Validation of the Relationship Between Coagulopathy and Localization of Hydroxyethyl Starch on the Vascular Endothelium in a Rat Hemodilution Model

Abstract BackgroundVarious anticoagulant properties have been associated with hydroxyethyl starch (HES), including coagulation disorders measured by point-of-care devices, decreases in von Willebrand factor and coagulation factor VIII, and inhibition of the interactions between platelet-membrane glycoproteins and of coagulation factors by coating of platelets. However, the mechanism for these properties remains unclear. The aim of this study was to test the hypothesis that coagulopathy induced by HES is caused by endothelial or glycocalyx damage as a result of localization of HES on the endothelium, due to the high shear viscosity of blood, using a rat model.MethodsWe compared blood coagulability measured by Sonoclot®, levels of endothelial and glycocalyx damage markers and coagulation factors, and blood shear viscosity when hemodilution was performed with physiological saline (PS), 6% HES 130/0.4 in PS (HES130) and 10% HES 200/0.5 in PS (HES200). To precisely evaluate the basic mechanism of coagulopathy induced by HES, we performed hemodilution with an emphasis on dilutional equality by taking into consideration the intravascular residual rates of the infusion preparations. We also evaluated the localization rates of fluorescently labeled HES on endothelium in the isolated aorta. Statistical analyses were performed by one-way ANOVA followed by Tukey’s test or Kruskal–Wallis test, and then Dunn’s test for multiple comparisons.ResultsSonoclot® measurements revealed that HES130 and HES200 decreased the fibrin gel formation rate to a greater extent than PS, and HES200 decreased the rate more than HES130. Similarly, HES130 and HES200 decreased von Willebrand factor levels to a greater extent than PS. HES130 and HES200 had a more protective effect than PS, with no evidence of damage to the endothelium or glycocalyx. Shear viscosity was variable between all pairs, and was lowest for PS and highest for HES200. HES130 and HES200 demonstrated comparable degrees of localization on the endothelium.ConclusionsHES was shown to cover the endothelium, possibly due to its high shear viscosity, and this mechanism potentially acted to protect the endothelium and glycocalyx. However, this covering effect may be the cause of coagulopathy due to inhibition of von Willebrand factor secretion from the endothelium.