Thalassemia

The most frequent hematological genetic disorder and one that has a large geographic influence. Clinical signs are a result of hemolysis by chronic anemia. Clinical features include hepatosplenomegaly, bone deformations, and cardiac failure. Strict asepsis is needed.

α-thalassemia, β-thalassemia, and Cooley Anemia (β-thalassemia homozygote).

Most frequently occurring genetic disorder, geographic variability (for example, for α-thalassemia in general population: Congo 60%, Laos 35%, Caribbean 30%, South Europe 10%, France 0.1% of the general population). Other geographical distributions include Asia, Filipino, Mediterranean, Middle Eastern, and, less frequently, India.

Autosomal dominant except for major thalassemia, which is autosomal recessive.

The disease affects synthesis of either α (gene located at 16p13.33 to 16p13.11) or β chain (gene located at 11p15.5) of the hemoglobin.

Hemoglobin synthesis normally provides a just balance between the three different chains α, β, and γ. Thalassemia modifies this status and leads to an abnormal presence of β chain (hemoglobin H) and γ chain (hemoglobin Barts). Hemoglobin (Hb) A is preponderant and so a child with α-thalassemia presents at birth with abnormal HbH and Hb Barts levels. Those allow quantifying of the severity of the thalassemia. Fetal hemoglobin, which disappears within a few months after birth by substitution with HbA, will also be higher. This is a quantitative deficit and clinical expression varies according to deficit. In β-thalassemia HbA2 will be higher than normal but signs will appear after a few months. Certitude diagnosis is obtain by high-performance liquid chromatography (HPLC) of hemoglobin.

Varies with the severity of the disease.

α-thalassemia: Class 1 and class 2 (less than 50% deficit): few signs with anemia; class 3: severe hemolytic anemia with erythroblastopenia, frequent infection, an increased spleen size, and hemosiderosis. Cardiac failure can occur as a consequence of chronic hemolysis. In class 4, generally fetal or neonatal death with anasarca.

β-thalassemia: Other clinical features seen in this disease include major hepatosplenomegaly, growth failure, unconjugated hyperbilirubinemia, and bone marrow hyperplasia that lead to skeletal deformation (frontal bossing, prominent maxilla). Transfusions are frequent with their own complications. Folate deficiency is frequent.

Cooley Sideroblastic Anemia: First described by Thomas Benton Cooley, a Detroit pediatrician-hematologist, who also first described thalassemia in a definitive way. Also known as Thalassemia Major or Homozygous β-Thalassemia. The clinical include severe anemia detected first in childhood, growth retardation, hepatosplenomegaly, and jaundice. Facial and skeletal deformity develop later. Hyperferricemia and abundance of siderocytes in peripheral blood after splenectomy have also been described. Death occurs from hemochromatosis at a relatively young age because of cardiac, hepatic, and endocrine dysfunction.

Evaluate severity of the disease (clinical, history); anemia (clinical, hematocrit, spleen echography); cardiac function (chest radiograph, ECG, echography). Laboratory investigations should include hematocrit, hemoglobin, bilirubin, erythrocyte volume, reticulocyte, HbH.

Strict asepsis is needed during procedures. Difficult direct laryngoscopy can occur as a result of skull malformation. Perioperative cardiac monitoring should be necessary in case of heart failure. Precautions have to be taken during cardioplegia because of the risk of hemolysis at temperature lower than 4°C (39.2°F).

These patients should be considered as immunodeficient for antibioprophylaxis (particularly in the case of a splenectomy). In α-thalassemia, oxidant drugs are contraindicated because they can increase hemolysis (prilocaine, aspirin, vitamin K, sulfonamide, nitroprusside). Other drugs, such as sulprostone and iron, should also be avoided.

ATR-X Syndrome: The acronym ATR-X means alpha-thalassemia, Mental Retardation X-Linked Syndrome. It is characterized by genital abnormalities, microcephaly, midface hypoplasia, severe mental retardation, neuromotor dysfunction, seizures, and hypotonia. Occasionally, the patient might present a ventricular septal defect and gastrointestinal reflux.

Sickle Cell Anemia: Includes a vasoocclusive crisis.