Binding of Hydroxyethyl Starch Molecules to the Platelet Surface

Abstract

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.

Effects of Acute Hypervolemic Fluid Infusion of Hydroxyethyl Starch and Gelatin on Hemostasis and Possible Mechanisms

“…Furthermore, vWF-mediated rolling and adhesion of platelets to subendothelial collagen could be diminished by the reduction in VIII/vWF complexes. 13 On the other hand, HES may also induce cellular abnormalities with a decreased agonistinduced expression and activation of platelet surface GPIIb-IIIa by blocking the access of ligands to surface receptors or by an unspecific modification of cytoplasmic membrane structure and a consecutive Effects of AHFI of HES and GEL on Hemostasis / Jin, Yu 5 inhibition of the conformational change of GPIIbIIIa, [14][15][16] which impairs platelet adhesion to surfacebound fibrinogen and, most importantly, soluble fibrinogen ligand binding between neighboring platelets, causing platelet aggregation. By adhesion and aggregation, platelets form a maze in which plasma can clot without the thrombin being washed away.…”

Effects of Synthetic Versus Natural Colloid Resuscitation on Inducing Dilutional Coagulopathy and Increasing Hemorrhage in Rabbits

“…53 The inhibition of platelet function is caused by a decrease in expression or blocking of platelet fibrinogen receptor glycoprotein IIb-IIIa. 54,55 In addition to these effects, the oncotic force of synthetic or natural colloids also have a significant influence on coagulation. Infusion of colloids causes efflux of plasma proteins from blood to interstitial space that is driven by the oncotic forces.…”

Cardiovascular, Colloid Osmotic Pressure, and Hemostatic Effects of 2 Formulations of Hydroxyethyl Starch in Healthy Horses

“…The effects on hemostasis are related to both dilution of and interference with coagulation factors, fibrinolysis, and platelets 5, 6. HES molecules might adhere to platelet membranes, and they might impair fibrinogen binding by direct effects on the GPIIb/IIIa fibrinogen receptor, or by preventing association of the receptor and ligand 7. Effects are dose dependent and limit the maximum recommended dose of these products 5.…”