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

Gerotziafas, Grigoris T.; Zervas, Kostas; Arzoglou, P.; Karavaggeli, Eli; Parashou, Stella; Dreden, Patrick Van; Christakis, John; Samama, M

doi:10.1046/j.1365-2141.2002.03437.x

Cited by 29 publications

(27 citation statements)

References 9 publications

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“…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].…”

Section: Antidotementioning

confidence: 99%

Biochemistry and clinical pharmacology of new anticoagulant agents

Samama¹,

Gerotziafas²,

Elalamy³

et al. 2002

Pathophysiol Haemos Thromb

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Section: Antidotementioning

confidence: 99%

Biochemistry and clinical pharmacology of new anticoagulant agents

Samama¹,

Gerotziafas²,

Elalamy³

et al. 2002

Pathophysiol Haemos Thromb

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“…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].…”

Section: Antidote For the New Antithrombotic Agentsmentioning

confidence: 99%

Heterogeneity of Synthetic Factor Xa Inhibitors

Gerotziafas

Samama²

2005

CPD

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Heparins and vitamin K antagonists are the landmarks of antithrombotic treatment. Both of them were discovered by serendipity; they are multi-targeted drugs and share several limitations. New molecules have been designed in order to be both more selective concerning their biological target and more homogeneous in their biochemical structure aiming at an improved benefit/risk ratio in the treatment of thrombotic disease. In this article, we will review the pharmacological characteristics of the new synthetic direct or antithrombin dependent inhibitors of FXa in the light of the modern concept of blood coagulation process. We will also present the most recent data from the clinical trials with synthetic inhibitors of FXa. Among them, the synthetic pentasaccharide fondaparinux is the first synthetic and specific FXa inhibitor, which has been approved by health authorities in Europe and in the USA for the prophylaxis of venous thromboembolism in major orthopaedic surgery and is being approved for the treatment of pulmonary embolism and DVT as a single daily subcutaneous injection. The phase II dose-finding trial of the "meta-pentasaccharide" idraparinux administered subcutaneously once weekly in the secondary prevention of VTE has been completed. DX-9065a is the first direct synthetic inhibitor which has been studied in patients with coronary disease. Razaxaban, BAY59-7939, ZK-807834 and JTV-803 are orally active direct FXa inhibitors, which have been studied in phase II trials. Several other synthetic direct inhibitors of FXa (such as FXV673, YM60828, KFA-1411) are in a pre-clinical stage of research. From a clinical point of view, the results of recent trials with the synthetic specific FXa inhibitors clearly show that the inhibition of FXa is a critical point in the antithrombotic strategy.

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“…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.…”

Section: Case Reportmentioning

confidence: 99%

“…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].…”

Section: Introductionmentioning

confidence: 99%

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

Erikçi

Öztürk²,

Sayan³

2006

Blood Coagulation &Amp; Fibrinolysis

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Acute hemorrhage is sometimes a serious complication that may arise in patients with acute leukemia as a result of therapy-induced myelosuppression. In most cases, transfusion of platelets and red blood cells are used to manage this clinical entity. These therapeutic interventions are not always successful and a more direct approach to activating the coagulation system can be more effective and, in some instances, life saving. Recombinant activated factor VII (rFVIIa), which is used for management of hemophiliac patients with inhibitors, is a major alternative in such situations. Here we describe the use of rFVIIa in a 41-year-old patient with ongoing vaginal bleeding with acute myeloid leukemia. Our experience indicates that rFVIIa may be an effective salvage treatment in bleeding conditions related to leukemia.

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

Cited by 29 publications

References 9 publications

Biochemistry and clinical pharmacology of new anticoagulant agents

Biochemistry and clinical pharmacology of new anticoagulant agents

Heterogeneity of Synthetic Factor Xa Inhibitors

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

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