Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven).
BACKGROUND
A range of plasma volume expanders is used clinically, often in settings where haemostasis may already be impaired. The haemostatic agent, recombinant activated factor VII (rFVIIa, NovoSeven), may be used to improve haemostasis but potential interactions with different volume expanders are poorly understood.


METHODS
Clot formation was measured by thromboelastography (TEG) using blood from healthy volunteers. In vitro effects of rFVIIa with haemodilution, acidosis, and hypothermia were examined. Conditions were induced by dilution with NaCl (0.9%), lactated Ringer's solution, albumin 5%, or hydroxyethyl starch (HES) solutions [MW (molecular weight) 130-670 kDa]; by adjusting pH to 6.8 with 1 M HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulphonic acid) buffer; or by reducing temperature to 32 degrees C. We also studied the effect of low vs high MW HES (MW 200 vs 600 kDa) and rFVIIa on in vivo bleeding time (BT) in rabbits.


RESULTS
Haemodilution progressively altered TEG parameters. rFVIIa improved TEG parameters in the presence of acidosis, hypothermia or 20% haemodilution (P<0.05). At 40% haemodilution, the rFVIIa effect was diminished particularly with high MW HES. In vivo, rFVIIa shortened the BT (P<0.05) with low but not high MW HES.


CONCLUSIONS
Efficacy of rFVIIa was affected by the degree of haemodilution and type of volume expander, but not by acidosis or hypothermia.
Hemostasis Pharmacology, Novo Nordisk A/S, Novo Nordisk Park, 2760 Måløv, Denmark. dviu@novonordisk.com
D
D
Viuff
B
B
Lauritzen
A E
AE
Pusateri
S
S
Andersen
R
R
Rojkjaer
P I
PI
Johansson
D000138:Acidosis / Q000097:blood*; D000818:Animals; D001760:Bleeding Time; D004305:Dose-Response Relationship, Drug; D015942:Factor VIIa / Q000494:pharmacology*; D005260:Female; D006438:Hemodilution; D006487:Hemostasis / Q000187:drug effects; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology; D007035:Hypothermia / Q000097:blood*; D066298:In Vitro Techniques; D008970:Molecular Weight; D010952:Plasma Substitutes / Q000494:pharmacology; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013916:Thrombelastography / Q000187:drug effects
D006490:Hemostatics; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa