Factor V

http://emedicine.medscape.com/article/209492-overview

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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 deficiency is a rare inherited coagulopathy. Factor V deficiency 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 fifth 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 V deficiency 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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Factor V

http://emedicine.medscape.com/article/209492-overview

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 Hoffman and 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 fibrin, leading to the ultimate step in coagulation, the formation of a fibrin 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 novel sequence 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 deficiency varies from bruising to lethal hemorrhage.

Race
No apparent racial predilection for factor V deficiency exists.

Sex
Factor V deficiency affects males and females with equal frequency.

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

Contributor Information and Disclosures

Author Olga 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 Disclosure: Nothing to disclose. 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 Disclosure: Nothing to disclose. Specialty Editor Board 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 Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences Disclosure: Nothing to disclose. 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 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, 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 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 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 Editor Emmanuel 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 Disclosure: Nothing to disclose.

References
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