On the mechanism of action of recombinant activated factor VII administered to patients with severe thrombocytopenia and life‐threatening haemorrhage: focus on prothrombin activation

Abstract

Summary. We report the ex vivo effect of recombinant activated factor VII (rFVIIa) on prothrombin activation after whole blood clotting. Two patients with severe thrombocytopenia and life-threatening haemorrhage were successfully managed using a single dose of rFVIIa (90 lg/kg). Western blotting using antiprothrombin antibody showed that rFVIIa did not induce thrombin generation in citrated platelet-poor plasma. Patient sera showed significantly impaired prothrombin activation before and after rFVIIa administration. rFVIIa administration shortened the prothrombin time, activated partial thromboplastin time and Ivy bleeding time, and normalized the clot retraction. These data indicate that rFVIIa accelerated thrombin generation without significant increase of generated thrombin.

Biochemistry and clinical pharmacology of new anticoagulant agents

“…The need for antidote or for a rapid and safe haemostatic method is more urgent in the case of fondaparinux, which is actually being introduced in the daily clinical practice. An attractive alternative could be the use of rFVIIa (Novoseven®), which has been show to be an effective and safe haemostatic agent in a variety of clinical conditions without inducing increased thrombin generation [28]. Recent in vitro experiments from our group showed that rFVIIa does not modify the inhibition of the endogenous thrombin potential induced by therapeutic concentrations of fondaparinux, but it significantly accelerates the generation of thrombin [11].…”

Heterogeneity of Synthetic Factor Xa Inhibitors

“…Non-specific hemostatic agents such as FEIBA, prothrombin complex concentrate and rFVIIa have been considered for life-threatening bleeding. rFVIIa (Novoseven®) has been shown to be an effective and safe hemostatic agent in a variety of clinical conditions without inducing increased thrombin generation [127][128][129]. Recent in vitro experiments and ex vivo observations in healthy volunteers showed that rFVIIa does not modify the inhibition of the endogenous thrombin potential induced by therapeutic concentrations of fondaparinux in human plasma, but it significantly accelerates the generation of thrombin [130,131].…”

Recombinant activated factor VII for severe uterine bleeding after chemotherapy in a woman with acute myeloid leukemia

“…Flow-cytometric analysis revealed CD33, CD34 and HLA DR positivity of the blasts, and acute myeloid leukemia M0 (by FrenchAmerican-British classification) was diagnosed. The MITUS regimen consisting of daunorubicin 45 mg/m 2 [1][2][3], cytarabine (ARA-C) 100 mg/m 2 [1][2][3][4][5][6][7], high-dose cytarabine (HIDAC) 2 g/m 2 [8][9][10] was given.…”

“…It can activate factor X to activated factor X (FXa), as well as factor IX to activated factor IX. FXa, in complex with other factors, then converts prothrombin to thrombin, which leads to the formation of a hemostatic plug by converting fibrinogen to fibrin and thereby inducing local hemostasis [2]. rFVIIa has additionally been considered a universal haemostatic agent, prompting its use in the management of severe uncontrolled surgical bleeding in patients without pre-existing coagulopathies [3].…”