Sickle cell anemia

Question 1

Sickle Cell Anemia (slide)

Answer 1

abnormal hemoglobin (hemoglobin S [HbS]) = chronic hemolytic anemia, pain, organ failure.

recessive inheritance

“sickled” when deoxygenated… returns to normal shape with oxygenation… can be permanent after repeated episodes.

Question 2

Sickle Cell Disease is an:

Answer 2

inherited disorder in which an abnormal hemoglobin (hemoglobin S [HbS]) leads to chronic hemolytic anemia, pain, and organ failure. The HbS gene is transmitted by recessive inheritance and can manifest as sickle cell trait or sickle cell disease.

Question 3

Etiology and Pathogenesis of Sickle cell anemia:

Answer 3

the abnormal structure of HbS results from a point mutation in the beta chain of the hemoglobin molecule with an abnormal substitution of a single amino acid, valine, for glutamic acid. Variations in proportions exist, and the concentration of HbS correlates with the risk of sickling.

Question 4

When does the HbS become sickled?

Answer 4

in the homozygote with sickle cell disease, the HbS becomes sickled when deoxygenated or at a low oxygen tension. The deoxygenated hemoglobin aggregates and polymerizes in the cytoplasm, creating a semisolid gel that changes the shape and deformability of the cell.

Question 5

When can the sickle cell return to a normal shape?

Answer 5

the sickle cell may return to normal shape with oxygenation in the lungs. However, after repeated episodes of deoxygenation, the cells remain permanently sickled.

Question 6

What if a person has less HbS?

Answer 6

the person with sickle cell trait who has less HbS has little tendency to sickle and is virtually asymptomatic.

Question 7

What inhibits the polymerization of HbS?

Answer 7

HbF inhibits the polymerization of HbS. Therefore, most infants with sickle cell disease do not begin to experience the effects of the sickling until after 8 to 10 weeks of age, when the HbF has been replaced by HbS.

Question 8

There are two major consequences of red blood cell sickling:

Answer 8

chronic hemolytic anemia and blood vessel occlusion. Premature destruction of the cells because of the rigid, nondeformable membrane occurs in the spleen, causing hemolysis and anemia from a decrease in red cell numbers.

Question 9

What does vessel occlusion involve?

Answer 9

vessel occlusion is a complex process involving an interaction among the sickled cells, endothelial cells, leukocytes, platelets, and other plasma proteins.

Question 10

What are the factors associated with sickling and vessel occlusion?

Answer 10

cold
stress
physical exertion
infection
illnesses that cause hypoxia, dehydration, or acidosis.

Question 11

What is the rate of HbS polymerization affected by?

Answer 11

the rate of HbS polymerization is affected by the concentration of hemoglobin in the cell.

Question 12

What does dehydration do?

Answer 12

dehydration increases the hemoglobin concentration and contributes to the polymerization and resulting sickling.

Question 13

What does acidosis do?

Answer 13

acidosis reduces the affinity of hemoglobin for oxygen, resulting in more deoxygenated hemoglobin and increased sickling.

Question 14

Clinical Manifestations: What do people who are homozygous for the HbS gene experience?

Answer 14

severe hemolytic anemia, chronic hyperbilirubinemia, and vaso-occlusive crises.

Question 15

Hyperbilirubinemia:

Answer 15

the hyperbilirubinemia resulting from the breakdown products of hemoglobin often leads to jaundice and the production of pigment stones in the gallbladder.

Question 16

What causes most of the severe complications?

Answer 16

blood vessel occlusion.

-an acute pain episode results from vessel occlusion and hypoxia and can occur suddenly in almost any part of the body. Commonly, obstruction by sickled cells occurs in the abdomen, chest, bones, and joints. Many areas may be affected simultaneously. Infarctions caused by sluggish blood flow may cause chronic damage to the liver, spleen, heart, kidneys, retina, and other organs.

Question 17

When does acute chest syndrome occur?

Answer 17

acute chest syndrome occurs with vessel occlusion in the lungs and is a leading cause of death in people with sickle cell disease.

acute chest syndrome is characterized by sudden chest pain. Cough develops due to pulmonary infiltrates. Respiratory insufficiency results in dyspnea. Painful bone crises may be caused by marrow infarcts.

Question 18

What do children have an increased susceptibility to?

Answer 18

children have an increased susceptibility to osteomyelitis and may experience growth retardation. Transient ischemic attack or cerebral hemorrhage may precede a stroke, and approximately one quarter of people with sickle cell disease develop neurologic complications.

Question 19

What is especially susceptible to damage by HbS?

Answer 19

the spleen.

-because of the spleen’s sluggish blood flow and low oxygen tension, hemoglobin in red cells traversing the spleen becomes deoxygenated, causing ischemia.

Question 20

When does splenic injury begin?

Answer 20

in early childhood, characterized by intense congestion, and is usually asymptomatic. The congestion causes functional asplenia and predisposes the person to life-threatening infections by encapsulated organisms, including Streptococcus pneumoniae, Haemophilus influenzae type b and Klebsiella species. Neonates and small children do not have time to create antibodies to these organisms and rely on the spleen for their removal. In the absence of specific antibody to the polysaccharide capsular antigens of these organisms, splenic activity is essential for removing these organisms when they enter the blood.

Question 21

How is neonatal diagnosis of sickle cell disease made?

Answer 21

on the basis of clinical findings and hemoglobin solubility results, which are confirmed by hemoglobin electrophoresis.

-in the US, screening programs have been implemented to detect newborns with sickle cell disease and other hemoglobinopathies. Cord blood or heel-stick samples are subjected to electrophoresis to separate the HbF from the small amount of HbA and HbS.