Factor V

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Factor V

Author: Olga Kozyreva, MD; Chief Editor: Emmanuel C Besa, MD more...

Updated: Jan 10, 2012

Background

Isolated factor V def iciency is a rare inherited coagulopathy. Factor V def iciency is also known as Owren disease or

parahemophilia. Dr. Paul Owren identified this defect in Norway in 1943. Using relatively primitive technology, he was

able to deduce the existence of a f ifth component required for fibrin formation, which he named factor V, thus

beginning the era of Roman numerology for coagulation factors. Dr. Owren's work defined factor V as the activity in

normal plasma that corrected the prothrombin time (PT) of the plasma in a patient with factor V deficiency. Factor Vdeficiency has been called parahemophilia since hemarthrosis can occur with severe deficiencies and with increased

bleeding time.[1, 2]

Pathophysiology

Factor V is an essential component in the blood coagulation cascade. Factor V is synthesized in the liver and possibly

in megakaryocytes. Factor V circulates in an inactive form. During coagulation, factor V is converted to the active

cofactor, factor Va, via limited proteolysis by the serine protease a-thrombin. Factor Va and activated factor Xa form

the prothrombinase complex. The prothrombinase complex is responsible for the rapid conversion of the zymogen

prothrombin to the active serine protease a-thrombin.[3, 4] See images below.

Antithrombin sites of action.

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r V http://emedicine.medscape.com/article/209492-

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Cell surface-directed hemostasis. Initially, a small amount of thrombin is generated on the surface of the tissue factor (TF)–bearing cell.Following amplification, the second burst generates a larger amount of thrombin, leading to fibrin (clot) formation. Adapted from Hoffmanand Monroe, Thromb Haemost 2001, 85(6): 958-65.

Factor V deficiency is a rare condition and is associated with an abnormal factor V plasma level.

Acquired inhibitor against coagulation factor V is a rare clinical condition with hemorrhagic complications of varying

severity. The addition of normal plasma cannot correct the prolonged PT and activated partial thromboplastin time

(aPTT). Factor V inhibitors can occur after surgery, childbirth, autoimmune diseases, and with certain neoplasms.

Thrombin cleaves fibrinogen to form f ibrin, leading to the ultimate step in coagulation, the formation of a f ibrin clot.[5]

Factor V Leiden is a completely different inherited disorder in which factor V is mutated in a specific gene, leading to

hypercoagulable status. The mutation is very common, occurring in 5% of the US population. Factor V activity levels in

patients with factor V Leiden are normal.[6]

Epidemiology

Frequency

International

Only 150 cases of congenital factor V deficiency have been reported worldwide since 1943. Homozygous factor V

deficiency is rare, occurring in approximately 1 per million population.

Delev et al presented 39 German patients with factor V deficiency.[7]

In 36 cases with an identifiable causative

mutation, 20 patients were heterozygous for the mutation, whereas 9 were homozygous, 6 were compound

heterozygous, and 1 proband was pseudohomozygous.[7]

There were no mutations found in the remaining 3 patients.

The investigators identified 33 uniquely different mutations of a total 42 genetic mutations: 19 missense mutations, 8

nonsense mutations, 4 small deletions, and 2 splice site mutations.[7]

Of the 33 unique mutations, 23 were novelsequence variations not previously reported, and all changes found in exon 13 led to null alleles as nonsense

mutations or small deletions.

Mortality/Morbidity

The severity of factor V def iciency varies from bruising to lethal hemorrhage.

Race

No apparent racial predilection for factor V deficiency exists.

Sex

Factor V def iciency affects males and females with equal frequency.

Age

Factor V def iciency affects all ages. The age at presentation indirectly varies with the severity of disease.

Contributor Information and DisclosuresAuthorOlga Kozyreva, MD Attending Physician, Division of Hematology-Oncology, St Elizabeth's Medical Center;

Assistant Professor, Tufts University School of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)Sarah K May, MD Consulting Staff, Department of Hematology-Oncology, Caritas Carney Hospital,


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Commonwealth Hematology-Oncology PC


Karl J D'Silva, MD Assistant Clinical Professor of Medicine, Department of Hematology/Oncology, Lahey Clinic,Sophia Gordon Cancer Center

Karl J D'Silva, MD is a member of the following medical societies: Massachusetts Medical Society


Specialty Editor BoardPaul 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 Heart

Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and NewYork Academy of Sc iences


Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College

of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Ronald A Sacher, MB, BCh, MD, FRCPC Professor, Internal Medicine and Pathology, Director, Hoxworth Blood

Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for

the Advancement of Science, American Association of Blood Banks, American Clinical and ClimatologicalAssociation, American Society for Clinical Pathology, American Society of Hematology, College of American

Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis,

and Royal College of Physicians and Surgeons of Canada

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Rebecca J Schmidt, DO, FACP, FASN Professor of Medicine, Section Chief, Department of Medicine, Section ofNephrology, West Virginia University School of Medicine

Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: 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: Renal Ventures Ownership interest Other

Chief EditorEmmanuel C Besa, MD Professor, Department of Medicine, Division of Hematologic Malignancies and

Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of 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


References

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