Effects of a Single Sickling Event on the Mechanical Fragility of Sickle Cell Trait Erythrocytes

Abstract

Hemolysis contributes to the pathology associated with sickle cell disease. However, the mechanism of hemolysis or relative contribution of sickling due to hemoglobin polymerization vs. oxidative damage remains unknown. Earlier studies aimed at deciphering the relative importance of these two mechanisms have been complicated by the fact that sickle red cells (SS) have already been affected by multiple rounds of sickling and oxidative damage before they are collected. In our study, we examine the mechanical fragility of sickle cell trait cells, which do not sickle in vivo, but can be made to do so in vitro. Thus, our novel approach explores the effects of sickle hemoglobin polymerization on cells that have never been sickled before. We find that the mechanical fragility of these cells increases dramatically after a single sickling event, suggesting that a substantial amount of hemolysis in vivo probably occurs in polymer-containing cells.

Similar donors—similar blood?

“…RBC MF is gaining acceptance as a useful tool for assessing clinically relevant cell properties, with common approaches using a single value often called a MF index to describe MF properties of RBC units . This study used a multipoint profile, which allowed the calculation of multiple MF‐defining variables from each RBC sample.…”

“…RBC MF is gaining acceptance as a useful tool for assessing clinically relevant cell properties, with common approaches using a single value often called a MF index to describe MF properties of RBC units. 20,27,28 This study used a multipoint profile, which allowed the calculation of multiple MF-defining variables from each RBC sample. These MF variables-reflecting small, medium, and large magnitudes of applied stress-all varied significantly among the donors, even though effort was made to make the RBC units as uniform as possible regarding manufacturing and storage methods as well as donor base.…”

Imaging flow cytometry for automated detection of hypoxia‐induced erythrocyte shape change in sickle cell disease

“…After the incubation, a fixative solution is added and the number of sickled cells is manually counted under a light microscope. In several preclinical and early phase pharmacologic trials in SCD, this assay has been used as an outcome variable to predict clinical effect . Although such a sickling assay is useful, it has several disadvantages: there are questions about its sensitivity and variability and it lacks automated methods to quantitate the percentage of sickled cells from large samples.…”

ACSM and CHAMP Summit on Sickle Cell Trait

“…Although RBCs from persons with SCT can be induced to sickle in vitro (73), the extent to which they sickle in vivo is less elear. The Hb population in RBCs from persons with SCT (assuming minimal Hb F and normal HbA2) exists mostly in three forms: A, S, and a hybrid of a/ß-A and a/ß-S, designated as A/S (74).…”