Analysis of annual distributions of hemoglobin A2 values as a method to test for HbA2 standardization.

BACKGROUND AND AIMS: The monitoring of yearly distributions of HbA2 measured has been indicated as a reliable indicator of worldwide standardization. MATERIALS AND METHODS: Measurements/year of HbA2 have been collected over three consecutive years in 15 Italian laboratories each using the same analytical method over three years period. HbA2 distributions, cleaned of replicated measurements, were compared by the overlapping area of the raw probability density functions expressed by coefficient eta (η), and by comparing the reference intervals for the central part of each distribution estimated by the indirect method refineR using the R package "refineR". RESULTS: According to the overlapping areas analysis the distributions/year of the data provided by 4 centers able to perform at least 1000 measurements/year were similar in 2 consecutive years. Moreover, the reference intervals provided by 2 centers using the same analytical methods in two separate locations over the three consecutive years, were very similar. The highest overlap (99.7 %) was observed in one center over two consecutive years. The overlapping areas were very high (93.6-95.7%) in 8 out of 9 inter-comparisons. CONCLUSION: Despite the limitations of this study the yearly distribution of the HbA2 measured in various centers appears a reliable tool to test HbA2 standardization over different centers using different analytical methods.

A Novel εγδß-Thalassemia Deletion Associated with Severe Anemia at Birth and a ß-Thalassemia Intermedia Phenotype Later in Life in Three Generations of a Greek Family.

We describe a novel deletion causing heterozygous εγδß-thalassemia (εγδß-thal) across three generations of a Greek family. The Greek deletion is about 72 kb in length, spanning from the hypersensitive site 4 (HS4) in the locus control region (LCR) to the 3' end of the ß-globin gene, thus encompassing the entire ß-globin gene cluster. The deletion caused severe but transient neonatal anemia and a non transfusion-dependent chronic hemolytic anemia state later in life, resembling mild ß-thalassemia intermedia (ß-TI) rather than ß-thalassemia (ß-thal) trait, as had been previously reported. Apart from the presentation of clinical and laboratory characteristics, the challenges involving clinical management are also discussed.