Aggregation of red blood cells in patients with Gaucher disease

Abstract

Summary Gaucher disease is associated with increased red blood cell (RBC) aggregation, but the pathophysiological significance of this phenomenon and its correlation with disease manifestations are unclear. RBC aggregation was evaluated in 43 patients with Gaucher disease and 53 healthy controls. Dynamic RBC aggregation was examined in a narrow‐gap flow chamber at varying shear stress. Compared with the controls, RBC aggregation in Gaucher disease was increased by 25%. Comparison of RBC aggregation in autologous plasma and in dextran (500 kDa) showed an increase both in plasma‐dependent (extrinsic) and ‐independent (intrinsic) RBC aggregation. Subgroup analysis revealed that increased RBC aggregation was limited to patients with an intact spleen. RBC aggregation in patients did not correlate with plasma fibrinogen concentration, disease severity, enzyme replacement therapy or genotype. We conclude that RBC aggregation is increased in patients with Gaucher disease and an intact spleen, possibly reflecting the accumulation of glucocerebroside and other substances in the plasma and RBC membranes of these patients. Our results do not support a role for RBC aggregation in the pathogenesis of vascular complications of Gaucher disease.

A cytometric study of the red blood cells in Gaucher disease reveals their abnormal shape that may be involved in increased erythrophagocytosis

“…Increased blood viscosity in GD may be related to a low-grade inflammatory state slowing down microcirculation flow and limiting oxygen supply to surrounding tissues (15,43). Inflammatory markers may not, however, fully account for the enhanced aggregation of Gaucher RBCs (16,44). Whereas this enhanced aggregation does not appear to be correlated with the occurrence of microvascular infarcts (44), the conjunction of enhanced aggregation, reduced deformability, and putative limited oxygen supply may together contribute towards the observed avascular necrosis in GD.…”

“…On the other hand, the enhanced erythrophagocytosis observed in patients with GD clearly illustrates the abnormal qualitative macrophage-RBC interactions occurring in this disease (3)(4)(5), however the respective involvement of each cellular type remains unclear. The involvement of Gaucher RBCs is suggested by their abnormal rheological properties (14)(15)(16) and their ability to store GlcCer (13), the consequences of which are not known.…”

“…Any change in the RBCs in GD which would also alter the crosstalk with macrophages has not however been described. The RBCs in GD are known to accumulate GlcCer (13), have a reduced deformability (14) and be prone to aggregate (15,16). Furthermore, whilst the shape of RBCs was not considered abnormal in a series of patients with the neurological Norrbottnian form of GD, an excess of targeted cells was observed in splenectomized patients (17).…”

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

“…These patients have altered humoral and cellular immune profiles, including altered NKT cell numbers and function. Data from GD suggest an effect of GC on the cell membrane; hence, some patients have increased red blood cell aggregation due to changes in the properties of the cell membrane (1,2,89). Studies of these patients has implied that GC is involved in NKT cell regulation (90,105,109).…”

“…These molecules have effect in signal transduction and in the pathogenesis of several diseases (1,2,76,80,92,96). Cer is the simplest molecule in this family, and it serves as a precursor for the synthesis of the three main types of complex SLs (SMs, GSLs, and gangliosides), respectively.…”