Hemodilution with albumin, but not Hextend, results in hypercoagulability as assessed by Thrombelastography in rabbits: role of heparin-dependent serpins and factor VIII complex.
Isovolemic hemodilution (IVHD) has been advocated as an effective method of reducing the need for transfusion but has been associated with hypercoagulability. We tested the hypothesis that IVHD enhances hemostatic function by decreasing circulating antithrombin activity in rabbits. Furthermore, it was determined whether different replacement solutions would affect hemostasis. Sedated rabbits were randomly assigned to groups that underwent IVHD (40% blood volume removed) with 5% human albumin (n = 10) or a 6% hetastarch solution (Hextend). Antithrombin and Factor VIII complex (VIII:C) activities were determined, and thrombelastography(R) was performed with or without platelet inhibition. IVHD resulted in a significant (P < 0.05) decrease in antithrombin (32%-39%) without fluid-specific differences observed. VIII:C did not change in the albumin group, whereas the hetastarch group had a significant (P < 0.05) decrease (43%) in VIII:C that was also significantly (P < 0.05) less than the albumin group. The time to clot initiation was decreased, and the rate of clot formation increased significantly via thrombelastography(R) in albumin animals. No significant change in clot kinetics was observed in hetastarch animals. In rabbits, the primary determinant of hemostasis after IVHD was the interaction of changes in antithrombin activity and VIII:C. These data serve as a rational basis to determine whether IVHD-mediated hypercoagulability encountered clinically may be attenuated or exacerbated by the choice of colloid administered.


CONCLUSIONS
Isovolemic hemodilution (IVHD) is associated with hypercoagulability. Rabbits hemodiluted with albumin, but not Hextend, became hypercoagulable secondary to a loss of antithrombin activity with simultaneous maintenance of Factor VIII complex activity (VIII:C). Hextend-treated animals had proportionate decreases in both antithrombin activity and VIII:C. IVHD-mediated hypercoagulability encountered clinically may be attenuated or exacerbated by the choice of colloid administered.
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001778:Blood Coagulation Disorders / Q000097:blood* / Q000139:chemically induced*; D001784:Blood Gas Analysis; D005169:Factor VIII / Q000494:pharmacology*; D006438:Hemodilution / Q000379:methods*; D006439:Hemodynamics / Q000187:drug effects; D006493:Heparin / Q000502:physiology*; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D008297:Male; D010952:Plasma Substitutes / Q000494:pharmacology*; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000502:physiology*; D015843:Serpins / Q000502:physiology*; D012709:Serum Albumin / Q000494:pharmacology*; D013916:Thrombelastography
D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D012709:Serum Albumin; D005169:Factor VIII; D006493:Heparin