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R. Huisjes et al.
used a capillary-based method with determination of the hematocrit to measure MCHC. In line with previous observations,36–38 we found that automated measurements of MCHC of pathological RBC are imprecise for HS patients (see Online Supplementary Figure S5). Inaccuracy of automated MCHC detection of dehydrated RBC has been discussed for over 30 years.36 It results from a substantial overestimation of MCV, both values being reliant on hematocrit detection or calculation methods.39,40 As men- tioned previously, others have shown that increased hemoglobin concentrations correlate with milder disease severity scores in HS.9,11 We show that MCHC, calculated based on the capillary hematocrit, correlated with blood hemoglobin content (Figures 1G, 3A, and 4D).
Conclusions
This study reveals the factors defining RBC longevity and erythropoietic activity in patients with HS. These fac- tors include membrane stability, which in turn depends on the localization of mutations affecting vertical or horizon- tal interactions within the membrane cytoskeleton and on the presence of splenic filtering capacity. Mild HS is asso-
ciated with prolonged survival of RBC in the circulation, allowing greater loss of membrane, which results in small- er and denser RBC. Shorter-lived, unstable RBC from patients with severe HS phenotype are more heteroge- neous and less dense, as reflected by lower MCHC.
Parameters that specifically mark clinical severity in HS are summarized in Table 2 and are RBC density (MCHC, Percoll, Ohyper), RBC deformability (EImax), and RBC hetero- geneity (RDW). These parameters may be used to monitor the success of supportive therapy and assist in the develop- ment of new personalized treatment regimens.
Funding
Funding for the research leading to these results was received from the European Seventh Framework Program under grant agreement number 602121 (CoMMiTMenT) and from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement number 675115 — RELE- VANCE — H2020-MSCA-ITN-2015/H2020-MSCA-ITN- 2015. This work was generated within the European Reference Network on Rare Hematological Diseases (ERN- EuroBloodNet) – FPA No. 739541
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