Reply to “Testing for hereditary spherocytosis: a French experience”. Haematologica. 2012;97(12):e48-9

The data presented by Mayeur-Rousse et al.1 in this issue of the journal are very interesting. We stratified the hereditary spherocytosis (HS) patients of our series2 in the 4 categories adopted by the authors finding a perfect correspondence of the results among classes in which a 15-21% and an over 21% decrease in fluorescence was observed; even at a cut-off value of 15%, the test sensitivity is the same (84% vs. 85%), albeit slight differences are observed within the two classes of below 11% and 11-15% (Table 1). Interestingly, the ROC curve analysis performed by Mayeur-Rousse et al. to discriminate HS from healthy controls shows an optimal cut off at 10% decrease in fluorescence, in line with that observed in our series (11%), whereas the comparison of HS with other hemolytic diseases indicated an optimal cut off at 14%. This latter finding raises the important point of differential diagnosis of HS with other rare hemolytic anemias. Applying a cut-off value of 14% to our 84 non-HS hemolytic patients, we were able to discriminate all the hereditary elliptocytosis (HE) from HS but only 4 of 14 congenital dyserythropoietic anemia type II (CDAII) patients, similarly to that found by Mayeur-Rousse et al. However, at this cut off, test sensitivity towards HS decreased from 93% to 84% mainly due to loss of patients with mild/compensated anemia and few spherocytes on peripheral blood smear.3

Table 1.Results of the EMA binding test (at different cut-off categories) in 150 HS patients, 84 non-HS hemolytic anemias and 575 healthy controls (A) compared with the results reported by Mayeur-Rousse (B).

These data further confirm the usefulness of eosin-5-maleimade (EMA) binding as the first screening test for HS, provided that red cell morphology and family history are also taken into account. However, due to the overlap of the ROC curve in HS and hemolytic non-HS patients, we agree that subjects with EMA-binding values between 11-14% deserve further investigation.