Glycoprotein IIB-IIIA inhibitor, monafram decelerate the early phase of red blood cells aggregation

Abstract

It is commonly known that red blood cell (RBC) tendency to reversibly aggregate contribute to the unique flow properties of blood. The fibrinogen-induced aggregation is primarily based on non-specific processes. Nevertheless, recent investigations disclosed a possibility of the specific fibrinogen-RBC binding, however, its role in RBC aggregation remains unclear. We conducted a study to determine whether this specific interaction is essential for natural RBC aggregation. The influence of glycoprotein (GP) IIb-IIIa inhibitor, monafram, on RBC aggregation was compared in RBC suspensions and in whole blood samples from healthy volunteers and, in addition, from patients with systemic lupus erythematosus (SLE) using laser-light backscattering detection and optical tweezers. The effect of monafram on normal RBC aggregation was detectable only in the early phase of intercellular interactions and it involved a deceleration of the aggregation, which was equally expressed in native blood samples and RBC suspensions based on platelet-free plasma. Additionally, in SLE patients, monafram weakened the strength of paired RBC aggregates in platelet-free suspensions. In healthy subjects, strengthened aggregates were found mainly in platelet-containing bulk RBC suspensions. These findings suggest that normal specific fibrinogen-RBC binding could lead to early accelerated formation of RBC aggregates, which could increase possible beneficial effects of reversible RBC aggregation. The strength of RBC aggregates could be modified by platelets in normal subjects and by specific fibrinogen-RBC binding in SLE patients.

Optical tweezers study of red blood cell aggregation and disaggregation in plasma and protein solutions

“…The possibility of fibrinogen binding to RBCs is supported by a number of other studies, as noted in the introduction. 20,23,33,34 Our measurement results of the disaggregation process cannot be explained by the increasing effective interaction area while the linear overlap A between RBCs is decreasing because of the biconcave shape of the cells. RBCs are expected to reach a maximum interaction area at approximately A ¼ 3.5 μm, at which point the effective interaction area is at a maximum, and then should start to decrease.…”

“…Therefore, the RBC interaction mechanism in protein solutions and plasma should be considered still unclear. 20,21,23,33,34 In particular, the RBC disaggregation kinetics obtained using OT appear to require a different interpretation from those predicted by existing interaction models.…”

“…The use of specific fibrinogen-related inhibitors also decreases RBC aggregation. 20,33,34 Therefore, fibrinogen molecules influence RBC aggregation through their specific binding to RBCs. In a number of investigations, an AFM with a fibrinogen-coated tip was used to study fibrinogen interaction with RBCs.…”

Hemorheological properties in patients with type-1 and type-2 diabetes mellitus

“…We divided each of the groups into subgroups in correspondence with the earlier developed criterion [19]: the indices of RBC aggregationand disaggregation being within 95% confidence interval for their normal values, which is a sign of normal aggregation (Nn, n = 19; DM1n, n = 8; DM2n, n = 5), or beyond these limits, which is a sign of "hyperaggregation" (Nh, n = 12; DM1h, n = 11; DM2h, n = 7). The analysis revealed that in the case of normal aggregation-disaggregation dynamics monafram still affected only t 1 , increasing it in all subgroups by 5%-20%.…”

“…These data showed that the specific fibrinogen-RBC binding only slightly accelerated the cell interaction, which could facilitate the appearance of positive consequences of the normally reversible red blood cells aggregation. On the contrary, in the case of "hyperaggregation" (as a rule, transitory in the normal state) the specific interaction of fibrinogen with the RBC membrane could facilitate abnormal phenomena, related to the accelerated formation of cell aggregates having increased stability [11,19].…”