Hematology · Microcytic Anemia
The facts most likely to be tested
Alpha thalassemia is caused by gene deletions on chromosome 16, leading to decreased production of alpha-globin chains.
The deletion of all four alpha-globin genes results in Hb Bart's (gamma-4 tetramers), causing hydrops fetalis and intrauterine fetal demise.
The deletion of three alpha-globin genes results in HbH disease (beta-4 tetramers), characterized by hemolytic anemia and splenomegaly.
Peripheral blood smears in HbH disease demonstrate target cells and Heinz bodies (precipitated beta-globin chains) visible with supravital stain.
Alpha thalassemia is most prevalent in populations of Southeast Asian and African descent.
Diagnosis of alpha thalassemia is confirmed via hemoglobin electrophoresis or genetic testing for gene deletions.
Alpha thalassemia trait (two-gene deletion) presents as a microcytic, hypochromic anemia with a normal hemoglobin electrophoresis pattern in adults.
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A 28-year-old woman from Vietnam at 24 weeks gestation presents for a routine prenatal visit. Her physical exam is unremarkable, but laboratory studies reveal a microcytic anemia with a hemoglobin of 10.2 g/dL and a mean corpuscular volume (MCV) of 72 fL. Her hemoglobin electrophoresis shows normal levels of HbA, HbA2, and HbF. Her iron studies are within normal limits, and she has no history of blood loss.
What is the most likely diagnosis?
Alpha thalassemia trait (silent carrier or two-gene deletion)
The patient presents with microcytic anemia and normal iron studies, which is classic for thalassemia; the normal hemoglobin electrophoresis in an adult is the hallmark finding for alpha thalassemia trait.
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Etiology / Epidemiology
Genetic deletion of alpha-globin chains common in Southeast Asian and African populations.
Clinical Manifestations
Microcytic anemia with target cells; severe cases present with hydrops fetalis.
Diagnosis
Diagnosis confirmed via hemoglobin electrophoresis; genetic testing identifies gene deletions.
Treatment
Mild cases require no treatment; severe cases require chronic blood transfusions and iron chelation.
Prognosis
Risk of iron overload; monitor serum ferritin and cardiac function.
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Epidemiology & Etiology
Caused by decreased synthesis of alpha-globin chains due to gene deletions on chromosome 16. Highly prevalent in Southeast Asian, Chinese, and African populations. Inheritance follows an autosomal recessive pattern.
Pertinent Anatomy
Humans possess four alpha-globin genes. The clinical severity is directly proportional to the number of deleted genes (1 to 4).
Pathophysiology
Reduced alpha-globin leads to an excess of beta-globin chains, forming unstable Heinz bodies. These precipitates damage the RBC membrane, leading to hemolysis and ineffective erythropoiesis. In the absence of alpha-globin, gamma-tetramers (Hb Barts) or beta-tetramers (Hb H) form, which have high oxygen affinity and poor tissue delivery.
Clinical Manifestations
Silent carriers (1 gene) are asymptomatic. HbH disease (3 genes) presents with hemolytic anemia, splenomegaly, and target cells on smear. Hydrops fetalis (4 genes) is incompatible with life, resulting in fetal death due to severe hypoxia and high-output heart failure.
Diagnosis
The gold standard is hemoglobin electrophoresis, though it may be normal in silent carriers. Peripheral smear shows microcytic, hypochromic anemia with target cells. Genetic testing is the definitive method to quantify gene deletions.
Treatment
Asymptomatic patients require no intervention. Patients with HbH disease should avoid oxidative drugs (e.g., sulfonamides) that trigger hemolysis. Severe cases require chronic blood transfusions and deferoxamine for iron chelation to prevent hemochromatosis.
Prognosis
Patients with chronic hemolysis are at high risk for iron overload. Regular monitoring of serum ferritin and cardiac function is mandatory to prevent end-organ damage.
Differential Diagnosis
Iron Deficiency Anemia: low ferritin, high TIBC
Beta Thalassemia Trait: elevated HbA2
Sideroblastic Anemia: ringed sideroblasts on bone marrow biopsy
Anemia of Chronic Disease: normal/high ferritin
Lead Poisoning: basophilic stippling