Recombinant activated factor VII decreases bleeding without increasing arterial thrombosis in rabbits.
OBJECTIVE
To compare the effects of recombinant activated factor VII (rFVIIa) and platelet-rich plasma (PRP) in an experimental model of bleeding and arterial thrombosis.


METHODS
The Folts model was used in 60 rabbits. After anesthesia, the carotid artery was exposed and a 75% stenosis was induced. A compression injury of the artery triggered a series of cyclic flow reductions (CFRs). After counting baseline CFRs, animals were assigned randomly to one of four groups (n = 15 in each): control, PRP, rFVIIa and placebo. Control animals received 10 mL.kg(-1) of saline while 10 mL.kg(-1) of a hydroxyethyl starch solution (200,000/6%/0.5) were infused in the three other groups. CFRs were measured again, followed by treatment with PRP, rFVIIa or placebo and by a final measurement of CFRs. At the end of each observation period, an ear immersion bleeding time (BT) was measured and a blood sample was drawn for the evaluation of hematological variables. Microvascular bleeding was evaluated at the end of the experiment in grams of blood shed from liver and spleen sections. Results are presented as median (range).


RESULTS
rFVIIa shortened the BT and decreased microvascular bleeding as compared with placebo [60 (35-100) sec vs 110 (50-140) sec, P = 0.0019 and 9 (4-24) g vs 17 (5-28) g, P = 0.002, respectively]. rFVIIa did not increase CFRs [3(0-9) vs |(0-5), P = 0.11].


CONCLUSIONS
rFVIIa led to a decrease in BT and microvascular bleeding but did not significantly affect arterial thrombosis in rabbits.
Département d'Anesthésie-Réanimation, Hôpital Avicenne, 125 route de Stalingrad, 93009 Bobigny cedex, France.
Maurizio
M
Fattorutto
Sandrine
S
Tourreau-Pham
Elisabeth
E
Mazoyer
Philippe
P
Bonnin
Martine
M
Raphaël
Françoise
F
Morin
Michel
M
Cupa
Charles-Marc
CM
Samama
D000818:Animals; D001760:Bleeding Time; D001783:Blood Flow Velocity / Q000187:drug effects; D001792:Blood Platelets; D002339:Carotid Arteries / Q000503:physiopathology; D002341:Carotid Artery Thrombosis / Q000517:prevention & control*; D016893:Carotid Stenosis / Q000503:physiopathology; D004195:Disease Models, Animal; D015942:Factor VIIa / Q000009:adverse effects / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006470:Hemorrhage / Q000188:drug therapy / Q000517:prevention & control*; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage; D008297:Male; D010952:Plasma Substitutes / Q000008:administration & dosage; D010974:Platelet Aggregation / Q000187:drug effects; D011446:Prospective Studies; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use; D012965:Sodium Chloride / Q000008:administration & dosage; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D011994:Recombinant Proteins; D012965:Sodium Chloride; D015942:Factor VIIa