Evaluation of suspected alpha thalassemia minor or alpha thalassemia minima

There are four alpha thalassemia disorders:

• Alpha thalassemia major – Four alpha chains affected. Severe anemia in utero with hydrops fetalis.
• Hb H disease – Three alpha chains affected. Variable severity. Most have symptomatic anemia at birth. Some have pigment gallstones.
• Alpha thalassemia minor – Two alpha chains affected. Also called alpha thalassemia trait. Mild anemia, hypochromia, and microcytosis without other clinically obvious manifestations.
• Alpha thalassemia minima – One alpha chain affected. Also called silent carrier. Most patients are not anemic and do not have microcytosis or Hb H.

If one parent has alpha thalassemia minor with the deletions in cis (aa/- -) and the partner has any alpha thalassemia disorder, the fetus is at risk for Hb H disease or alpha thalassemia major. Hemoglobin Constant Spring (Hb CS) is a non-deletional alpha globin variant relatively common in Southeast Asia and Southern China. Hb CS and other non-deletional variants can be associated with more severe disease than deletional variants. Anemia may be more severe in Hb CS, but the MCV is higher and may be normal. Protein electrophoresis may detect a small Hb CS band, but Hb CS is highly unstable and is often missed with gel electrophoresis; it may be present on HPLC or capillary electrophoresis.

Regions of the world with increased prevalence of alpha globin gene variants include Southeast Asia, China, the Mediterranean region, Middle East, Latin America, and Africa. However, neither race nor ancestry should be used to restrict or determine testing for thalassemia. The American College of Obstetricians and Gynecologists recommends universal hemoglobinopathy screening in individuals planning pregnancy or at the first prenatal visit.^[1]