HPLC: high performance liquid chromatography; CBC: complete blood count; Hb: hemoglobin; MCV: mean corpuscular volume; MCH: mean corpuscular hemoglobin.
* Whether screening for hemoglobinopathy should be performed routinely or targeted to populations at increased risk is controversial. Given the increasingly diverse ethnic and geographic distribution of hemoglobinopathy genotypes in the United States and elsewhere, risk assessment based on race and ethnic origin alone may not be reliable.
¶ If MCV <80 fL and/or MCH <27 pg, iron deficiency must be excluded (eg, ferritin level) because it can mask beta-thalassemia trait. The diagnosis heterozygous beta-thalassemia is based on an increased HbA2 level; individuals with beta-thalassemia and concomitant iron deficiency can have a normal rather than increased HbA2 level.
Δ If other hemoglobin variants are detected, consult a hematologist.
◊ CBC and hemoglobin analysis will not identify alpha thalassemia minima (ie, silent carrier with loss of one of the four alpha globin genes), which can only be identified by DNA analysis. If the mother is a silent carrier and the father has cis alpha thalassemia trait (loss of two alpha globin genes on the same chromosome), or vice versa, their child has a one in four chance of HbH disease (ie, loss of three of the four alpha globin genes). Fetuses with HbH disease have hemolytic anemia and are symptomatic at birth, often presenting with neonatal jaundice and anemia, and occasionally with hydrops fetalis. Most affected individuals do not require chronic transfusion support during the first decade of life, but splenectomy or transfusion support during the second or third decade of life is often necessary. Iron overload due to increased iron absorption is also a significant issue.