Recombinant human factor VIIa (rFVIIa) in a rabbit stasis model

Diness, V.; Bregengaard, Claus; Erhardtsen, Elisabeth; Hedner, Ulla

doi:10.1016/0049-3848(92)90142-w

Cited by 42 publications

(23 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although rFVIIa did not reduce blood loss in NT rabbits, results of the blood coagulation tests provided evidence for faster coagulation. As in previous observations, rFVIIa shortened PT and aPTT without affecting fibrinogen level, even in the absence of coagulopathy [19,27,28], in humans, rabbits [29] or swine [24].…”

Section: Discussionsupporting

confidence: 75%

Recombinant activated factor VII efficacy and safety in a model of bleeding and thrombosis in hypothermic rabbits: a blind study

Godier

Mazoyer

Cymbalista

et al. 2007

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

To cite this article: Godier A, Mazoyer E, Cymbalista F, Cupa M, Samama C-M. Recombinant activated factor VII efficacy and safety in a model of bleeding and thrombosis in hypothermic rabbits: a blind study. J Thromb Haemost 2007; 5: 244-9.See also Levi M. Recombinant factor VIIa and trauma: treatment that does not leave you in the cold. This issue, pp 242-3.Summary. Background: Recombinant activated factor VII (rFVIIa) is increasingly used to secure hemostasis in hemorrhagic situations in trauma and surgical patients. Hypothermia is often observed in these clinical settings. Objective: To study the efficacy and safety of rFVIIa in hypothermia in a rabbit model of bleeding and thrombosis. Methods: Sixty-nine rabbits were anesthetized, ventilated and monitored for blood pressure, temperature and carotid flow. The Folts model was used: a stenosis (75%) and an injury were carried out on the carotid artery, inducing thrombosis. Blood flow decreased as thrombus size increased until the pressure gradient was such that the thrombus was released and local arterial blood flow was suddenly restored. This is known as a cyclic flow reduction (CFR). After counting baseline CFRs during a 20-min period (P1), rabbits were randomized blindly to one of four groups: normothermic (NT) placebo or rFVIIa (150 lg kg )1 ), hypothermic (HT) (34°C) placebo or rFVIIa. Then CFRs were recorded over a second period (P2). At the end of the experiment, a hepato-splenic section was performed and the amount of blood loss was recorded. After each period, the following were measured: ear immersion bleeding time (BT), hemoglobin, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen. Results: Hypothermia increased BT and blood loss. These effects were reversed by rFVIIa. In NT rabbits, rFVIIa shortened BT but did not reduce blood loss. rFVIIa-treated rabbits bled similarly regardless of temperature. The incidence of CFRs was higher in treated than placebo animals regardless of temperature. rFVIIa decreased PT and aPTT without modifying platelet count or fibrinogen level. Conclusion: Hemostatic efficacy of rFVIIa was maintained in hypothermia. However, the number of CFRs was higher in the rFVIIa-treated group than in the placebo groups, whether for NT or HT rabbits.

show abstract

Section: Discussionsupporting

confidence: 75%

Recombinant activated factor VII efficacy and safety in a model of bleeding and thrombosis in hypothermic rabbits: a blind study

Godier

Mazoyer

Cymbalista

et al. 2007

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

show abstract

“…Because rFVIIa is not known to bind to circulating inactive PLTs in vivo, however, the hemostatic activity of rFVIIa should be restricted to the site of blood vessel injury where TF is exposed and PLTs are locally activated by thrombin. Experimental evidence for this localized effect of rFVIIa has been provided by a comparative study of rFVIIa and the activated prothrombin complex concentrate (APCC) in a rabbit stasis model 38 . In this study, both rFVIIa and APCC promoted clot formation at the site of blood vessel injury.…”

Section: Risk Of Thrombotic Eventsmentioning

confidence: 90%

Recombinant factor VIIa in patients with coagulopathy secondary to anticoagulant therapy, cirrhosis, or severe traumatic injury: review of safety profile

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…This observation is consistent with several studies that found no evidence of systemic activation of coagulation following administration of high doses of factor VIIa. In a rabbit stasis model of thrombosis there was no change in platelet count or plasma fibrinogen levels up to 3 h after administration of high-dose factor VIIa (Diness et al, 1992). Also, a study of two haemophilic patients given five treatments with high-dose factor VIIa showed normal levels of antithrombin III and tissue factor pathway inhibitor with minimal decrease in fibrinogen levels or plasminogen activity (Schmidt et al, 1994).…”

Section: Figmentioning

confidence: 99%

Platelet activity of high‐dose factor VIIa is independent of tissue factor

et al. 1997

View full text Add to dashboard Cite

High‐dose recombinant factor VIIa has been successfully used as therapy for haemophiliacs with inhibitors. The mechanism by which high‐dose factor VIIa supports haemostasis is the subject of some controversy. Postulating a mechanism in which activity is dependent on tissue factor at the site of injury explains the localization of activity but not the requirement for high doses. Postulating a mechanism in which factor VIIa acts on available lipid independently of tissue factor explains the requirement for high doses but not the lack of systemic procoagulant activity. We report that factor VIIa bound weakly to activated platelets (Kd ∼ 90 nm). This factor VIIa was functionally active and could initiate thrombin generation in the presence of plasma concentrations of prothrombin, factor X, factor V, antithrombin III and tissue factor pathway inhibitor. The activity was not dependent on tissue factor. The concentration of factor VIIa required for detectable thrombin generation agreed well with the lowest concentration of factor VIIa required for efficacy in patients. High‐dose factor VIIa may function on the activated platelets that form the initial haemostatic plug in haemophilic patients. These observations are in agreement with clinical trials which have shown that high‐dose factor VIIa was haemostatically effective without causing systemic activation of coagulation.

show abstract

Recombinant human factor VIIa (rFVIIa) in a rabbit stasis model

Cited by 42 publications

References 12 publications

Recombinant activated factor VII efficacy and safety in a model of bleeding and thrombosis in hypothermic rabbits: a blind study

Recombinant activated factor VII efficacy and safety in a model of bleeding and thrombosis in hypothermic rabbits: a blind study

Recombinant factor VIIa in patients with coagulopathy secondary to anticoagulant therapy, cirrhosis, or severe traumatic injury: review of safety profile

Platelet activity of high‐dose factor VIIa is independent of tissue factor

Contact Info

Product

Resources

About