Hemoglobin E Disease

At a glance

Hemoglobin (Hb) E is one of the world’s most common and important mutations. The clinical presentation of E β-thalassemia is associated with complications that may lead to serious morbidity and mortality risks. Patients are at high risk for thromboembolism secondary to a hypercoagulable state following resection of the spleen. Hemosiderosis is associated with cardiopulmonary disease such as cardiomyopathy, pulmonary hypertension, and right heart failure. Thromboembolism and hemolysis-induced nitric oxide deficiency result in pulmonary vascular injury and subsequent cardiac disease. Both transfused and nontransfused patients with Hb E β⁰-thalassemia are at risk for life-threatening complications and should be followed by a multidisciplinary team. Other organs that may be involved include endocrine, pulmonary, hepatobiliary, and the skeletal system. The use of hydroxyurea may have some benefit as it is shown to have improved 40% of patients.

Incidence

Most commonly found in Southeast Asia, where the incidence varies from approximately 0 to 0.2% of the population. The frequency of Hb E approaches 60% in many regions of Thailand, Laos, and Cambodia. It is also reported in the Indian subcontinent. It is believed by the WHO that Hb E disease replaced β-thalassemia as the most common thalassemia disorder in many regions, including coastal North America.

Genetic inheritance

Autosomal dominant. Homozygotes have Hb E disease, whereas heterozygotes have Hb E trait.

Pathophysiology

Substitution of glutamic acid at the 26th position of the beta-globin chain where lysine is substituted for glutamic acid. This compound is unstable under oxidative stress.

Diagnosis

Hemoglobin electrophoresis demonstrates approximately 98% hemoglobin E (HbE) and 2% HbF (no HbA) in homozygotes versus approximately 30% (no more than 45%) in heterozygotes (the remaining being normal HbA). Peripheral blood smear reveals numerous target forms (up to 75%) and bone marrow smear usually reveals mild erythroid hyperplasia. Patients with combined HbE/β-thalassemia have predominance of HbE (up to 75%), with increased HbF (7-40%) and variable HbA (1-30%).

Clinical aspects

• Homozygotes (HbE Disease): Marked by microcytosis and hypochromia but usually patients are not anemia. Red blood cells have a normal lifespan. Splenomegaly is absent. The clinical picture is similar to thalassemia trait.

• Hemoglobin E Carriers (HbE Trait): Asymptomatic, although 30 to 35% (no more than 45%) of the hemoglobin is HbE. Peripheral blood smear demonstrates microcytosis without anemia.

• Hemoglobin E and β-Thalassemia (Double Heterozygotes): Affected individuals have significant-to-severe microcytic anemia, increased reticulocyte count and splenomegaly, and usually require chronic transfusion by 6 years of age. Peripheral blood smear reveals the existence of target cells (typical of HbE) and the basophilic stippling typical of β-thalassemia.

Precautions before anesthesia

Check hematocrit. The potential presence of cardiomyopathy (due to hemosiderosis), pulmonary hypertension and right ...