Factor V Deficiency

Rosanna Asselta; Flora Peyvandi

doi:10.1055/s-0029-1225760

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2009; 35(4): 382-389
DOI: 10.1055/s-0029-1225760

Factor V Deficiency

Rosanna Asselta¹ , Flora Peyvandi²

¹Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy
²A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, University of Milan and Luigi Villa Foundation, Milan, Italy

Abstract

ABSTRACT

Congenital factor V (FV) deficiency is a bleeding disorder associated with mild to severe hemorrhagic symptoms and a prevalence in the general population of 1 in 1,000,000 in the homozygous form. Patients with FV deficiency and clinically significant manifestations (mainly involving mucosal tracts) show very low or unmeasurable plasma FV levels and are usually homozygous or compound heterozygous for mutations located in the FV gene (F5). Heterozygous carriers have approximately half-normal levels of FV and are usually asymptomatic. Replacement therapy for FV-deficient patients can only rely on administration of fresh-frozen plasma because specific FV concentrates are unavailable and FV is not present in cryoprecipitate or prothrombin complex concentrates. A total of 56 mutations have been published to date as being responsible for severe or moderately severe FV deficiency; more than two thirds of these are null mutations (mainly decreasing FV expression), with the remaining being missense mutations (usually impairing FV secretion). This article will provide a concise description of the FV protein and gene and will review the molecular, clinical, and therapeutic aspects of FV deficiency.

KEYWORDS

Factor V - factor V deficiency - mutational spectrum - clinical manifestations - treatment

Volltext

Referenzen

REFERENCES

1 Mann K G, Kalafatis M. Factor V: a combination of Dr Jekyll and Mr Hyde. Blood. 2003; 101 20-30
2 Stormorken H. The discovery of factor V: a tricky clotting factor. J Thromb Haemost. 2003; 1 206-213
3 Mannucci P M, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood. 2004; 104 1243-1252
4 Lak M, Sharifian R, Peyvandi F, Mannucci P M. Symptoms of inherited factor V deficiency in 35 Iranian patients. Br J Haematol. 1998; 103 1067-1069
5 Acharya S S, Coughlin A, Dimichele D M. North American Rare Bleeding Disorder Study Group . Rare Bleeding Disorder Registry: deficiencies of factors II, V, VII, X, XIII, fibrinogen and dysfibrinogenemias. J Thromb Haemost. 2004; 2 248-256
6 Zhang B, Spreafico M, Zheng C et al.. Genotype-phenotype correlation in combined deficiency of factor V and factor VIII. Blood. 2008; 111 5592-5600
7 Kent W J, Sugnet C W, Furey T S et al.. The human genome browser at UCSC. Genome Res. 2002; 12 996-1006
8 Chiu H C, Schick P K, Colman R W. Biosynthesis of factor V in isolated guinea pig megakaryocytes. J Clin Invest. 1985; 75 339-346
9 Gewirtz A M, Keefer M, Doshi K, Annamalai A E, Chiu H C, Colman R W. Biology of human megakaryocyte factor V. Blood. 1986; 67 1639-1648
10 Giampaolo A, Vulcano F, Macioce G et al.. Factor-V expression in platelets from human megakaryocytic culture. Br J Haematol. 2005; 128 108-111
11 Sun H, Yang T L, Yang A, Wang X, Ginsburg D. The murine platelet and plasma factor V pools are biosynthetically distinct and sufficient for minimal hemostasis. Blood. 2003; 102 2856-2861
12 Dall'Osso C, Guella I, Duga S et al.. Molecular characterization of three novel splicing mutations causing factor V deficiency and analysis of the F5 gene splicing pattern. Haematologica. 2008; 93 1505-1513
13 Frischmeyer P A, Dietz H C. Nonsense-mediated mRNA decay in health and disease. Hum Mol Genet. 1999; 8 1893-1900
14 Lejeune F, Maquat L E. Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells. Curr Opin Cell Biol. 2005; 17 309-315
15 Jenny R J, Pittman D D, Toole J J et al.. Complete cDNA and derived amino acid sequence of human factor V. Proc Natl Acad Sci U S A. 1987; 84 4846-4850
16 Cripe L D, Moore K D, Kane W H. Structure of the gene for human coagulation factor V. Biochemistry. 1992; 31 3777-3785
17 Nicolaes G A, Dahlbäck B. Factor V and thrombotic disease: description of a janus-faced protein. Arterioscler Thromb Vasc Biol. 2002; 22 530-538
18 Xue J, Kalafatis M, Mann K G. Determination of the disulfide bridges in factor Va light chain. Biochemistry. 1993; 32 5917-5923
19 Xue J, Kalafatis M, Silveira J R, Kung C, Mann K G. Determination of the disulfide bridges in factor Va heavy chain. Biochemistry. 1994; 33 13109-13116
20 Kumar H PM, Besman M J, Lundblad R L, Jenny N S, Mann K G. Carbohydrate analysis of plasma factor V and factor VIII. Thromb Haemost. 1999; (Suppl 82) 102a
21 Macedo-Ribeiro S, Bode W, Huber R et al.. Crystal structures of the membrane-binding C2 domain of human coagulation factor V. Nature. 1999; 402 434-439
22 Adams T E, Hockin M F, Mann K G, Everse S J. The crystal structure of activated protein C-inactivated bovine factor Va: implications for cofactor function. Proc Natl Acad Sci U S A. 2004; 101 8918-8923
23 Stoilova-McPhie S, Parmenter C D, Segers K, Villoutreix B O, Nicolaes G A. Defining the structure of membrane-bound human blood coagulation factor Va. J Thromb Haemost. 2008; 6 76-82
24 Lee C J, Lin P, Chandrasekaran V et al.. Proposed structural models of human factor Va and prothrombinase. J Thromb Haemost. 2008; 6 83-89
25 Asselta R, Tenchini M L, Duga S. Inherited defects of coagulation factor V: the hemorrhagic side. J Thromb Haemost. 2006; 4 26-34
26 Lunghi B, Scanavini D, Castoldi E et al.. The factor V Glu1608Lys mutation is recurrent in familial thrombophilia. J Thromb Haemost. 2005; 3 2032-2038
27 Schrijver I, Hong D W, Mandle L et al.. High frequency of premature termination mutations in the factor V gene: three factor V deficiency case reports and a mutation review. Thromb Haemost. 2005; 93 610-611
28 Asselta R, Dall'Osso C, Duga S, Spreafico M, Saxena R, Tenchini M L. Coagulation factor V gene analysis in five Indian patients: identification of three novel small deletions. Haematologica. 2006; 91 1724-1726
29 Kling S J, Griffee M, Flanders M M, Rodgers G M. Factor V deficiency caused by a novel missense mutation, Ile417Thr, in the A2 domain. J Thromb Haemost. 2006; 4 481-483
30 Traynis I, Jones C D, Gibb C B, Acharya S S, Zehnder J L. First molecular characterization of a patient with combined factor V and factor VII deficiency. Thromb Haemost. 2006; 95 1031-1032
31 Yamakage N, Ikejiri M, Okumura K et al.. A case of coagulation factor V deficiency caused by compound heterozygous mutations in the factor V gene. Haemophilia. 2006; 12 172-178
32 Zheng W D, Liu Y H, Liu H F, Chen Z H, Wang Y. [Identification of two novel mutations of human blood coagulation factor V gene in a Chinese family with congenital factor V deficiency]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2006; 23 515-518
33 Cai X H, Wang X F, Ding Q L, Fu Q H, Wang H L. Factor V C1149G and 5609-10INSCGTGGTT causing factor V deficiency: molecular characterization by in-vitro expression. Thromb Haemost. 2007; 98 683-685
34 Caudill J S, Sood R, Zehnder J L, Pruthi R K, Steensma D P. Severe coagulation factor V deficiency associated with an interstitial deletion of chromosome 1q. J Thromb Haemost. 2007; 5 626-628
35 Jones C D, Yeung C, Negro F, Zehnder J L. Molecular characterization and subcellular localization of Tyr478del: a pathogenic in-frame deletion in coagulation factor V. J Thromb Haemost. 2007; 5 431-433
36 Shinozawa K, Amano K, Suzuki T et al.. Molecular characterization of 3 factor V mutations, R2174L, V1813M, and a 5-bp deletion, that cause factor V deficiency. Int J Hematol. 2007; 86 407-413
37 Lunghi B, Pinotti M, Maestri I, Batorova A, Bernardi F. Evaluation of factor V mRNA to define the residual factor V expression levels in severe factor V deficiency. Haematologica. 2008; 93 477-478
38 Song J, Guella I, Kwon K Y et al.. A novel in-frame deletion in the factor V C1 domain associated with severe coagulation factor V deficiency in a Korean family. Blood Coagul Fibrinolysis. 2009; 20 150-156
39 Vos H L. An online database of mutations and polymorphisms in and around the coagulation factor V gene. J Thromb Haemost. 2007; 5 185-188
40 Castoldi E, Lunghi B, Mingozzi F et al.. A missense mutation (Y1702C) in the coagulation factor V gene is a frequent cause of factor V deficiency in the Italian population. Haematologica. 2001; 86 629-633
41 Scanavini D, Girelli D, Lunghi B et al.. Modulation of factor V levels in plasma by polymorphisms in the C2 domain. Arterioscler Thromb Vasc Biol. 2004; 24 200-206
42 Vos H L. Inherited defects of coagulation factor V: the thrombotic side. J Thromb Haemost. 2006; 4 35-40
43 Yamazaki T, Nicolaes G A, Sørensen K W, Dahlbäck B. Molecular basis of quantitative factor V deficiency associated with factor V R2 haplotype. Blood. 2002; 100 2515-2521
44 Murray J M, Rand M D, Egan J O, Murphy S, Kim H C, Mann K G. Factor V New Brunswick: Ala221-to-Val substitution results in reduced cofactor activity. Blood. 1995; 86 1820-1827
45 Steen M, Miteva M, Villoutreix B O, Yamazaki T, Dahlbäck B, Factor V. Factor V New Brunswick: Ala221Val associated with FV deficiency reproduced in vitro and functionally characterized. Blood. 2003; 102 1316-1322
46 Monaldini L, Asselta R, Malcovati M, Tenchini M L, Duga S. The DNA-pooling technique allowed for the identification of three novel mutations responsible for afibrinogenemia. J Thromb Haemost. 2005; 3 2591-2593
47 Duckers C, Simioni P, Spiezia L et al.. Low plasma levels of tissue factor pathway inhibitor in patients with congenital factor V deficiency. Blood. 2008; 112 3615-3623
48 Adcock D M, Hoefner D M, Kottke-Marchant K, Marlar R A, Szamosi D I, Warunek D J. Collection, Transport, and Processing of Blood Specimens for Testing Plasma-Based Coagulation Assays and Molecular Hemostasis Assays: Approved Guideline, Fifth Edition. Wayne, PA; Clinical Laboratory Standards Institute 2008 CLSI document H21–A5
49 Zürcher M, Sulzer I, Barizzi G, Lämmle B, Alberio L. Stability of coagulation assays performed in plasma from citrated whole blood transported at ambient temperature. Thromb Haemost. 2008; 99 416-426
50 Di Paola J, Nugent D, Young G. Current therapy for rare factor deficiencies. Haemophilia. 2001; 7(Suppl 1) 16-22
51 Bolton-Maggs P H, Perry D J, Chalmers E A et al.. The rare coagulation disorders—review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation. Haemophilia. 2004; 10 593-628
52 Peyvandi F, Duga S, Akhavan S, Mannucci P M. Rare coagulation deficiencies. Haemophilia. 2002; 8 308-321
53 Salooja N, Martin P, Khair K, Liesner R, Hann I. Severe factor V deficiency and neonatal intracranial haemorrhage: a case report. Haemophilia. 2000; 6 44-46
54 Tarantino M D, Ross M P, Daniels T M, Nichols W L. Modulation of an acquired coagulation factor V inhibitor with intravenous immune globulin. J Pediatr Hematol Oncol. 1997; 19 226-231
55 Chediak J, Ashenhurst J B, Garlick I, Desser R K. Successful management of bleeding in a patient with factor V inhibitor by platelet transfusions. Blood. 1980; 56 835-841
56 Salooja N, Martin P, Khair K, Liesner R, Hann I. Severe factor V deficiency and neonatal intracranial haemorrhage: a case report. Haemophilia. 2000; 6 44-46
57 Altisent C, Lozano M, Sol E et al.. Dental extraction using rFVIIa in a patient with severe FV deficiency. Haemophilia. 2000; 6 408
58 Divanon F, Hecquard C, Borel-Derlon A. Experience with use of recombinant activated factor VII. J Clin Pharm Ther. 2002; 27 133-138
59 González-Boullosa R, Ocampo-Martínez R, Alarcón-Martín M J, Suárez-Rodríguez M, Domínguez-Viguera L, González-Fajo G. The use of activated recombinant coagulation factor VII during haemarthroses and synovectomy in a patient with congenital severe factor V deficiency. Haemophilia. 2005; 11 167-170
60 Lee C A, Chi C, Pavord S R UK Haemophilia Centre Doctors' Organization et al. The obstetric and gynaecological management of women with inherited bleeding disorders—review with guidelines produced by a taskforce of UK Haemophilia Centre Doctors' Organization. Haemophilia. 2006; 12 301-336

Dr. Rosanna AsseltaPh.D.

Department of Biology and Genetics for Medical Sciences, University of Milan

Via Viotti 3/5 - 20133 Milan, Italy

eMail: rosanna.asselta@unimi.it