BJA Advance Access originally published online on February 7, 2006
British Journal of Anaesthesia 2006 96(4):455-463; doi:10.1093/bja/ael019
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Molar substitution and C2/C6 ratio of hydroxyethyl starch: influence on blood coagulation
1Department of Anaesthesiology, University Hospital Lausanne Lausanne, Switzerland
2Department of Anaesthesiology, B. Braun Melsungen AG Melsungen, Germany
3Pharmaceutical Development, B. Braun Medical SA Crissier, Switzerland
4Coagulation Laboratory, Division of Haematology, University Hospital of Zürich Zurich, Switzerland
*Corresponding author. E-mail: donat.spahn{at}chuv.ch
Background. Development of hydroxyethyl starches (HES) with a low impact on blood coagulation but a long intravascular persistence is of clinical interest. A previous in vitro study showed that low substituted high molecular weight HES does not compromise blood coagulation more than medium molecular weight HES. In the present study we assessed the individual effects on blood coagulation of molar substitution and C2/C6 ratio of a high molecular weight HES.
Methods. Blood was obtained from 30 healthy patients undergoing elective surgery and mixed with six high molecular weight (700 kDa) HES solutions differing in their molar substitution (0.42 and 0.51) and C2/C6 ratio (2.7, 7 and 14) to achieve 20, 40 and 60% dilution. Blood coagulation was assessed by Thrombelastograph® analysis (TEG) and plasma coagulation tests.Data were compared using a three-way analysis of variance model with repeated measures on the three factors.
Results. Higher molar substitution compromised blood coagulation most (for all TEG parameters, P<0.05). The lowest C2/C6 ratio was associated with the lowest effect on blood coagulation; r (P<0.001), angle 
(P=0.003) and coagulation index (P<0.001). No effect on k and maximum amplitude was observed (P for both >0.50). The higher molar substitution was associated with a lesser increase in PT (P=0.007) and a greater decrease in factor VIII (P=0.010). PTT, functional and antigenic von Willebrand factors were not significantly influenced by molar substitution (P for all >0.20). No significant differences between solutions with the same molar substitution but different C2/C6 ratios were found in plasma coagulation parameters (P for all >0.05).
Conclusions. TEG analysis indicates that high molecular HES with a molar substitution of 0.42 and a C2/C6 ratio of 2.7 has the lowest effect on in vitro human blood coagulation.
Declaration of interest. This study was funded by a grants from B. Braun Melsungen AG and the Department of Anaesthesiology of the University Hospital Lausanne. Marc-Alexander Burmeister and Andreas Fisch are employees of B. Braun AG (Melsungen and Crissier) and Donat R. Spahn is doing paid consulting for B. Braun Medical AG, Switzerland. The Department of Anaesthesiology of the University Hospital Lausanne has done other research projects in collaboration with B. Braun Melsungen AG and has thereby received other funding in the past. The Department of Anesthesiology of the University Hospital Lausanne has also received educational funds from competitor companies.
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