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Recombinant activated factor VII decreases bleeding without increasing arterial thrombosis in rabbits

[Le facteur VII recombinant activé diminue le saignement sans augmenter la thrombose artérielle chez le lapin]

Maurizio Fattorutto, MD^*, Sandrine Tourreau-Pham, MD^*, Elisabeth Mazoyer, MD, Philippe Bonnin, MD PhD, Martine Raphaël, MD PhD, Françoise Morin, MD, Michel Cupa, MD^* and Charles-Marc Samama, MD PhD^*

^* From the Department of Anesthesiology and Intensive care,
the Laboratory of Hematology, and
the Blood Transfusion Unit, (Etablissement Français du Sang, site Avicenne), Hôpital Avicenne, Bobigny; and
the Department of Functional Investigations, Hôpital Lariboisière, Paris, France.

Address correspondence to: Pr. Charles Marc Samama, Département d’Anesthésie-Réanimation, Hôpital Avicenne, 125, route de Stalingrad, 93009 Bobigny cedex, France. Phone: 33 1 48 95 55 91; Fax: 33 1 48 95 55 89; E-mail: cmsamama{at}invivo.edu

Purpose: 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].

Conclusion: rFVIIa led to a decrease in BT and microvascular bleeding but did not significantly affect arterial thrombosis in rabbits.

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