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.


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 (R, 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 alpha 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 (1,992 +/- 434) were significantly reduced 1 min (532 +/- 195) and 1 h after (630 +/- 297) hemodilution. FI, FIIa, and FXIIIa addition significantly decreased R values after hemodilution. alpha and G values were significantly improved by FI and FXIIIa after hemodilution. FIIa addition did not significantly affect alpha 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.
Nielsen
Vance G
VG
Department of Anesthesiology, University of Alabama at Birmingham, 619 South 19th Street, 35249-6810, USA. vnielsen@uab.edu
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001784:Blood Gas Analysis; D005337:Fibrin / Q000378:metabolism*; D006438:Hemodilution; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D023421:Models, Animal; D010952:Plasma Substitutes / Q000494:pharmacology*; D011817:Rabbits; D013925:Thromboplastin / Q000378:metabolism*
D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D005337:Fibrin; D013925:Thromboplastin