eMedicine Specialties > Hematology > Coagulation, Hemostasis, and Disorders

Factor VII: Differential Diagnoses & Workup

Author: Jeyanthi Ramanarayanan, MD, Attending Physician, Department of Medicine, Division of Hematology and Medical Oncology, Stratton Veterans Affairs Medical Center
Coauthor(s): Ganapathy S Krishnan, MBBS, Fellow, Department of Hematology and Oncology, Michigan State University; Francisco J Hernandez-Ilizaliturri, MD, Assistant Professor, Departments of Medicine and Immunology, Roswell Park Cancer Institute, State University of New York at Buffalo
Contributor Information and Disclosures

Updated: Feb 14, 2008

Differential Diagnoses

Vitamin K Deficiency

Other Problems to Be Considered

  • Liver disease
  • Oral anticoagulation (eg, with warfarin)
  • Factor X deficiency and some variants of factor IX deficiency: Patients with these conditions may also occasionally exhibit prolonged PTs. In contrast to factor VII deficiency, the activated partial thromboplastin time (aPTT) is also prolonged.
  • Familial multiple factor deficiency type III: Inherited combined deficiency of prothrombin and factors VII, IX, and X has been reported. Levels of factor VII in this syndrome are lower than those in disorders with other vitamin K-dependent factors.
  • Factor V deficiency and lupus anticoagulants: These should be also considered in the differential for a prolonged PT.
  • Combined deficiency of factors VII and X: This has also been reported to occur, albeit rarely.
  • Liver disease, vitamin K deficiency, and oral coagulant-induced conditions: These conditions can be differentiated from factor VII deficiency by measuring other vitamin K-dependent factor levels, which are also decreased. These 3 conditions are associated with isolated prolongation of the PT, which is later followed by a prolonged aPTT.

Workup

Laboratory Studies

  • Routine initial hemostatic tests include an aPTT, a PT, and a 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, 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.

More on Factor VII

Overview: Factor VII
Differential Diagnoses & Workup: Factor VII
Treatment & Medication: Factor VII
Follow-up: Factor VII
Multimedia: Factor VII
References
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References

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Further Reading

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Keywords

FVII, F7 gene, proconvertin, stable factor, serum prothrombin conversion accelerator, SPCA, autoprothrombin I, recombinant factor VIIa, rFVIIa, NovoSeven, coagulation, procoagulants, coagulation cascade, anticoagulant factors, Dubin-Johnson syndrome, Rotor syndrome, prothrombin conversion accelerator deficiency, coagulation disorder, blood disorder blood disease, hemophilia A, hemophilia, hemophilia B

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Contributor Information and Disclosures

Author

Jeyanthi Ramanarayanan, MD, Attending Physician, Department of Medicine, Division of Hematology and Medical Oncology, Stratton Veterans Affairs Medical Center
Jeyanthi Ramanarayanan, MD is a member of the following medical societies: American Association of Physicians of Indian Origin, American Society of Clinical Oncology, and American Society of Hematology
Disclosure: Nothing to disclose.

Coauthor(s)

Ganapathy S Krishnan, MBBS, Fellow, Department of Hematology and Oncology, Michigan State University
Disclosure: Nothing to disclose.

Francisco J Hernandez-Ilizaliturri, MD, Assistant Professor, Departments of Medicine and Immunology, Roswell Park Cancer Institute, State University of New York at Buffalo
Francisco J Hernandez-Ilizaliturri, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Clinical Oncology, and American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Drexel University College of Medicine
Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Ronald A Sacher, MB, BCh, MD, FRCPC, Director of the Hoxworth Blood Center, Professor, Departments of Internal Medicine and Pathology, University of Cincinnati Medical Center
Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Society of Hematology
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Roche Honoraria Consulting

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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