Haemodilution-induced enhancement of coagulation is attenuated in vitro by restoring antithrombin III to pre-dilution concentrations

Abstract

Moderate haemodilution enhances coagulability in vitro and in vivo as measured by thrombelastography (TEG). The mechanism has never been established. We have conducted an in vitro study to determine whether the effect can be moderated or prevented when the reduction in antithrombin III caused by dilution is prevented by supplementation. Blood from 20 volunteers was divided into four samples. One sample was not diluted and served as control (C). Another was diluted (by 20%) with saline (S). The third was diluted by 20% with saline plus two units of antithrombin (AT III) (SA). The fourth remained undiluted, with two units of added AT III (CA). Coagulation was measured in all four samples using the TEG. In a separate laboratory study, the levels of AT III were measured in control samples and compared with levels after 20% dilution, and 20% dilution with two units of AT III added to the diluent. Enhanced coagulation was demonstrated in saline-diluted samples (S) by shortening of r- and k-times, and increased alpha angle. In the SA samples, r-time shortening was prevented; k-time shortening and alpha-angle increase persisted, but to a reduced degree (difference from saline-only dilution P<0.051). There were no differences between samples C and CA. A predictable drop of AT III (24.2%) occurred with saline dilution, while AT III levels in the AT III/Saline group were similar to the undiluted control. Haemodilution-induced coagulation enhancement is attenuated, but not prevented, if AT III levels are maintained in the normal range. This is in keeping with the established concept of an antithrombin threshold preventing positive coagulation feedback into the intrinsic pathway.