The use of recombinant factor VIIa in the treatment of bleeding disorders

Roberts, Harold R.; Monroe, Dougald M.; White, Gilbert

doi:10.1182/blood-2004-06-2223

Cited by 248 publications

(216 citation statements)

References 81 publications

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“…rfVIIa facilitates hemostasis by activating factor X directly on the platelet surface thereby bypassing the tenase complex. 37 The half-life is 2.3 hours in adults but potentially shorter in children. 38 Attempts to protein engineer rfVIIa to have a longer circulation time are currently underway.…”

Section: Treatment Of Acute Bleedingmentioning

confidence: 99%

How we treat a hemophilia A patient with a factor VIII inhibitor

Kempton

White

2009

Blood

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150

144

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The most significant complication of treatment in patients with hemophilia A is the development of alloantibodies that inhibit factor VIII activity. In the presence of inhibitory antibodies, replacement of the missing clotting factor by infusion of factor VIII becomes less effective. Once replacement therapy is ineffective, acute management of bleeding requires agents that bypass factor VIII activity. Long-term management consists of eradicating the inhibitor through immune tolerance. Despite success in the treatment of acute bleeding and inhibitor eradication, there remains an inability to predict or prevent inhibitor formation. Ideally, prediction and ultimately prevention will come with an improved understanding of how patientspecific and treatment-related factors work together to influence anti-factor VIII antibody production. (Blood. 2009;113: 11-17)

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Section: Treatment Of Acute Bleedingmentioning

confidence: 99%

How we treat a hemophilia A patient with a factor VIII inhibitor

Kempton

White

2009

Blood

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150

144

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“…The TF-rFVIIa complex then activates the remainder of the common coagulation cascade via activated factor X. Alternatively, rFVIIa may bind to activated platelets, which also concentrates factor X activation to sites of tissue injury. 7 The factor Xa generated by these two mechanisms ultimately drives the thrombin burst, which cleaves fibrinogen to fibrin, thus initiating the formation of the fibrin meshwork critical to secondary coagulation and clot stabilization. The potential role for rFVIIa in tissue factorindependent clotting has raised concern for its site specificity and the risk for off-target thrombosis.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Recombinant Factor VIIa: An Assessment of Evidence Regarding Its Efficacy and Safety in the Off-Label Setting

Logan

Goodnough

2010

Hematology

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Recombinant human factor VIIa (rFVIIa) is approved by the US Food and Drug Administration for use in the setting of hemorrhage associated with factor VIII or factor IX inhibitors in patients with congenital or acquired hemophilia. This indication represents only a small number of bleeding conditions. Since it became available, rFVIIa has been increasingly used in the management of off-label indications, ranging from emergent hemostasis in traumatic hemorrhage to prophylactic hemostasis in patients undergoing major surgery. Prominent off-label indications include the management of patients with coagulopathies, such as occurs in trauma patients experiencing massive and uncontrolled hemorrhage, and in patients undergoing cardiovascular surgery with cardiopulmonary bypass. Other occasions for use occur in patients with intact coagulation systems, with nontraumatic intracranial hemorrhage being the most common in this group. Uncertainties regarding the efficacy and safety associated with use of rFVIIa in these off-label scenarios have led to evidence-based assessments of patient outcomes, including mortality, the rate of thromboembolic adverse events, and posttreatment functional status. We review the evidence regarding the efficacy and safety of this important, but controversial, hemostatic agent in the off-label setting.

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“…A At the same time, several groups have recommended guidelines for the 'off-label' use of rFVIIa in certain non-hemophiliac patients. [6][7][8][9][10][11] In none of these, however, was the focus cardiac surgery.…”

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confidence: 99%

The role of recombinant factor VIIa in on-pump cardiac surgery: Proceedings of the Canadian Consensus Conference

Karkouti

Beattie

Crowther

et al. 2007

Can J Anesth/J Can Anesth

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Purpose: Recombinant activated factor VII (rFVIIa) is currently not approved by Health Canada or the Food and Drug Administration for treating excessive blood loss in nonhemophiliac patients undergoing on-pump cardiac surgery, but is increasingly being used "off-label" for this indication. A Canadian Consensus Conference was convened to generate recommendations for rFVIIa use in on-pump cardiac surgery. Methods: The panel undertook a literature review of the use of rFVIIa in both cardiac and non-cardiac surgery. Appropriateness, timing, and dosage considerations were addressed for three cardiac surgery indications: prophylactic, routine, and rescue uses. Recommendations were based on evidence from the literature and derived by consensus following recognized grading procedures. Results: The panel recommended against prophylactic or routine use of rFVIIa, as there is no evidence at this time that the benefits of rFVIIa outweigh its potential risks compared with standard hemostatic therapies. On the other hand, the panel made a weak recommendation (grade 2C) for the use of rFVIIa (one to two doses of 35-70 µg·kg -1 ) as rescue therapy for blood loss that is refractory to standard hemostatic therapies, despite the lack of randomized controlled trial data for this indication. Conclusions: In cardiac surgery, the risks and benefits of rFVIIa are unclear, but current evidence suggests that its benefits may outweigh its risks for rescue therapy in selected patients. Methodologically rigorous studies are needed to clarify its riskbenefit profile in cardiac surgery patients. 200 Elizabeth Street, Toronto, Ontario M5G 2C4,; E-mail: keyvan.karkouti@uhn.on.ca Disclosure statement: Novo Nordisk (Mississauga, Ontario, Canada), the makers of rFVIIa, funded this project through an unrestricted educational grant. Novo Nordisk was not involved in the selection of the members of the consensus panel, nor were they involved in the panel's review process, deliberations, conclusions, or manuscript preparation. The panel's chair selected the panel members, with the objective of achieving relevant multi-disciplinary expertise (i.e., anesthesiology, cardiac surgery, hematology, intensive care, and clinical epidemiology). The manuscript was primarily written by the panel chair (Keyvan Karkouti) and was approved by all of the panel members. All of the authors received an honorarium for attending the consensus conference.

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The use of recombinant factor VIIa in the treatment of bleeding disorders

Cited by 248 publications

References 81 publications

How we treat a hemophilia A patient with a factor VIII inhibitor

How we treat a hemophilia A patient with a factor VIII inhibitor

Recombinant Factor VIIa: An Assessment of Evidence Regarding Its Efficacy and Safety in the Off-Label Setting

The role of recombinant factor VIIa in on-pump cardiac surgery: Proceedings of the Canadian Consensus Conference

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