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We evaluated the effects of hydroxyethyl starch with a molecular weight of 200 kD (HES 200 kD) on platelets to gain insight into the potential mechanisms involved in the anticoagulant effects of HES 200 kD. Blood was obtained before and after an IV infusion (10 mL/kg) of either saline (n = 15) or HES 200 kD (n = 15) in otherwise healthy patients scheduled for minor elective surgery. Flow cytometry was used to assess the expression of glycoprotein (GP) IIb-IIIa, GP Ib, and P-selectin on agonist-activated platelets. Overall platelet function was evaluated by assessing thromboelastographic maximum amplitude (MA) in celite-activated blood and platelet function analyzer-closure times by using collagen/adenosine diphosphate cartridges. Saline infusion had no effects on platelet variables, whereas HES 200 kD reduced GP IIb-IIIa expression and MA and prolonged platelet function analyzer-closure times, without affecting the expression of P-selectin and GP Ib. In vitro experiments extended these observations by a concentration-related inhibiting effect of HES 200 kD on GP IIb-IIIa expression. This study demonstrates that cellular abnormalities with decreased availability of platelet GP IIb-IIIa are involved in the anticoagulant effects of HES 200 kD.The present data indicate that an antiplatelet effect of hydroxyethyl starch 200 kD should be considered during plasma volume expansion with this synthetic colloid.