Rheological determinants in patients with Gaucher disease and internal inflammation

Abstract

The purpose of this study was to determine whether the inflammatory response in patients with Gaucher disease (GD) is accompanied by enhanced adhesiveness/aggregation of both red and white blood cells. Sixty patients with GD and matched controls were included. The degree of erythrocyte and leukocyte adhesiveness/aggregation was determined by using a simple slide test and image analysis. Patients with GD had significantly elevated concentrations of fibrinogen (328 vs. 262 mg/dl, P < 0.0001) and accelerated erythrocyte sedimentation rates (27 vs. 13 mm/H, P < 0.005). This was accompanied by a significantly enhanced degree of erythrocyte (75 vs. 85, P < 0.0001) and leukocyte (3.5 vs. 1.3, P < 0.002) adhesiveness/aggregation. The low-grade, smoldering, and subclinical internal inflammation in individuals with GD is accompanied by an increased degree of erythrocyte and leukocyte adhesiveness/aggregation. These findings might have rheological consequences in terms of microcirculatory slow flow and tissue hypoxemia. Am.

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

“…Likewise, the normalization of the dot-plot profile of the two patients subsequently treated with ERT was associated with a normalization of RBC shape observed by SEM. The analysis of RBCs from another Gaucher patient who had (3,12) sometimes in the form of helmet cells (15). Dacryocytes or teardrop cells (8), echinocytes (2), and knizocytes (9,13) were found in most samples.…”

“…Our results using SEM are in line with the latter finding, as we observed RBC aggregates in several untreated patients. 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).…”

“…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).…”

Abnormal properties of red blood cells suggest a role in the pathophysiology of Gaucher disease

“…13,14 However, RBC properties from GD patients have been investigated in a limited number of studies. [15][16][17][18] Among those is a hemorheologic study, which suggested a role for RBCs in the pathophysiology of GD. 16 This study prompted us to further investigate the properties of GD RBCs using multiple techniques, in particular flow adhesion assays.…”