Inhibition of polymer-induced red blood cell aggregation by poloxamer 188

Previous reports have suggested that non-ionic poloxamer surfactants of app ropriate molecular mass and composition can reduce red blood cell (RBC) agg regation in whole blood and in RBC-plasma suspensions. We have thus evaluat ed this phenomenon for RBC aggregated by several water-soluble polymers, us ing poloxamer 188 (P188), a non-ionic, tri-block molecule (total molecular mass of 8.40 kDa, 80% polyoxyethylene). Human RBC were washed, then re-susp ended in isotonic solutions of dextran 70 (70.3 kDa), dextran 500 (476 kDa) , PVP (360 kDa) or P-L-GLU (61.2 kDa); density-separated RBC were also stud ied. RBC aggregation was quantitated via a computerized Myrenne Aggregomete r (extent, strength) and by the Microscopic Aggregation Index (MAI) method. Over the range of 0.5 to 5 mg/ml, poloxamer 188 inhibited both the extent and strength of aggregation in a dose-dependent manner, with the magnitude of the decrease related to polymer type (e.g., at 5 mg/ml, 62% decrease for dextran 70 vs. 14% decrease for P-L-GLU); MAI results with dextran 70 also showed a dose-dependent decrease. Poloxamer 188 at 5 mg/ml was more effect ive with younger, less-dense cells. Based upon the depletion model for poly mer-induced aggregation, these findings suggest that poloxamer 188 acts by penetrating the depletion layer near the glycocalyx, thereby reducing the o smotic gradient between the intercellular gap and the suspending medium. Re gardless of the specific mechanism(s) of action, poloxamers appear to offer interesting approaches for future basic science and clinical studies, and thus the possibility for greater insight into RBC aggregation.