Atlas of pathophysiology, 2 Edition

Part II - Disorders

Hematologic Disorders

Thalassemia

Thalassemia, a group of hereditary hemolytic anemias, is characterized by defective synthesis in the polypeptide chains of the protein component of hemoglobin (Hb). Red blood cell (RBC) synthesis is also impaired.

Thalassemias are most common in people of Mediterranean ancestry (especially Italian and Greek, who develop the form called beta-thalassemia). People whose ancestors originated in Africa, southern China, southeast Asia, and India develop the form called alpha-thalassemia, which reflects deletion of one or more of four Hb genes. Prognosis varies with the number of deleted genes.

In beta-thalassemia, the most common form of this disorder, synthesis of the beta-polypeptide chain is defective. It occurs in three clinical forms: major, intermedia, and minor. The severity of the resulting anemia depends on whether the patient is homozygous or heterozygous for the thalassemic trait. The prognosis varies:

·   thalassemia major—patients seldom survive to adulthood

·   thalassemia intermedia—children develop normally into adulthood; puberty usually delayed

·   thalassemia minor—normal life span.

Causes

Beta-thalassemia

·   Thalassemia major or intermedia—homozygous inheritance of a partially dominant autosomal gene

·   Thalassemia minor—heterozygous inheritance of the same gene

Alpha-thalassemia

·   Deletion of one or more of four genes

Pathophysiology

In beta-thalassemia, total or partial deficiency of beta-polypeptide chain production impairs Hb synthesis and results in continual production of fetal Hb beyond the neonatal period. Normally, immunoglobulin synthesis switches from gamma- to beta-polypeptides at the time of birth. This conversion doesn't happen in thalassemic infants. Their red cells are hypochromic and microcytic. In alpha-thalassemia, a much reduced quantity of alpha-globin chains is produced.

Signs and symptoms

Thalassemia major (also known as Cooley's anemia, Mediterranean disease, and erythroblastic anemia)

·   At birth—no symptoms

·   Infants ages 3 to 6 months—pallor; yellow skin and sclera

·   Infants ages 6 to 12 months—severe anemia, bone abnormalities, failure to thrive, and life-threatening complications

·   Splenomegaly or hepatomegaly, with abdominal enlargement; frequent infections; bleeding tendencies (especially nose bleeds); anorexia

·   Small body, large head (characteristic features); possible mental retardation

·   Facial features similar to Down syndrome in infants, due to thickened bone at the base of the nose from bone marrow hyperactivity

Thalassemia intermedia

·   Some degree of anemia, jaundice, and splenomegaly

·   Signs of hemosiderosis, such as hemoptysis, iron deficiency anemia, or paroxysmal nocturnal hemoglobinemia—due to increased intestinal absorption of iron

Thalassemia minor

·   Usually produces no symptoms

·   Mild anemia, often overlooked

Alpha-thalassemia syndromes (silent carrier, alpha-thalassemia trait, Hb H disease, hydrops fetalis)

·   Reflect the number of gene deletions present

·   Range from asymptomatic to incompatible with life

Diagnostic test results

·   Laboratory analysis reveals low RBC and Hb level, microcytosis, and high reticulocyte count; elevated bilirubin and urinary and fecal urobilinogen levels; and low serum folate level.

·   Peripheral blood smear shows target cells; microcytes; pale, nucleated RBCs; and marked anisocytosis.

·   Skull and long bone X-rays show thinning and widening of the marrow space due to overactive bone marrow, granular appearance of bones of skull and vertebrae, areas of osteoporosis in long bones, and deformed (rectangular or biconvex) phalanges.

·   Quantitative Hb studies reveal significantly increased fetal Hb level and slightly increased Hb A2 level.

Thalassemia intermedia

·   Peripheral blood smear shows hypochromic, microcytic RBCs (less severe than in thalassemia major).

Thalassemia minor

·   Peripheral blood smear shows hypochromic microcytic RBCs.

·   Quantitative Hb studies reveal significantly increased Hb A2 level and moderately increased fetal Hb level.

Treatment

·   Iron supplements contraindicated in all forms of thalassemia

Beta-thalassemia major—essentially supportive

·   Prompt treatment with appropriate antibiotics for infections

·   Folic acid supplements

·   Transfusions of packed RBCs to increase Hb levels (used judiciously to minimize iron overload)

·   Splenectomy and bone marrow transplantation (effectiveness hasn't been confirmed)

Beta-thalassemia intermedia and thalassemia minor

·   No treatment

Alpha-thalassemia

·   Blood transfusions

·   In utero transfusion for hydrops fetalis

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PERIPHERAL BLOOD SMEAR IN THALASSEMIA MAJOR

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