In the latest Case Record of the Massachusetts General Hospital, a 62-year-old woman presented with dyspnea, anemia, and paraspinal masses. Examination revealed splenomegaly. Laboratory studies revealed microcytic anemia. A diagnostic test result was received.
A common feature of all thalassemias is that clinical symptoms arise less from the deficit in hemoglobin production than from the accumulation of the unpaired globin chain produced in normal amounts by the other globin genes. These chains remain unpaired because of the deficit in synthesis of the affected chain and therefore are highly unstable. They cause the precipitation of inclusion bodies that damage the mitochondrial, nuclear, and plasma membranes of developing erythroblasts, and they provoke apoptosis that results in the premature death of most developing erythroid precursors.
• What are the causes of microcytosis?
Microcytic anemias are due to defects in hemoglobin biosynthesis resulting from reduced supply of iron (iron deficiency), inadequate delivery of iron (anemia of chronic inflammation), impaired production of heme (sideroblastic anemia), or defective synthesis of the globin component of hemoglobin (thalassemia).
• How can thalassemia be differentiated from other causes of microcytosis?
An extremely low mean corpuscular volume effectively eliminates the possibility of anemia of chronic inflammation and sideroblastic anemia; in adults, these anemias almost never present with a mean corpuscular volume below 70 fl. Moreover, the mean corpuscular volume in iron deficiency rarely falls below 80 fl until the hematocrit is well below 30 and the red-cell count is less than 4 million. In contrast, a hallmark of thalassemia is a mean corpuscular volume that is disproportionately low for the degree of anemia.
Morning Report Questions
Q: What are the causes of thalassemia intermedia?
A: Thalassemia intermedia can occur by several mechanisms including coinheritance of a mild (beta)-thalassemia allele and a more severe (beta)-thalassemia allele, hemoglobin H (HbH) disease (a moderately severe form of (alpha)-thalassemia that is compatible with survival to adulthood), and in Southeast Asia, a common and distinctive hemoglobinopathy called hemoglobin E/(beta)-thalassemia, due to coinheritance of a (beta)-thalassemia allele and the allele for (beta)Î•-globin.
Q: What is hemoglobin H (HbH) disease?
A: HbH disease, or (alpha)-thalassemia intermedia, results from inactivation of three of four (alpha)-globin genes; located on the short arm of chromosome 16 is a pair of each of these inactivated genes. Decreased production of (alpha)-globin chains results in a relative excess of (beta)-globin chains, which form unstable (beta)4 homotetramers known as HbH. HbH precipitates in developing erythrocytes in the bone marrow, leading to ineffective erythropoiesis.