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INTRODUCTION

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Hemoglobinopathies are inherited disorders that result in abnormal hemoglobins. Broadly speaking, the disorders can be classified as disorders of the quantity of hemoglobin such as thalassemia or structural disorders such as sickle cell anemia. Hemoglobinopathies are relatively common and affect 5% to 7% of the world’s population. Sickle cell trait occurs in 8% of African Americans while sickle cell anemia occurs in one of every 600 African Americans. It is estimated that 30 million people worldwide carry at least one copy of the gene for hemoglobin S. Approximately, 1500 children with sickle cell anemia are born annually in the United States.

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Pregnancies complicated by sickle cell anemia are marked by an increase in maternal and fetal complications. The maternal complications relate to the effects of chronic hemolysis, increased susceptibility to infection, intermittent crises, underlying multiorgan involvement, and an increased risk of preeclampsia. There is an increase in maternal mortality. The fetal effects include increased rates of intrauterine growth restriction (IUGR), low birth weight, and preterm birth in addition to the potential for the fetus to be either a homozygote or heterozygote for the sickle cell gene.

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PATHOPHYSIOLOGY

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Hemoglobin is the iron-containing transport protein responsible for oxygen delivery from the lungs to the cells. Adult hemoglobin normally contains 4 globin chains. The most common adult hemoglobin is hemoglobin A1 which consists of 2 α and 2 β chains (α2β2). Adults have a small amount of hemoglobin A2 which consists of 2 chains of α and 2 δ chains (α2δ2). The predominate fetal hemoglobin, hemoglobin F, consists of 2 α and 2 γ chains (α2γ2). After birth, the γ chain is replaced by the β chain. However, hundreds of variations of α, β, γ, and δ chains have been described.

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In sickle cell anemia, there is a point mutation in the β chain in which valine is substituted for glutamic acid. This results in the formation of hemoglobin S which distorts the red cell membrane such that the normal shape and deformability of the red cell are lost. The crescent-shaped red blood cells have a diminished capacity for oxygen transport and their abnormal shape and easy fragmentation causes obstruction to flow, particularly in small vessels. Sickle cells are more adherent to endothelium, further contributing to a viscous cycle of vascular occlusion, thrombosis, and tissue damage. The cells are more easily dehydrated which shortens their life span from the normal 120 days to less than 20. This results in a chronic state of intravascular and extravascular hemolysis.

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The tendency of a red cell to sickle depends upon the amount of hemoglobin S and the level of oxygen. The more the hemoglobin S or the lower the oxygen level, the higher the risk. Patients who are homozygous have 80% to 100% of their hemoglobin in S ...

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