle cell disease, just one beta-globin subunit in hemoglobin is replaced with hemoglobin S. The other beta-globin subunit is replaced with a different abnormal variant, such as hemoglobin C. For example, people with sickle-hemoglobin C (HbSC) disease have hemoglobin molecules with hemoglobin S and hemoglobin C instead of beta-globin. If mutations that produce hemoglobin S and beta thalassemia occur together, individuals have hemoglobin S-beta thalassemia (HbSBetaThal) disease.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
SCD is known to have originated as part of mankind’s fight against malaria many thousands of years ago. Having RBCs with Hb-S makes people more resistant to infection with malaria. This is particularly an advantage to people with one SCD gene, who have an in-built resistance to malaria and at the same time have no problems associated with carrying one gene. This in-built resistance to malaria is the reason why SCD is particularly common in parts of Kenya where malaria is also common, such as the Coast and Western Kenya. However, migration means that the condition can be found anywhere in the country.
This is the asymptomatic healthy carrier state for Hb-S. It represents the heterozygous state for the Hb-S gene, the patient inheriting one gene for Hb-S from one parent, and one gene for normal hemoglobin (Hb-A) from the other parent. The red cell hemoglobin consists of 25 to 45% Hb-S and 55 to 75% Hb-A. The cells do not contain sufficient Hb-S for them to undergo sickling at the lowest oxygen tension occurring in the body. the lifespan of the rbcs is normal. In stained blood film there are no sickle cells and apart from the few target cells the red cells appear normal. SCT does not cause anaemia although it occasionally causes haematuria. There is good evidence to suggest Hb-S confers relative resistance to P.falciparum thus causing the persistence and high frequency of the Hb-S gene in areas where malaria is endemic.
SICKLE- CELL ANAEMIA
This represents the homozygous state for the Hb-S gene, the patient receiving one Hb-S gene from each parent, both of whom show sickle cell trait. The cells contain sufficient Hb-S for sickling to be produced in vivo by the reduction of oxygen tension which occurs in the capillaries. The in vivo sickling is responsible for the clinical manifestations of the disease.
The diagnosis is usually but not invariably made in childhood, often before the age of 2 years. Clinical manifestations are rare in the first 6 months of life. This is due to production of Hb-F, primary hemoglobin produced by the fetus, decreases sharply after birth and reaches adult levels by 1-2 years of age.
Clinical manifestations include (1) chronic hemolytic anaemia (2) vascular obstruction. Chronic hemolytic anemia results from the short life span of sickle cells. Reduced Hb-S have high viscosity which results in slowing of circulation, with impaction of sickle cells, often causing thrombosis(Thrombosis is the formation of a blood clot, within a blood vessel) .this results in ischaemia and sometimes in necrosis of part of the organ or tissue involved.
The most common symptoms are those of anaemia i.e. fatigue, weakness, irritability and dyspnoea. The crises are other characteristic feature which consists of attacks of bone and joint or abdominal pain, often with fever. Abdominal pain is commonly severe and is accompanied by nausea vomiting and leucocytosis. Gall stones are common and can occasionally cause cholecystis. Obstruction of cerebral vessels occasionally causes nervous system manifestations which include headaches, paralysis, convulsions and psychic changes
This is done by demonstration of sickling phenomenon in vitro. Blood is mixed on a slide with chemical reducing agent e.g. sodium metabisulphite; it is covered with a cover slip and sealed completely then incubated for 1hour at 37 degrees.
This test does not differentiate between SCD and SCT. Positive tests should be confirmed by Hb electrophoresis.
Sickle cells can also be observed in blood stained films.
Sickle cells can also be observed in blood stained films.
Prognosis is serious; many patients die in the first decade. Once a patient has passed critical years of childhood and adolescence, the prognosis is better even up to 4th or5th decade.
Bone marrow transplant, also known as stem cell transplant, offers the only potential cure for sickle cell anemia. It’s usually reserved for people younger than age 16 because the risks increase for people older than 16. Finding a donor is difficult, and the procedure has serious risks associated with it, including death.
As a result, treatment for sickle cell anemia is usually aimed at avoiding crises, relieving symptoms and preventing complications. Babies and children age 2 and younger with sickle cell anemia should make frequent visits to a doctor. Established infections should be treated promptly with appropriate antibiotics. Transfusion is indicated only when anemia causes troublesome symptoms. Childhood vaccinations are important for preventing disease in all children, and more important for children with sickle cell anemia because their infections can be severe.
Scientists are studying new treatments for sickle cell anemia, including: