Effects of hydroxyethyl starches on hemostasis

Abstract

Introduction: Structural characteristics of hydroxyethyl starch (HES) molecules have been shown to modulate their influence on blood coagulation (1). HES with a medium molecular weight of 200 kD has been found to compromise platelet contribution to hemostasis (2). The aim of this study was to evaluate the effects of HES solutions of varying molecular weight on platelet reactivity. Methods: Following IRB approval and informed consent, 40 patients ASA 1-2 were randomly assigned to receive 10 ml/kg of either saline, HES 130 kD, 200 kD, or 450 kD infused intravenously over 30 min. Citrated whole blood samples were obtained before and after infusion. Flow cytometry was used to assess the expression of platelet fibrinogen receptor (GP IIb-IIIa) in response to adenosine diphosphate using the monoclonal antibody PAC-1. Thrombelastographic maximum amplitude (MA) was determined in celite activated blood after recalcification. Collagen/epinephrine were used as agonists for assessment of closure times with the Platelet Function Analyzer (PFA). Statistics: analysis of variance (P<0.05). Results: HES 450 kD and HES 200 kD significantly decreased MA (by 23% and 22%, respectively), prolonged closure times (by 51% and 24%, respectively), and reduced PAC-1 binding to platelets (by 26% and 23%, respectively). HES 130 kD and saline had no significant effects on the parameters investigated. The differences between HES 130 kD and HES 450 kD, and between HES 130 kD and HES 200 kD were statistically significant. Conclusion: These results show that HES 200 kD and HES 450 kD inhibit platelet function by reducing the availability of the functional receptor for fibrinogen on the platelet surface. In contrast, HES 130 kD had no significant anti-platelet effect and the contribution of platelets to clot strength was maintained. These data indicate that fluid resuscitation with HES 130 kD may reduce the risk of bleeding associated with synthetic colloids of high molecular weight.