Rare hemoglobin variants: our experience with Sysmex hematology analyzers

The consolidation of laboratory activities optimizes resources and improves the expertise of the staff that encounters more frequently rare and exceptional cases. In the recent months, the Romagna Greater Area Laboratory, which provides a diagnostic service for over a million inhabitants in North Italy, detected an unusual instrumental alarm in a few routine blood counts. Further investigations demonstrated the presence in the samples of hemoglobin (Hb) variants, characterized with subsequent molecular analysis as Hb Leiden and Hb G-Ferrara. These Hb variants reduce the fluorescence signal hampering the differential leukocyte count carried out by the Sysmex XE2100 hematology analyzer. In all the investigated cases, irregular contracted red blood cells (RBC) and target RBC were present. HPLC analysis of the two Hb variants shows Hb Leiden and Hb G-Ferrara peaks at 4.28 min and 3.23 min of elution time, respectively. It is clinically important to identify carriers of these variants in specific clinical setting, since heterozygotes for these Hb variants are asymptomatic, but complications could be induced by drug therapies, viral infection or heterozygosity for beta-thalassemia or other Hb variants. Our findings demonstrate the importance to investigate samples with low fluorescence when assayed using Sysmex analyzers. Finally, the reported cases confirm the effectiveness of tight integration between huge routine workload and specialized competence for the detection of unusual clinical conditions.