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.

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SAMOCHA-BONET, DORIT, DOV LICHTENBERG, AARON TOMER, VARDA DEUTSCH, TAMAR MARDI, YELENA GOLDIN, SUBCHI ABU-ABEID, GALINA SHENKERMAN, HANA PATSHORNIK, ITZHAK SHAPIRA, AND SHLOMO BERLINER. Enhanced erythrocyte adhesiveness/aggregation in obesity corresponds to low-grade inflammation. Obes Res. 2003;11: 403-407. Objective: Previous studies have suggested that obesity enhances the inflammatory response, producing macromolecules involved in the induction and/or maintenance of increased erythrocyte aggregation. The objectives of this study were to evaluate the correlation between inflammation markers, erythrocyte adhesiveness/aggregation, and the degree of obesity and to assess phosphatidylserine expression on erythrocyte surface membrane of obese vs. nonobese individuals. Research Methods and Procedures: Erythrocyte adhesiveness/aggregation in the peripheral venous blood was evaluated by using a new biomarker, phosphatidylserine expression was assessed by means of flow cytometry, and markers of inflammation were measured in 65 subjects: 30 obese [body mass index (BMI) ϭ 41 Ϯ 7.7 kg/m 2 ] and 35 nonobese (BMI ϭ 24 Ϯ 2.7 kg/m 2 ) individuals. Pearson correlations and Student's t test were performed. Results: A highly significant difference was noted in the degree of erythrocyte adhesiveness/aggregation and markers of inflammation between the study groups. BMI correlated with erythrocyte adhesiveness/aggregation (r ϭ 0.42, p ϭ 0.001), erythrocyte sedimentation rate (r ϭ 0.42, p ϭ 0.001), high-sensitive C-reactive protein (r ϭ 0.55, p Ͻ 10 Ϫ4 ), fibrinogen (r ϭ 0.37, p ϭ 0.004), and white blood cell count (r ϭ 0.45, p Ͻ 10 Ϫ4 ). The degree of erythrocyte adhesiveness/aggregation correlated with erythrocyte sedimentation rate (r ϭ 0.5, p Ͻ 10 Ϫ4 ), high-sensitive C-reactive protein (r ϭ 0.56, p Ͻ 10 Ϫ4 ), fibrinogen (r ϭ 0.54, p Ͻ 10 Ϫ4 ), and white blood cell count (r ϭ 0.32, p ϭ 0.01). Discussion: Our results suggest that obesity-related erythrocyte adhesiveness/aggregation is probably mediated through increased concentrations of adhesive macromolecules in the circulation and not necessarily through hyperlipidemia or phosphatidylserine exposure on erythrocyte's membrane.

Recent studies have shown that C-reactive proteins have a pathogenetic role in atherothrombosis and concentrations of these substances could be used as a marker for future vascular events. The objective of this study was to determine gender differences in highly sensitive C-reactive protein (hs-CRP) in individuals with atherothrombotic risk factors and apparently healthy ones. We have presently matched 469 females and 469 males having the same age and body mass index (BMI). Of these, 210 men and 210 women had no atherothrombotic risk factors. In this group the hs-CRP concentrations were 1.6+/-3.4 mg l(-1) in women and 1.0+/-2.7 mg l(-1) in men (p<0.0005). These values were 2.1+/-3.4 mg l(-1) and 1.5+/-2.8 mg l(-1), respectively, in the entire cohort (p<0.0005), which included also individuals with atherothrombotic risk factors. We conclude that significant gender differences exist in hs-CRP concentrations despite perfect matching for age and BMI. These differences should be reflected in guidelines that suggest hs-CRP cut-off points for the stratification of vascular risk.