Factor V

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

Updated: Jan 10, 2012

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Background
Pathophysiology
Epidemiology
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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.

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]

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.

Proceed to Clinical Presentation

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, 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 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, 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

Owren P. Parahaemophilia: haemorrhagic diathesis due to absence of a previously unknown clotting factor. Lancet. 1947;Vol I:446-8.
Duckers C, Simioni P, Rosing J, Castoldi E. Advances in understanding the bleeding diathesis in factor V deficiency. Br J Haematol. Jun 2009;146(1):17-26. [Medline].
Asselta R, Peyvandi F. Factor V deficiency. Semin Thromb Hemost. Jun 2009;35(4):382-9. [Medline].
Cramer TJ, Gale AJ. The anticoagulant function of coagulation factor V. Thromb Haemost. Nov 24 2011;107(1):[Medline].
Ni Ainle F, Preston RJ, Jenkins PV, et al. Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation. Blood. Aug 20 2009;114(8):1658-65. [Medline].
Hamedani AG, Cole JW, Cheng Y, Sparks MJ, O'Connell JR, Stine OC, et al. Factor V Leiden and Ischemic Stroke Risk: The Genetics of Early Onset Stroke (GEOS) Study. J Stroke Cerebrovasc Dis. Nov 17 2011;[Medline].
Delev D, Pavlova A, Heinz S, Seifried E, Oldenburg J. Factor 5 mutation profile in German patients with homozygous and heterozygous factor V deficiency. Haemophilia. Sep 2009;15(5):1143-53. [Medline].
Fu YX, Kaufman R, Rudolph AE, Collum SE, Blinder MA. Multimodality therapy of an acquired factor V inhibitor. Am J Hematol. Apr 1996;51(4):315-8. [Medline].
Spreafico M, Peyvandi F. Combined factor V and factor VIII deficiency. Semin Thromb Hemost. Jun 2009;35(4):390-9. [Medline].
Esmon CT. Basic mechanisms and pathogenesis of venous thrombosis. Blood Rev. Sep 2009;23(5):225-9. [Medline].
Girolami A, Scandellari R, Lombardi AM, Girolami B, Bortoletto E, Zanon E. Pregnancy and oral contraceptives in factor V deficiency: a study of 22 patients (five homozygotes and 17 heterozygotes) and review of the literature. Haemophilia. Jan 2005;11(1):26-30. [Medline].
Ichikawa H. Successful total gastrectomy of gastric cancer in a congenital factor V deficient patient [in Japanese]. Nippon Ronen Igakkai Zasshi. Mar 2000;37(3):245-9. [Medline].
Lak M, Sharifian R, Peyvandi F, Mannucci PM. Symptoms of inherited factor V deficiency in 35 Iranian patients. Br J Haematol. Dec 1998;103(4):1067-9. [Medline].
Lee GR, Foerster J, Greer J, et al, eds. Wintrobe's Clinical Hematology. Vol 2. 10^th ed. Baltimore, Md: Lippincott, Williams & Wilkins; 1999:1710-12.
Mann KG, Kalafatis M. Factor V: a combination of Dr Jekyll and Mr Hyde. Blood. Jan 1 2003;101(1):20-30. [Medline].
Mitterstieler G, Muller W, Geir W. Congenital factor V deficiency. A family study. Scand J Haematol. Jul 1978;21(1):9-13. [Medline].
Nowak-Gottl U, Weiler H, Hernandez I, et al. Fibrinogen alpha and gamma genes and factor VLeiden in children with thromboembolism: results from 2 family-based association studies. Blood. Aug 27 2009;114(9):1947-53. [Medline].
Sacco S, Dragani A, Davi G, Carolei A. Four recurrent intracerebral haemorrhages. Cerebrovasc Dis. 2003;16(4):435-6. [Medline].
Satoh H, Yamashita YT, Ohtsuka M, Sekizawa K, Hasegawa Y. Pulmonary hemorrhage in factor V deficiency. Can Respir J. Jul-Aug 1999;6(4):320. [Medline].
Song JW, Um MR, Ahn HS, Hong CY. A case of congenital factor V deficiency. J Korean Med Sci. Sep 1987;2(3):179-82. [Medline].
Suehisa E, Kawasaki T, Toku M, Hidaka Y. Low level of factor V is associated with development of deep-vein thrombosis in Japanese patients. Thromb Res. Jun 2 2009;[Medline].
Totan M, Albayrak D. Intracranial haemorrhage due to factor V deficiency. Acta Paediatr. Mar 1999;88(3):342-3. [Medline].
Tracy PB, Mann KG. Abnormal formation of the prothrombinase complex: factor V deficiency and related disorders. Hum Pathol. Feb 1987;18(2):162-9. [Medline].
Yokoyama T, Tatemoto Y, Osaki T. Hemostatic treatment after tooth extraction in a patient with factor V deficiency. Oral Dis. Sep 1997;3(3):196-8. [Medline].
Yotsumoto G, Masuda H, Toyokawa K, Iguro Y, Kinjo T, Sakata R. Off-pump coronary artery bypass grafting in a patient with congenital factor V deficiency: report of a case. Surg Today. 2005;35(2):142-4. [Medline].
Zehnder JL, Hiraki DD, Jones CD, Gross N, Grumet FC. Familial coagulation factor V deficiency caused by a novel 4 base pair insertion in the factor V gene: factor V Stanford. Thromb Haemost. Sep 1999;82(3):1097-9. [Medline].