Clinical Guidance

The clinically significant phenotypes of alpha-thalassemia (-thalassemia) are hemoglobin Bart hydrops fetalis (Hb Bart) syndrome and hemoglobin H (HbH) disease. The severity of the -thalassemia syndromes depends on the extent of the alpha globin (-globin) chain defect . Hb Bart syndrome is the most severe clinical condition related to -thalassemia. Affected fetuses are either delivered stillborn at 30-40 weeks' gestation or die soon after birth. The main clinical features are generalized edema and pleural and pericardial effusions as a result of congestive heart failure induced by severe anemia. Notably, red cells with Hb Bart have an extremely high oxygen affinity and are incapable of effective oxygen delivery.

Diagnostic Criteria

Suggestive Findings

Alpha-thalassemia (-thalassemia) has two clinically significant forms: hemoglobin Bart hydrops fetalis (Hb bart) syndrome (deletion/inactivation of all four alpha globin [-globin] alleles;--/--), and hemoglobin H (HbH) disease (most frequently caused by deletion/inactivation of three -globin alleles;--/-) . Hb Bart syndrome should be suspected in the following:

• An at-risk fetus with increased nuchal thickness, thickened placenta, increased cerebral media artery velocity, and increased cardiothoracic ratio on ultrasonography examination at 13-14 weeks' gestation

Management Guidelines

In 2017, the Thalassemia International Federation updated its Guidelines for the Management of Non-Transfusion-Dependent Thalassemia, including beta-thalassemia (-thalassemia) intermedia, HbH disease, and hemoglobin E/-thalassemia .

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with alpha-thalassemia (-thalassemia), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended. Hemoglobin Bart hydrops fetalis (Hb Bart) syndrome. See .

Surveillance Guidelines

HbH disease

• Hematologic evaluation every six to 12 months to determine the steady state levels of Hb

• In children, assessment of growth and development every six to 12 months

• Monitoring of iron load with annual determination of serum ferritin concentration in individuals who have been transfused, in older individuals, and in those given inappropriate iron supplementation. Since serum ferritin may underestimate the degree of iron overload, a periodic noninvasive quantitative measurement of liver iron concentration by MRI is also recommended .