Factor V Deficiency

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Factor V is an essential component in the blood coagulation cascade. Inherited or acquired deficiencies in factor V are rare causes of bleeding disorders. ^{[1, 2]}

Factor V deficiency is also known as Owren disease. 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 also been called parahemophilia, since hemarthrosis can occur with severe deficiencies and with increased bleeding time. ^{[3, 4]}

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. ^{[5, 6]} Thrombin cleaves fibrinogen to form fibrin, leading to the ultimate step in coagulation, the formation of a fibrin clot. ^[7] See images below.

Inherited factor V deficiency is a rare autosomal recessive disorder that is associated with an abnormal factor V plasma level. Numerous mutations in the F5 gene have been identified in these patients. ^{[5, 8, 9, 10, 11]}  

Anothe rare autosomal recessive disorder, combined factor V and factor VIII deficiency, results from  mutations in either LMAN1 (lectin mannose binding–1) or MCFD2  (multiple coagulation factor deficiency gene 2). Alterations in the proteins encoded by those two genes interfere with efficient secretion of factors V and FVIII. ^[12]

Acquired factor V deficiency is a rare clinical condition in which the development of antibodies to factor V (factor V inhibitors) leads to 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, use of bovine thrombin or medications, and in patients with autoimmune diseases and certain neoplasms. ^{[13, 14]}

Factor V Leiden is a completely different inherited disorder that involves a single point mutation in the factor V gene. Factor V activity levels in patients with factor V Leiden are normal. ^[15] Proteolytic inactivation of factor Va and factor VIIIa by activated protein C (APC) normally limits clot formation; however, factor V Leiden resists inactivation by APC. Consequently, individuals who are homozygous for factor V Leiden have a high incidence of thrombosis. For more information, see Hereditary and Acquired Hypercoagulability.

International

Fewer than 200 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. ^[8] 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. ^[8] 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. ^[8] 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.

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

No apparent racial predilection for factor V deficiency exists. Factor V deficiency affects males and females with equal frequency.

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

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Quek JKS, Wong WH, Tan CW, Tha MH, Nagarajan C, Lee LH, et al. Acquired factor V deficiency in a patient with myeloma and amyloidosis. Thromb Res. 2018 Apr. 164:1-3. [Medline].

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Ni Ainle F, Preston RJ, Jenkins PV, et al. Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation. Blood. 2009 Aug 20. 114(8):1658-65. [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. 2009 Sep. 15(5):1143-53. [Medline].

Liu HC, Shen MC, Eng HL, Wang CH, Lin TM. Asp68His mutation in the A1 domain of human factor V causes impaired secretion and ineffective translocation. Haemophilia. 2014 Jul. 20(4):e318-26. [Medline].

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Wang X, Qin X, Yu Y, Wang R, Liu X, Ji M, et al. Acquired factor V deficiency in a patient with a urinary tract infection presenting with haematuria followed by multiple haemorrhages with an extremely low level of factor V inhibitor: a case report and review of the literature. Blood Coagul Fibrinolysis. 2017 Jun. 28 (4):334-341. [Medline]. [Full Text].

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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. 2005 Jan. 11(1):26-30. [Medline].

Totan M, Albayrak D. Intracranial haemorrhage due to factor V deficiency. Acta Paediatr. 1999 Mar. 88(3):342-3. [Medline].

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Satoh H, Yamashita YT, Ohtsuka M, Sekizawa K, Hasegawa Y. Pulmonary hemorrhage in factor V deficiency. Can Respir J. 1999 Jul-Aug. 6(4):320. [Medline].

Bulato C, Novembrino C, Anzoletti MB, Spiezia L, Gavasso S, Berbenni C, et al. “In vitro” correction of the severe factor V deficiency-related coagulopathy by a novel plasma-derived factor V concentrate. Haemophilia. 2018 Jul. 24 (4):648-656. [Medline].

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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. 2009 Jun 2. [Medline].

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.

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, MD is a member of the following medical societies: Massachusetts Medical Society

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: 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.

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.

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.

Factor V Deficiency

Research & References of Factor V Deficiency|A&C Accounting And Tax Services
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