In response to the letter of Burkhardt et al. (1), we concur with the authors of the letter that multi-angle light scatter can be used to establish the size and hemoglobin concentration of red blood cells (RBCs) that are isovolumetrically sphered in an appropriately formulated isotonic reagent (normal discoidal RBCs are sphered in such reagent). It is also clearly evident that knowledge of the cell size and hemoglobin content of RBCs is valuable in pointing towards RBC abnormalities. The key novelties illustrated by our work is the observations that in a carefully selected three dimensional (3D) space, the scatter signals from the 3 angular intervals of RBCs which were not sphered in the reagent did not fall close to the pre-calibrated grid of the 3D surface conserved to sphered RBCs. The abbreviation which was specifically used to refer to abnormally-shaped RBCs was AbnRBC as defined in the article Abstract on page 43. The term “AbnRBC” was not intended to refer to RBC abnormalities for cell size or hemoglobin concentration, as pointed out again on page 51 under Table 5 (note a) of our article. Thus, it was with specific reference to RBCs which were not sphered in both RBC reagents that we made our observations. In their letter, Burkhardt et al. (1) also suggest that our paper implies a discrete separation of sphered and non-sphered RBCs by the 3D method. This was not our intention and on review of our manuscript, it is difficult to understand why the authors of the letter feel that this is implied. In a situation analogous to cell volume and cell hemoglobin concentration, abnormalities in cellular shape are commonly a continuum of spectrum of magnitude rather than being compartmentalized populations. We have on hand, numerous instances in which samples containing AbnRBCs show cytometric events falling more distant from the calibrated 3D surface than is the case in normal bloods. In Figure 3 of our article, we show an example of a normal sample and a sample containing AbnRBCs. As clearly shown in Fig 3d, it was never suggested that AbnRBCs form a discrete cluster. For the proposed method to be of value, boundaries of abnormality have to be established which give reference ranges for normal RBCs. Six samples in Table 5 of our article contained AbnRBCs as shown and the results analyzed by the closest point finding software of the 3D method was compared to the blood smear results. Fairly good correlation was obtained between the two methods. Concerning schistocytes, at the time of writing the article, we were unaware of any 510(k) cleared reportable parameters pertaining to schistocyte counting derived from any of the Bayer systems. If the situation has been changed since and Bayer hematology instruments now can count and report schistocytes, thank you for informing us. On the last comment in the Letter, the authors refer to the CHr parameter as a “Gold Standard” for iron-deficiency state. To assert that the CHr is the gold standard, implying it being a reference method, is not only not supported in the literature, but is not indicated as such by any publication we can find by a recognized international laboratory standards group, such as ICSH or NCCLS. Therefore, we said that we planned to investigate this area further because the diagnostic threshold for iron deficiency seems to vary with the patient population (2, 3) and may not be reliable in individuals with elevated red cell MCV values (4) (Blood). The finding of alterations in the CHr in healthy individuals following extreme exercise also raises questions as to the specificity of the measurement (5). Perhaps, the claim of red cell parameters serving as a gold standard will require the combination of several measurements, such as both the CHr and the reticulocyte IRF (RNA content) (6). The term, anemia of chronic diseases, was used in our article to describe a broad spectrum of anemias associated with chronic disease state.