A calcium-containing electrolyte-balanced hydroxyethyl starch (HES) solution is associated with higher factor VIII activity than is a non-balanced HES solution, but does not affect von Willebrand factor function or thromboelastometric measurements--results of a model of in vitro haemodilution

Abstract

Background: Hydroxyethyl starch (HES) is known to impair blood coagulation. The impact of calcium-containing, balanced carrier solutions of HES on coagulation is controversial. We investigated the effects of increasing degrees of haemodilution with modern 6%, electrolyte-balanced HES vs non-balanced HES on coagulation in vitro, and compared the balanced HES to a balanced crystalloid solution for an internal control.

Materials and methods: Blood samples from ten healthy volunteers were diluted in vitro by 20%, 40% and 60% with either calcium-containing balanced 130/0.42 HES, non-balanced 130/0.4 HES or balanced crystalloid. In all samples, blood counts, prothrombin time ratio, activated partial thromboplastin time, ionized calcium, factor VIII activity, von Willebrand factor antigen, von Willebrand factor collagen binding activity, and von Willebrand factor activity were determined, and activated rotational thromboelastometry (EXTEM and FIBTEM assays) was performed.

Results: Haemodilution impaired coagulation in a dilution-dependent manner as determined by both conventional laboratory assays and thromboelastometry. Ionized calcium increased with balanced HES (p≤0.004), but decreased with non-balanced HES (p≤0.004). Prothrombin time ratio (p≤0.002) and factor VIII levels (p=0.001) were better preserved with balanced HES than with non-balanced HES in dilutions ≥40%. Thromboelastometry showed no differences between values in blood diluted with the balanced or non-balanced HES.

Discussion: In vitro, a balanced calcium-containing carrier solution of 6% HES 130/0.42 preserved coagulation better than did non-balanced HES 130/0.4 as quantified by conventional coagulation assays, but not in activated thromboelastometry. One explanation could be the increased ionized calcium levels after dilution with calcium-containing carrier solutions.

Figure 1

Effect of in vitro haemodilution on thromboelastometry parameters. CT, CFT and MCF of the EXTEM-test, and MCF of the FIBTEM-test of activated rotational thromboelastometry before and after progressive in vitro haemodilution with balHES, nbalHES, and balCry. Reference ranges for thromboelastometry parameters (shaded area) were taken from a multi-centre investigation on reference ranges for ROTEM^® . Results are presented as box-and-whisker plots. The superscripts show the statistical significance (p≤0.008) of any differences if applicable: 1 = significant in comparison to balHES, 2 = significant in comparison to nbalHES, 3 = significant in comparison to balCry. Abbreviations: bal: balanced; Cry: crystalloid; CFT: clot formation time, CT: clotting time, HES: hydroxyethyl starch, MCF: maximum clot firmness, nbal: non-balanced.