Mechanism of Action of Recombinant Activated Factor VII

Lisman, Ton; Groot, Philip G. de

doi:10.1111/j.1778-428x.2003.tb00093.x

Cited by 3 publications

(1 citation statement)

References 72 publications

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“…Although convincing clinical evidence for the efficacy of rFVIIa in its various applications is rapidly accumulating, relatively little is known about its mechanism of action (reviewed in [16]). It is generally assumed that rFVIIa enhances thrombin generation at the site of vascular damage.…”

Section: Introductionmentioning

confidence: 99%

Recombinant factor VIIa enhances platelet adhesion and activation under flow conditions at normal and reduced platelet count

Lisman

Adelmeijer

Cauwenberghs

et al. 2005

Journal of Thrombosis and Haemostasis

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To cite this article: Lisman T, Adelmeijer J, Cauwenberghs S, van Pampus ECM, Heemskerk JWM, de Groot PG. Recombinant factor VIIa enhances platelet adhesion and activation under flow conditions at normal and reduced platelet count. J Thromb Haemost 2005; 3: 742-51.Summary. Background: Recombinant factor VIIa (rFVIIa), which was developed for treatment of inhibitor-complicated hemophilia, appears suitable as prohemostatic agent in other clinical disorders including patients with thrombocytopenia. It is generally accepted that rFVIIa functions by enhancement of thrombin generation at the site of injury. It is, however, unknown if and how this affects platelet adhesion and aggregation. Objectives: To determine the effect of rFVIIamediated thrombin generation on platelet adhesion and aggregation under flow conditions at normal and reduced platelet counts. Methods: Washed platelets and red cells were combined to obtain plasma-free blood with different platelet counts. The reconstituted blood was perfused over a collagenor fibrinogen-coated surface in the absence or presence of a thrombin generating system consisting of purified coagulation factors rFVIIa, factor (F)X and prothrombin. Results: Addition of coagulation factors rFVIIa, FX and prothrombin to washed platelets and red cells enhanced platelet adhesion and aggregation to collagen and adhesion and spreading to fibrinogen at normal platelet count and at platelet numbers as low as 10 000 lL )1. rFVIIa-mediated thrombin generation enhanced the activation state of platelets as measured by intracellular calcium fluxes, and enhanced the exposure of procoagulant phospholipids as measured by annexin A5 binding. Conclusions: Taken together, increased platelet adhesion and aggregation by rFVIIa-mediated thrombin formation may explain the therapeutic effects of rFVIIa in thrombocytopenic conditions and in patients with a normal platelet count by (i) enhancement of primary hemostasis and (ii) enhancement of procoagulant surface leading to elevated fibrin formation.

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Section: Introductionmentioning

confidence: 99%

Recombinant factor VIIa enhances platelet adhesion and activation under flow conditions at normal and reduced platelet count

Lisman

Adelmeijer

Cauwenberghs

et al. 2005

Journal of Thrombosis and Haemostasis

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Efficacy and safety of activated recombinant factor VII in cardiac surgical patients

Hardy

Bélisle

Linden

2009

Current Opinion in Anaesthesiology

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At present, the generalized use of rFVIIa to prevent or to control excessive bleeding after cardiac surgery cannot be recommended. The decision to administer a potent hemostatic such as rFVIIa outside its recognized prescribing indications should be made with caution by well informed physicians and discussed with the patient. Patients should be informed about knowledge gaps and pertinent risks, which are both important in the case of rFVIIa.

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Use of recombinant factor VIIa in the treatment of massive retroperitoneal bleeding due to severe necrotizing pancreatitis

Stefanović

Mijatović

et al. 2009

VOJNOSANIT PREGL

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Although application of rFVIIa is still in the initial clinical phase, and the experience is based mainly on uncontrolled series as well as on individual observations, it seems that this drug can be promising, potent and attractive adjunctive prohemostatic agent. This drug may play a beneficial role in the treatment of serious and unresponsive, "nonsurgical", life-threatening bleeding due to severe acute necrotizing pancreatitis.

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Mechanism of Action of Recombinant Activated Factor VII

Cited by 3 publications

References 72 publications

Recombinant factor VIIa enhances platelet adhesion and activation under flow conditions at normal and reduced platelet count

Recombinant factor VIIa enhances platelet adhesion and activation under flow conditions at normal and reduced platelet count

Efficacy and safety of activated recombinant factor VII in cardiac surgical patients

Use of recombinant factor VIIa in the treatment of massive retroperitoneal bleeding due to severe necrotizing pancreatitis

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