H e m o g l o b i n o p a t h i e s
Hemoglobinopathies
• Group of inherited disorders in which structurally abnormal hemoglobin is
made. Some of these abnormal hemoglobins function like normal
hemoglobin, but some have abnormalities that lead to hemolysis.
• Hgb S (which produces the disease called sickle-cell anemia) is the most
common abnormal hemoglobin.
Pathogenesis of Sickle-Cell Anemia
• Point mutation in a beta chain gene leads to substitution of valine for
glutamate.
• Resultant abnormal hemoglobin, Hgb S, has abnormal physical and
chemical properties:
• On deoxygenation, Hgb S molecules aggregate and polymerize.
• Red cell shape is distorted into sickle shape.
• After many episodes, red cell becomes permanently sickle-shaped.
• Results:
• Chronic hemolytic anemia (sickle cells not as deformable as normal
biconcave disks).
• Occlusion of small blood vessels leading to ischemic tissue damage.
Clinical Features of Sickle-Cell Anemia
• Occurs predominantly in blacks. Eight percent of blacks in US are
heterozygous; one black child in 600 is homozygous.
• Patients who are heterozygous rarely have significant clinical or hematologic
manifestations.
• Severity of disease is very variable, for unknown reasons.
• Increased susceptibility to infection (after autosplenectomy, encapsulated
organisms like Streptococcus pneumoniae and Hemophilus influenzae pose
big risk).
• Chronic hemolysis (Hgb=6-10).
• Vaso-occlusive disease
• Usually occurs as an acute crisis, precipitated by infection, hypoxia, or
unidentified causes.
• Children: pain in hands, feet often first symptom.
All ages: pain common in bones, lungs, abdomen.
• Spleen may undergo massive enlargement (due to red cell sequestration)
in early childhood; by early adulthood, spleen is reduced to small, fibrotic
remnant (due to recurrent hemorrhage, infection).
Morphology of Sickle-Cell Anemia
• Sickle cells.
• After autosplenectomy occurs, see a "post-splenectomy blood picture":
• nucleated red blood cells
• targets
• Howell-Jolly bodies
• Pappenheimer bodies
• slightly increased platelet count.
Treatment of Sickle-Cell Anemia
• Prevent triggers: infection, fever, dehydration, hypoxemia.
• Take extra precautions to prevent infections due to encapsulated bugs
(vaccinate, give prophylactic antibiotics).
• Blood transfusions during severe crises (or routinely, in certain patients).
• Bone marrow transplantation.
