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Clinical Significance Of Sickle Cell Disease As a Major Hemoglobinopathy

Updated on January 20, 2014

A Sickle Cell Patient

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Introduction

This is the most widespread hemoglobinopathy. In Africa, its epidemiology is unique and very popular, cutting across the sahara regions (especially west African regions) and affecting more than 30% of the populace of these Nations. Hemoglobin S offers partial protection against falciparum malaria (balanced polymorphisms). The genetic variants are:

The genetic variants Of Hemoglobin

 
 
Sickle cell anemia
Homozygous S-S
Sickle cell trait
Heterozygous A-S
Hemoglobin S-thalasemia
Heterozygosity between sickle cell hemoglobin and thalasemia
Hemoglobin S-C disease
Heterozygosity between S and C

The Sickled Shaped Blood Cells

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Pathology

Hemoglobin S is formed by the substitution of valine in place of glutamic acid in the sixth residue of the beta chain of adult hemoglobin. Hemoglobin S is soluble in the oxygenated state and the red cells containing it maintain normal shape and function. Under conditions of lowered oxygen tension, it forms liquid crystals (tactoids) which distort the erythrocytes to assume the characteristic sickle shape. Such cells are rigid and they obstruct the microcirculation. This results in sludging and occlusion of the microcirculation which manifests as dysfunction of many organs. Generally, symptoms occur if the number of sickle cells exceeds 50% of the total. In Hb S-C disease and Hb S-D disease, the clinical severity is more. In Hb S-thalassemia, the presence of large amounts of Hb F protects against sickling. Sickled cells are easily destroyed and this leads to hemolytic anemia. Maximal lesions are seen in the heart, lungs, spleen, bone marrow, brain and placenta. Factors which precipitate sickling are hypoxia, acidosis, dehydration, fever and infections. Occlusion of the microcirculation resulting from sickling aggravates acidosis further, thereby establishing a vicious circle. Most of the clinical features can be explained on the basis of anemia, hemolysis, obstruction to microcirculation and siderosis of parenchymal organs.

Diagnosing Sickle Cell Disease

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Diagnosis, Prognosis And Prophylaxis

Diagnosis

In endemic areas, the clinical diagnosis can be easily confirmed by demonstrating the sickling phenomenon. One drop of blood is mixed with an equal volume of 2% sodium metabisulphite solution. A cover slip is applied and the edges are sealed with Vaseline after incubation at 370 for 30 minutes. Sickle cells are demonstrable. Sickling may occur with other hemoglobins also in some cases. Electrophoresis of Hb at pH 8.6 shows Hb S as a slow-moving band.

Course and prognosis

Majority of severe cases die in childhood before reaching five years of age. Only one-fourth live up to 30 years or more. Acute splenic sequestration, septicemia, meningitis and gastroenteritis account for most of the deaths. Pregnancy carries increased risk to mother and fetus.

Prophylaxis

These include;

  1. Screening of babies born to carriers of Hb S, with a view to make an early diagnosis and prevent crisis,
  2. Detection of an affected fetus by amniocentesis and termination of the pregnancy, and
  3. Genetic counseling to avoid marriage between heterozygotes.

A recessive Inheritance

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Clinical Manifestation

Sickle cell disease may present in different ways. Symptoms occur after the sixth month of age since the full complement of beta chains is not produced in the first few months of life. When the disease is severe, growth is retarded with delay in skeletal maturation giving rise to the characteristic picture of stunted growth, long limbs, narrow hips and exaggerated lordosis. Sickle cell crisis supervene frequently involving several organs, and untreated cases are fatal before the third decade. This extreme form is more common in Africans. In mild cases, there may be only mild anemia, growth and development being normal. This variety is more common in the Middle East. In India, the cases show an intermediate severity.

Early symptoms include anemia, hepatosplenomegaly, retardation of growth, recurrent infections and painful swellings of the hands. Crises are characterized by painful episodes associated with constitutional disturbances like fever, worsening of anemi andsymptoms referable to organ systems. Cardiomegaly, cardiac murmurs, pulmonary hypertension and cor pulmonale are late manifestations. Tender hepatomegaly may result from infarction of the liver. Infection may convert these infarcts into abscesses. Cholelithiasis and leg ulcers may develop.

The splenic sequestration syndrome is characterized by sudden painful splenomegaly associated with rapid fall in hemoglobin and hypotension. This is seen more frequently in children. The condition may be fatal if left untreated. As a result of repeated infarction, the spleen may shrink and be converted into a fibrous streak. This is referred to as autosplenectomy. The infarcts may become calcified. The spleen becomes impalpable in sickle cell anemia by the age of 10-12 years. In other sickle cell syndromes such as S-thalassemia, S-C and S-D, the spleen remains palpable throughout life.

Renal involvement manifests as hematuria, hyposthernuria, acute nephritis or occasionally nephritic syndrome. Priapism may occur due to obstruction to corpora cavernosa. Skeletal symptoms are common. These include bone pain, arthralgia, backache, dactilitis, salmonella osteomyelitis and multiple bone infarcts. Dactilitis is seen in young children. The femoral and humeral heads may undergo avascular necrosis. Neurovascular accidents develop due to occlusion of intracranial vessels. Blindness may develop due to repeated vitreous hemorrhages and retinal tears and detachment. Aplastic crises occur rarely and are characterized by the rapid development of severe anemia due to marrow hypoplasia and accelerated hemolysis.

Managing Sickle Cell Anemia

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Management

Aim of treatment is to prevent deterioration and avoid crises. The hemoglobin level should be maintained around 8 g/dl with the hematocrit around 25%. Since folic acid deficiency may develop in a few cases, supplementation of 1mg folic acid dailu is beneficial. Intercurrent infections should be treated promptly. Crisis have to be managed as emergencies with rest, sedation, maintenance of fluid and electrolyte and blood transfusions.

Transfuson or partial exchange transfusion may be needed during hemolytic or sickling crises. Several drugs such as nitrates, phenothiazines, corticosteroids, dextran, hyperbaric oxygen, anticoagulants and urea have been used for treating sickling crises with variable results. Intravenous injection of 2.0ml of 40% magnesium sulphate relieves pain.

Potassium cyanate has been tried with a view to increase the oxygen affinity of Hb S by carmanylation. This drug helps in increasing the lifespan of erythrocytes but its neurotoxicity limits its prolonged use. Bone marrow transplantation has been tried experimentally in a few cases with encouraging results.

© 2014 Funom Theophilus Makama

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