Investigating red blood cells of sickle cell patients who started therapy.

Sickle cell disease (SCD) is a hemoglobinopathy in which a single nucleotide mutation in the beta-globin chain causes the formation of the abnormal hemoglobin S (HbS). When HbS becomes deoxygenated it polymerises, resulting in sickling of red blood cells (RBCs). These sickled RBCs have strongly reduced deformability, leading to vaso-occlusive crises, multi organ failure and chronic hemolytic anemia.

Hydroxyurea is the only approved drug for the treatment of sickle cell disease. It increases the production of fetal hemoglobin (HbF), thereby lowering HbS levels and, consequently, decreases sickling events. There is however no accurate measurement of a dose-and-effect relation, other than the next life-threatening crisis. There also is no all-inclusive surrogate end-point to estimate disease severity.

Altered red blood cell (RBC) deformability is a feature of many RBC disorders, including SCD. It can be measured using the Lorrca (Laser-assisted Optical Rotational Red Cell Analyzer) under varying circumstances. For instance, the hypoxia-hyperoxia ektacytometry module of the Lorrca enables the measurement of RBC deformability in response to changes in oxygen tension. This is particularly relevant in the field of SCD. Variables known to be of influence for sickling (e.g. HbF levels, presence of transfusion blood) can be studied by using one single fully automated, operator independent test. We hypothesize that this single test can determine an individual’s status and/or susceptibility to sickling, and measure the effect of hydroxyurea therapy.

Red blood cell deformability improves after start of therapy with Hydroxyurea.

baseline, after 1, 3 and 6 months.

Not applicable