Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven®)

• Published in: British journal of anaesthesia : BJA Vol. 101; no. 3; pp. 324 - 331
• Main Authors: Viuff, D., Lauritzen, B., Pusateri, A.E., Andersen, S., Rojkjaer, R., Johansson, P.I.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.2008; Oxford University Press; Oxford Publishing Limited (England)
• Subjects: acidosis; Acidosis - blood; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Bleeding Time; blood; blood, haemodilution; Cardiovascular; complications; complications, acidosis; Dose-Response Relationship, Drug; Factor VIIa - pharmacology; Female; haemodilution; haemostatic response; Hemodilution; Hemostasis - drug effects; Hemostatics - pharmacology; Humans; Hydrogen-Ion Concentration; Hydroxyethyl Starch Derivatives - pharmacology; hypothermia; Hypothermia - blood; In Vitro Techniques; measurement techniques; measurement techniques, thromboelastography; Medical sciences; Molecular Weight; Plasma Substitutes - pharmacology; Rabbits; Recombinant Proteins - pharmacology; rFVIIa; surgery; surgery, haemostatic response; Thrombelastography - drug effects; thromboelastography; complications, acidosis; surgery, haemostatic response; measurement techniques, thromboelastography; rFVIIa; hypothermia; blood, haemodilution; acidosis; hypothermia; measurement techniques; thromboelastography; rFVlla; surgery; Acid base balance disorder; blood; haemodilution; complications; Metabolic disorder; Measurement technique; Surgery; Anesthesia; Complication; haemostatic response; Acidosis; Hypothermia
• ISSN: 0007-0912; 1471-6771
• DOI: 10.1093/bja/aen175

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. 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°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. 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. Efficacy of rFVIIa was affected by the degree of haemodilution and type of volume expander, but not by acidosis or hypothermia.