High-Molecular-Weight Hydroxyethyl Starch Accelerates Kallikrein-Dependent Clot Initiation

Abstract

A decrease in reaction time (R; seconds) has been considered a thrombelastographic hallmark of hypercoagulability. However, the cause of changes in R has been influenced by the method of activation (e.g., celite) and the clinical/laboratory setting (e.g., hemodilution). Although antithrombin deficiency has been implicated as a cause of decreased R in unactivated samples after crystalloid dilution, dilution with hydroxyethyl starch (HES) solutions such as Hextend (6% HES solution; average molecular weight 450 kDa) or Voluven (6% HES solution; average molecular weight 130 kDa) has decreased R values in celite-activated samples in vitro and in vivo, with modulation of these R values observed after aprotinin exposure. Thus, this study proposed to define whether HES affects kallikrein-dependent clot initiation. Citrated human plasma was subjected to 0% or 30% dilution with 0.9% NaCl, Hextend, or Voluven, in the absence or presence of aprotinin (200 KIU/mL final concentration). Prekallikrein-deficient (<1% activity) plasma was similarly diluted. After recalcification and celite activation, thrombelastography was performed for determination of R. R in samples without aprotinin diluted with Hextend (mean +/- SD, 132 +/- 6 seconds) was significantly smaller than that in samples with 0% dilution (155 +/- 5 seconds) and 30% dilution with 0.9% NaCl (162 +/- 9 seconds), but was not less than that in Voluven-diluted samples (149 +/- 14 seconds). R significantly increased (28%-68%) in all conditions with aprotinin compared to samples without aprotinin, and Hextend had significantly smaller R compared with that in the other fluids. Lastly, R was not different in experiments with prekallikrein-deficient plasma. These data indicate that Hextend accelerates kallikrein-dependent clot initiation compared with 0.9% NaCl or Voluven.