HS.(A)Ektacytometry of blood samples from the patient before and after splenectomy and from his parents. The patient had AR HS due to compound heterozygosity of SPTA1 c.4295del (p.L1432*), shared with the mom, and SPTA1 c.4339-99C>T, shared with the dad. The dad and the proband were also found to carry the PIEZO1 VUCS c.6205G>A (p.Val2069Met). The parents had a normal ektacytometry with no evidence of xerocytosis for the father, offering reassurance that the PIEZO1 VUCS is benign, while the patient after splenectomy had a typical HS curve. Before splenectomy, the patient was chronically transfused. Ektacytometry at that time was performed at a nadir before the next transfusion and 2 months after a previous one. Transfused RBCs have obviously modified the curve, giving a falsely normal Omin (ie, the hypotonic osmolality where the elongation index is minimal). The value of Omin provides information on the initial surface-to-volume ratio of the cell sample. A shift to the right reflects a decrease in the surface area/volume ratio and corresponds to increased osmotic fragility. (B) Blood smear of the patient about 18 months post partial splenectomy before starting to require transfusions again, demonstrating significant anisopoikilocytosis and polychromasia as well as many spherocytes, typical for AR SPTA1-associated HS. (C) Blood smear of the patient 5 years after total splenectomy, stable and without need of transfusions since the time of that surgery. Moderate anisopoikilocytosis and several spherocytes are still noted. Scale bar = 14 mm. Details on the ektacytometry assay and parameters can be found at https://www.cincinnatichildrens.org/service/c/cancer-blood/hcp/clinical-laboratories/erythrocyte-diagnostic-lab/ektacytometry.