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Factor VII Deficiency Medication

  • Author: Muhammad A Mir, MD, FACP; Chief Editor: Perumal Thiagarajan, MD  more...
 
Updated: May 12, 2016
 

Medication Summary

Recombinant factor VIIa

rFVIIa is licensed by the US Food and Drug Administration for the treatment of bleeding in individuals with hemophilia A and B with acquired inhibitors and for persons with congenital factor VII deficiency. rFVIIa is produced in vitro in baby hamster kidney cells that are transfected with F7.[31]

Although originally developed for the treatment of inhibitor-complicated hemophilia A and B, novel indications for rFVIIa (based on case reports and smaller clinical trials) include use in patients with liver disease, thrombocytopenia, or qualitative platelet dysfunction and in patients with no coagulation disorders who are bleeding as a result of extensive surgery or major trauma.[5, 32, 14, 33, 34] Use of rFVIIa to control bleeding has increased among patients with intracranial bleeding, cardiac surgery, prostatectomy, trauma, and liver transplantation over the past few years.[22] The benefits of rFVII is uncertain, and no mortality reduction is seen. The various dosages used in the above-mentioned conditions vary and are outlined in the review by Logan et al.[35]

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Antihemophilic agents, drug-product derivatives

Class Summary

The mechanism by which factor VIIa maintains normal hemostasis is unknown. Clot-promoting activity of rFVIIa is primarily mediated through the tissue factor pathway, although direct activation of primary hemostasis may also occur.

Tissue factor-dependent and tissue factor-independent enhancement of thrombin generation have been suggested to play a role.[36, 33] Factor VIIa alone, in the absence of tissue factor, can generate factor IXa and factor Xa on the surface of activated platelets, which, in turn, induces the coagulation cascade to form thrombin.[37]

Mechanism of action of rFVIIa in patients with Glanzmann thrombasthenia and Bernard-Soulier syndrome is thought to be from thrombin generation on the surface of platelets, resulting in faster platelet activation and aggregation.[5]

In a recent study that evaluated rFVIIa in patients with acute intracerebral hemorrhage, the mortality was relatively reduced by 38% at 3 months when rFVIIa was administered within 4 hours of the hemorrhage. Accelerated thrombin generation from activated platelets at the sites of ruptured arterioles after administration of rFVIIa provides hemostatic effect and improved the outcome of these patients.[38]

By similar mechanisms, rFVIIa is also effective at controlling refractory bleeding in trauma patients.[39] Gastrointestinal bleeding in patients with cirrhosis has responded positively to rFVIIa.

Coagulation factor VIIa, recombinant (NovoSeven)

 

Supplied in 1.2- and 4.8-mg vials. Half-life of rFVIIa is 2-3 h. Cleared from plasma more rapidly in children than in adults.

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Blood products

Class Summary

These agents are indicated for the correction of abnormal hemostatic parameters.

Fresh frozen plasma (FFP, Octaplas)

 

FFP is used to correct coagulation factor deficiency when hemostasis is urgently required. FFP is separated within 8 h of whole blood collection and frozen at -18°C. Each unit of FFP contains 200 U of each coagulation factor. Volume transfused should correct factor VII level to at least 30% of normal levels. Octaplas is a solvent detergent treated, pooled FFP.

Factor IX complex (Proplex, BeneFix, Hemodyne)

 

Contains factor VII 68-91 U/mL. Viral inactivation with dry heat (60°C [140°F] for 144 h). Prothrombin complex concentrates contain variable amounts of factors II, VII, IX, and X.

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Antifibrinolytic agents

Class Summary

These agents increase circulating plasmin levels and decrease plasminogen levels.

Aminocaproic acid (Amicar)

 

Inhibits fibrinolysis via inhibition of plasminogen activator substances and, to a lesser degree, through antiplasmin activity. Main problem is that the thrombi that form during treatment are not lysed and effectiveness is uncertain.

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Contributor Information and Disclosures
Author

Muhammad A Mir, MD, FACP Assistant Professor of Medicine (Hematology, Blood/Marrow Transplant) Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

Muhammad A Mir, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Hematology, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada, American Clinical and Climatological Association, International Society of Blood Transfusion

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.

Chief Editor

Perumal Thiagarajan, MD Professor, Department of Pathology and Medicine, Baylor College of Medicine; Director, Transfusion Medicine and Hematology Laboratory, Michael E DeBakey Veterans Affairs Medical Center

Perumal Thiagarajan, MD is a member of the following medical societies: American College of Physicians, American Society for Clinical Investigation, Association of American Physicians, American Society for Biochemistry and Molecular Biology, American Heart Association, American Society of Hematology, Royal College of Physicians

Disclosure: Nothing to disclose.

Additional Contributors

Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

Acknowledgements

Francisco J Hernandez-Ilizaliturri, MD Associate Professor of Medicine, Department of Medicine, Assistant Professor of Immunology, Department of Immunology, Roswell Park Cancer Institute, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Francisco J Hernandez-Ilizaliturri, MD is a member of the following medical societies: American Association for Cancer Research and American Society of Hematology

Disclosure: Nothing to disclose.

Ganapathy S Krishnan, MBBS Fellow, Department of Hematology and Oncology, Michigan State University

Ganapathy S Krishnan, MBBS is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Jeyanthi Ramanarayanan, MD Assistant Professor, Medical Oncology, Veterans Affairs Medical Center of Buffalo

Jeyanthi Ramanarayanan, MD is a member of the following medical societies: American Association of Physicians of Indian Origin and American Society of Hematology

Disclosure: Nothing to disclose.

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Factor VII. Intrinsic and extrinsic pathways of coagulation. Factor VII/tissue factor complex activates factor IX and factor X. Factor IXa along with factor VIIIa results in formation of more factor Xa. Factor Xa along with factor Va converts prothrombin to thrombin.
 
 
 
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