• Sickle cell disease is an inherited disorder in which red blood cells (RBCs) are
abnormally shaped.
• It is an autosomal recessive disease.
• Sickle-cell anemia is caused by a point mutation in the β-globin chain of hemoglobin,
causing the amino acid glutamic acid to be replaced with the less polar amino acid valine
at the sixth position.
• The β-globin gene is found on the short arm of chromosome 11.
• Under low oxygen conditions, the absence of a polar amino acid at position six of the β-
globin chain promotes the polymerization of hemoglobin, which distorts red blood cells
into a sickle shape and decreases their elasticity.
• The loss of red blood cell elasticity is central to the pathophysiology of sickle-cell
disease.
• Normal red blood cells are quite elastic, which allows the cells to deform to pass through
capillaries.
• In sickle-cell disease, low oxygen tension promotes red blood cell sickling and repeated
episodes of sickling damage the cell membrane and decreases the cell's elasticity.
• These cells fail to return to normal shape when normal oxygen tension is restored
consequently, these rigid blood cells are unable to deform as they pass through narrow
capillaries, leading to vessel occlusion and ischemia.
• In a carrier, the presence of the malaria parasite causes the red blood cell to rupture,
making the plasmodium unable to reproduce.
• Therefore, in areas where malaria is a problem, people's chances of survival actually
increase if they carry sickle-cell trait (selection for the heterozygote).
• Patients with sickle-cell anemia do not have correspondingly greater resistance to
falciparum malaria.
• Sickle cell can result in painful episodes, serious infections, chronic anemia, and
damage to body organs.
• These complications can, however, vary from person to person depending on the type of
sickle cell disease each has.
• Some people are relatively healthy and others are hospitalized frequently.
• The different forms of sickle cell disease are determined by the genes inherited from the
person's parents.
• Someone who has the disease has inherited a sickle cell gene from each parent
(hemoglobin SS disease also called sickle cell anemia)
• Someone who inherits only one sickle cell gene and a normal gene from the other parent
will have the sickle cell trait, but not the disease.
• A blood test can determine whether you have sickle cell disease or carry the sickle cell
trait.
• People with sickle cell, trait don't have sickle cell disease or exhibit any signs of the
disorder, but they can pass the gene for the disease to their children.
• When both parents have the sickle cell trait, there is a 25% chance that a child will have
sickle cell disease.
• But when one parent is carrying the trait and the other actually has the disease, the odds
increase to 50% that their child will inherit the disease.
 
Clinical Features of Sickle Cell Disease
• Symptoms of sickle cell disease vary and range from mild to severe, and symptoms may
be less severe or different in children who have inherited a sickle cell gene from one
parent and a different abnormal hemoglobin gene from the other.
• Most kids with sickle cell disease have some degree of anemia and might develop one or
more of the following conditions and symptoms as part of the disorder.
Acute Chest Syndrome
Inflammation or trapped red blood cells in the lungs cause this syndrome.
Features include chest pain, coughing, difficulty breathing, and fever
Hand-Foot Syndrome (also called Dactylitis)
This painful swelling of the hands and feet, plus fever, maybe the first sign of
sickle cell anemia in some infants.
Aplastic Crisis
This is when the bone marrow temporarily slows its production of RBCs due to
infection or another cause, resulting in a severe drop in the red cell count and
severe anemia
Signs include paleness, fatigue, and rapid pulse.
Haemolytic crises are acute accelerated drops in hemoglobin levels. The red blood
cells break down at a faster rate.
Painful Crises
These may occur in any part of the body and may be brought on by cold or
dehydration.
The pain may last a few hours or up to 2 weeks or even longer, and maybe so
severe that a child needs to be hospitalized.
Splenic Sequestration Crises
The spleen becomes enlarged by trapping (or ‘sequestering’) the abnormal RBCs.
This leads to fewer cells in the general circulation.
Early signs include paleness, weakness, an enlarged spleen, and pain in the
abdomen.
Stroke
Poor blood flow in the brain can occur when the sickle-shaped cells block small
blood vessels. This may lead to a stroke.
Signs can include headache, seizures, weakness of the arms and legs, speech
problems, a facial droop, and loss of consciousness.
 
Other possible complications include leg ulcers, bone or joint damage, gallstones,
kidney damage, painful prolonged erections in males (priapism), eye damage, and
delayed growth.
 
Management of Sickle Cell Disease
Diagnosis
• When sickle cell disease or anemia is suspected refer the patient to the hospital for the
confirmation of a disease. At the hospital, the confirmation can be done by doing sickling
test.
• Sickling of the red blood cells, on a blood film, can be induced by the addition of sodium
metabisulfite.
• The presence of sickle hemoglobin can also be demonstrated with the ‘sickle solubility
test’
The mixture of hemoglobin S (Hb S) in a reducing solution (such as sodium dithionite)
gives a turbid appearance while normal Hb gives a clear solution.
• Abnormal hemoglobin forms can be detected on hemoglobin electrophoresis, a form of
gel electrophoresis on which the various types of hemoglobin move at varying speed.
• Sickle-cell hemoglobin (HgbS) and hemoglobin C with sickling (HgbSC)—the two
most common forms—can be identified from there.
• The diagnosis can be confirmed with high-performance liquid chromatography (HPLC)
• In HbSS, the full blood count reveals hemoglobin levels in the range of 6-8 g/dL with a
high reticulocyte count (as the bone marrow compensates for the destruction of sickle
cells by producing more red blood cells).
 
Treatment
• After confirming the diagnosis usually treatment is initiated at hospital depending on the
real situation.
• General management is aimed at alleviation of the symptoms and the promotion of life
style.
Hydration with i.v fluids
Analgesics e.g diclofenac
Antibiotic(s) if the crisis is due to infection
Regular folic acid supplementation (5mg daily) to support the greatly increased
erythropoietin activity.
Prophylaxis of malaria using chloroquine
• Painful crises are treated with hydration and analgesics, pain management requires opioid
administration at regular intervals until the crisis has settled.
• Aplastic crises, most patients can be managed supportively, some need a blood transfusion.
• Splenic sequestration crises are acute, painful enlargements of the spleen. The abdomen
becomes bloated and very hard. Management is supportive, sometimes with blood
transfusion.
• Haemolytic crises: Management is supportive, sometimes with blood transfusion.
Complications of Sickle Cell Disease
• Stroke can result from a progressive vascular narrowing of blood vessels, preventing
oxygen from reaching the brain.
• Cerebral infarction occurs in children and cerebral hemorrhage in adults.
• Risk of developing recurrent chest infection caused by encapsulated organisms such as
Streptococcus pneumoniae and Haemophilus influenzae.
• Avascular necrosis (aseptic bone necrosis) of the hip may occur as a result of ischemia.
• Priapism and infarction of the penis.
• Osteomyelitis (bacterial bone infection) in individuals with the sickle-cell disease is most
frequently caused by Salmonella, whereas Staphylococcus is the most common causative
organism in the general population.
• Autosplenectomy, because of its narrow vessels and function in clearing defective red
blood cells, the spleen is frequently affected.
• It is usually infracted before the end of childhood in individuals suffering from sickle-cell
anemia.
• the severity of anemia may induce high output failure, cardiomegaly, and flow
murmurs.
• Retinopathy, secondary to sequestration of blood in the conjunctival vessels are marked by
dilated and tortuous retinal vessels, microaneurysms, and retinal hemorrhage.
• Cholelithiasis, particularly in patients older than 6 years, can occur due to chronic
hemolysis.
• Irreversible renal damage may progress to renal failure requiring transplantation.
• Haematuria due to sickling in the vas recta or renal papillary necrosis is common.
Patient Education
• Patient's families should have genetic counseling and education regarding clinical
manifestations associated with the disorder and its complications.
• Reinforcement should occur incrementally during the course of ongoing care.
• Families should be educated on the importance of hydration, diet, outpatient medications,
and immunization protocol.
• Patients should be instructed on proper splenic palpation and observation of pallor,
jaundice, and fever.                                                                                         
REFERENCES;
•      Braunwald & Fauci (2001). Harrison’s principles of internal medicine 15th Ed.  Oxford: McGraw Hill
•      Davidson, S (2006). Principles and practice of medicine 20th Ed.  Churchill: Livingstone.
Kumar & Clark (2003) Textbook of clinical medicine. Churchill: Livingstone.
•      Douglas Model (2006): Making sense of Clinical Examination of the Adult patient. 1st Ed. Hodder Arnold
•      Longmore, M., Wilkinson, I., Baldwin, A., & Wallin, E. (2014). Oxford handbook of clinical medicine. Oxford
•      Macleod, J. (2009). Macleod's clinical examination. G. Douglas, E. F. Nicol, & C. E. Robertson (Eds.). Elsevier Health Sciences.
•      Nicholson N., (1999), Medicine of Non-communicable diseases in adults. AMREF
•      Stuart and Saunders (2004): Mental health Nursing principles and practice. 1st Ed. Mosby
•      Swash, M., & Glynn, M. (2011). Hutchison's clinical methods: An integrated approach to clinical practice.