Effects of hextend hemodilution on plasma coagulation kinetics in the rabbit: Role of Factor XIII-mediated fibrin polymer crosslinking

Background. Hydroxyethyl starch administration has been associated with decreases in hemostasis and has recently been demonstrated to decrease fibrinogen (FI)-thrombin-(FIIa)-Factor XIII (FXIII) interactions in vitro in human plasma. Thus, the purpose of the present study was to determine the effect of in vivo hemodilution with Hextend (6% hydroxyethyl starch, mean molecular weight 450 kDa) on plasma coagulation kinetics. Materials and methods. Eight male, New Zealand White rabbits were intravenously administered with 20 ml/kg of Hextend. Citrated plasma was obtained before, 1 min after, and 1 h after hemodilution. Thrombelastographic analyses were performed, with clot initiation (11, sec), clot propagation (alpha, degrees), and clot strength (shear elastic modulus, G, dynes/cm(2)) determined over 20 min. Samples were celite-activated and had either with addition or without additions of FI, FIIa or activated FXIII (FXIIIa) to restore protein content to prediluted values. Results. There was no significant difference in R values observed before (229 +/- 30), 1 min after (241 +/- 54), and 1 h after (214 +/- 42) hemodilution. Prediluted a values (75.2 +/- 1.9) were significantly decreased 1 min (53.3 +/- 5.9) and 1 h after hemodilution (56.1 +/- 10.2). Prediluted G values (1992 +/- 434) were significantly reduced I min (532 195) and 1 h after (630 +/- 297) hemodilution. FI, FIIa, and FXIIIa addition significantly decreased R values after hemodilution. a and G values were significantly improved by FI and FXIIIa after hemodilution. FIIa addition did not significantly affect a or G. Conclusions. Hextend hemodilution in rabbits maintains clot initiation by diminishing both FIIa-FI and FXIIIa-fibrin interactions, whereas clot propagation and strength were reduced by diminished FXIIIa-fibrin interactions. (c) 2005 Elsevier Inc. All rights reserved.