Binding of Hydroxyethyl Starch Molecules to the Platelet Surface

In Brief Hydroxyethyl starch (HES) solutions impair platelet function by reducing the availability of the fibrinogen receptor. This effect is not mediated by intracellular signal transduction pathways. Also, an unspecific coating of platelets by HES macromolecules may be responsible for its antiplatelet effects. To test this hypothesis, we investigated the binding of fluorochrome-coupled HES to the surface of human platelets using whole blood flow cytometry. Citrated whole blood from 8 volunteers was incubated (5 min, 22°C, in the dark) with fluorescein isothiocyanate (FITC)-coupled HES (200-kDa molecular weight, 0.5 degree of substitution, 0.042 molar ratio of FITC-conjugation) resulting in 0%, 1%, 3%, 5%, 10%, 20%, and 40% hemodilution. The percentage of platelets binding FITC-HES was determined using a FACSCalibur™ flow cytometer and CellQuestPro™ software. The percentage of FITC-positive platelets increased in a concentration-dependent manner reaching statistical significance at 10% hemodilution. Binding was independent of fibrinogen receptor blockade. The present experiments clearly demonstrate that extracellular binding of HES to the platelet surface is, at least in part, responsible for the antiplatelet effects of HES by blocking the access of ligands to the platelet fibrinogen receptor. IMPLICATIONS: Hydroxyethyl starch solutions are widely used for fluid replacement in patients undergoing surgery but may compromise blood coagulation. The present study demonstrates that one of the mechanisms for this unwanted side effect is related to the binding of hydroxyethyl starch to the outer surface of blood platelets.