Increased strength of erythrocyte aggregates in blood of patients with inflammatory bowel disease.

BACKGROUND: Increased strength of red blood cell (RBC) aggregates are present during the acute inflammatory response and contribute to erythrocyte aggregation and may lead to microvascular dysfunction. Inflammatory bowel diseases (IBDs) are characterized by damage to the bowel wall. This damage may be at least partially attributed to microvascular ischemia caused by enhanced erythrocyte aggregation. The aim of this study was to evaluate the strength of RBC aggregates in the blood of patients with IBD. METHODS: The strengths of RBC aggregates were characterized by integrative RBC aggregation parameters, determined by measuring of RBC aggregation as a function of shear stress. The results are represented as the area under the curve (AUC) of aggregate size plotted against shear stress. For each patient, dynamic aggregation and disaggregation of RBC were recorded and analyzed according to the RBC aggregate size distribution at the different shear stresses. Aggregation indices were correlated with disease activity and inflammatory biomarkers. RESULTS: We examined 53 IBD patients and 63 controls. IBD patients had significantly elevated concentrations of inflammation-sensitive proteins and aggregation parameters. The strength of large aggregates, represented by AUC for large fraction aggregates, among patients (15.2 +/- 18.6) was double that of controls (7 +/- 10.9) (P = 0.006). The strength of large aggregates correlated with disease activity (r = 0.340; P < 0.001) with concentration of fibrinogen (r = 0.575; P < 0.001) and with concentration of high sensitivity C-reactive protein (r = 0.386; P < 0.001). CONCLUSIONS: The strength of RBC aggregates is increased in patients with IBD and correlates with the intensity of the acute phase response. This could contribute to bowel damage in these diseases.

Aggregation of red blood cells in patients with Gaucher disease.

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.

The degree of red blood cell aggregation on peripheral blood glass slides corresponds to inter-erythrocyte cohesive forces in laminar flow.

OBJECTIVE: To determine the degree of correlation between red blood cell (RBC) aggregation on peripheral blood glass slides (PBGS) as determined by image analysis and the inter-erythrocytic cohesive forces as determined in a computerized cell flow properties analyzer (CFA). STUDY DESIGN: RBC aggregation was assessed using both systems simultaneously in healthy volunteers, obese patients and hypercholesterolemic individuals before and following LDL apheresis. RESULTS: A significant (r = 0.5, p < 0.001) correlation was noted between the flow-dependent average aggregate size (AAS) obtained in the CFA and the degree of RBC aggregation on peripheral blood glass slides. Moreover, the enhanced RBC aggregation on the slides was positively associated with the appearance of larger aggregates in the CFA (r = 0.5, p < 0.001) and inversely with the formation of smaller aggregates (r = -0.27, p < 0.04). A similar reduction in RBC aggregation following LDL apheresis was noted in both systems. CONCLUSIONS: The phenomenon of RBC aggregation on peripheral blood glass slides is governed by significant inter-erythrocytic cohesive forces and is not a result of a mere coincidental superimposition of cells. The slide test offers a rapid and simple method of evaluating rheologically significant RBC aggregation, and may allow stratification of patients at risk for atherothrombosis.

A synergistic effect of albumin and fibrinogen on immunoglobulin-induced red blood cell aggregation.

Therapeutic administration of immunoglobulins (Ig) has the potential to precipitate thrombotic events. This phenomenon may be explained by red blood cell (RBC) aggregation, which can be potentiated by Ig. The contribution of plasma albumin and fibrinogen to Ig-induced RBC aggregation is unclear. We examined RBC aggregation in three settings: 1) patients receiving therapeutic infusions of Ig; 2) patients receiving plasma supplemented in vitro with Ig; and 3) patients receiving RBC suspensions in standard buffer with varying concentrations of albumin, Ig, and fibrinogen. Ig infusion augmented aggregation of RBCs from patients with normal or high plasma levels of albumin but decreased aggregation in those with lower plasma albumin concentrations. In vitro, RBC aggregation was significantly increased only when all three components, fibrinogen, albumin, and Ig, were present at or above normal concentrations in the suspension but was unaffected when any one of the components was absent from the suspension. Our results suggest a three-way interaction among fibrinogen, Ig, and albumin that synergistically induces RBC aggregation in plasma. Understanding these interactions may help predict clinically important phenomena related to RBC aggregation, such as thrombotic complications of Ig infusion.