Sections

Workup

Laboratory Studies

Routine initial hemostatic tests for suspected factor VII deficiency include the following:

Activated partial thromboplastin time (aPTT)
Prothrombin time (PT)
Platelet count

A normal aPTT and a prolonged PT in a patient with a lifelong history of a tendency for mild or severe bleeding is consistent with the diagnosis of factor VII deficiency or the presence of an inhibitor to factor VII.

Bleeding time is usually within the reference range.

With no significant clinical bleeding but a prolonged PT and a normal aPTT, the patient has either mild factor VII deficiency or is taking oral anticoagulants.

To distinguish between factor VII deficiency and the presence of an inhibitor to factor VII, mixing studies are useful. PT testing is repeated using a 1:1 mixture of the patient's plasma and normal plasma. Normal plasma is a source of factor VII; therefore, when such a mixture normalizes the prolonged PT, the patient likely has a deficiency of factor VII. When the mixture still results in a prolonged PT, sometimes after initial correction, an inhibitor to factor VII is probably present.

A specific assay for factor VII, using known factor VII–deficient plasma, is required to confirm the diagnosis. Factor VII antigen can be measured using a radioimmunoassay.

Functional factor VII assays are as follows:

To determine the severity, factor VII activity levels (factor VII:c) are measured using a single-stage, PT-based assay.
The factor VII:c assay uses the ability of tissue factor to promote the conversion of factor VII to factor VIIa and measures the total clotting activity of factor VII and factor VIIa. Results can vary dramatically depending on the source of tissue factor used in the in vitro assay.

Immunological factor VII assays can be used to measure factor VII:Ag (antigen levels). This can be an enzyme-linked immunosorbent assay or an immunoradiometric assay.

A factor VIIa:c assay is used to evaluate therapeutic factor VIIa levels. This is an enzyme-linked immunosorbent assay using specific antibodies or soluble mutant tissue factor that is insensitive to native factor VII but that serves as a cofactor for factor VIIa catalyzed activation of factor X.

A more definitive approach involves genetic analysis of mutant genes in involved families.

Imaging Studies

CT scan and ultrasound have been used to localize, quantify, and serially monitor the location and response of bleeding to specific therapy.

Plain radiography is not useful for evaluating soft tissue damage.

MRI can be used to assess soft tissue damage; is a better modality to evaluate joint effusion, synovial hyperplasia, and cartilage loss; and can help localize the bleeding site. MRI is beneficial for evaluating reversible joint changes for earlier intervention in persons with hemophilia A and B.

Treatment & Management

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Media Gallery

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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Author

Lucas Barreira Angelim, MD Resident Physician, Department of Internal Medicine, Einstein Medical Center Philadelphia

Disclosure: Nothing to disclose.

Coauthor(s)

Claudia Mattos da Costa Dourado, MD Clinical Assistant Professor of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University; Associate Program Director, Hematology and Medical Oncology Fellowship Program, Attending Physician, Division of Hematology and Medical Oncology, Department of Medicine, Einstein Medical Center Philadelphia

Claudia Mattos da Costa Dourado, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

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, MBBCh, FRCPC, DTM&H Professor of Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

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

Disclosure: Nothing to disclose.

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 Heart Association, American Society for Biochemistry and Molecular Biology, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, 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.

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.

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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