We evaluated the effect of various hydroxyethyl starch (HES) solutions on platelet function. Blood was obtained before and after the IV infusion (10 mL/kg) of saline (n = 10), HES 70/0.5--0.55 (molecular weight in kD/degree of substitution; n = 10), HES 130/0.38--0.45 (n = 10), HES 200/0.6--0.66 (n = 10), or HES 450/0.7--0.8 (n = 10) in otherwise healthy patients scheduled for elective surgery. Collagen and epinephrine were used as agonists for assessment of platelet function analyzer closure times. Flow cytometry was used to assess agonist-induced expression of activated glycoprotein IIb/IIIa complex and P-selectin. Infusion of HES 450/0.7--0.8, HES 200/0.6--0.66, and HES 70/0.5--0.55 prolonged closure times and reduced glycoprotein IIb/IIIa expression, whereas saline and HES 130/0.38--0.45 had no significant effect on platelet variables. P selectin expression was not affected by any solution tested. In vitro experiments demonstrated a less inhibiting effect of HES 130/0.38--0.45 on closure times when compared with other HES solutions. This study shows that HES 450/0.7--0.8, HES 200/0.6--0.66, and HES 70/0.5--0.55 inhibit platelet function by reducing the availability of the functional receptor for fibrinogen on the platelet surface. Our data indicate that fluid resuscitation with HES 130/0.38--0.45 may reduce the risk of bleeding associated with synthetic colloids of higher molecular weight and degree of substitution.

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 degrees 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.

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Parenteral nutrition with standard solutions offers the potential of a relevant cost reduction compared with individualized admixtures in critically ill children.