Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Rare inherited coagulation disorders

Pier Mannuccio Mannucci, MD
Section Editor
Lawrence LK Leung, MD
Deputy Editor
Jennifer S Tirnauer, MD


A variety of inherited coagulation disorders are associated with clinical bleeding, including inherited deficiencies of factors XIII (13), XI (11), X (10), VII (7), V (5), and II (2, prothrombin), as well as some rare combined factor deficiencies. These conditions may be referred to as rare (or recessively) inherited coagulation disorders (RICDs); rare coagulation deficiencies (RCDs); rare bleeding disorders (RBDs); or rare congenital bleeding disorders.

This topic review discusses the genetics, diagnosis, and management of inherited deficiencies of factor XIII, X, VII, V, II, and combined deficiencies of factors V and VIII, and vitamin K-dependent factors.

The more common inherited coagulation disorders, such as von Willebrand disease (VWD), hemophilia A and B, factor XI (11) deficiency, and fibrinogen disorders, are discussed in detail in separate topic reviews:

Hemophilia A and B – (See "Clinical manifestations and diagnosis of hemophilia" and "Treatment of hemophilia".)

Von Willebrand disease – (See "Clinical presentation and diagnosis of von Willebrand disease".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Mon Nov 21 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Tagliabue L, Duca F, Peyvandi F. Apparently dominant transmission of a recessive disease: deficiency of factor VII in Iranian Jews. Ann Ital Med Int 2000; 15:263.
  2. Tuddenham EG, Cooper DN. The Molecular Genetics of Haemostasis and Its Inherited Disorders. Oxford, United Kingdom: Oxford Medical Publications; 1994. Oxford Monography on Medical Genetics No. 25.
  3. Peyvandi F, Duga S, Akhavan S, Mannucci PM. Rare coagulation deficiencies. Haemophilia 2002; 8:308.
  4. Mannucci PM, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood 2004; 104:1243.
  5. Neerman-Arbez M, Honsberger A, Antonarakis SE, Morris MA. Deletion of the fibrinogen [correction of fibrogen] alpha-chain gene (FGA) causes congenital afibrogenemia. J Clin Invest 1999; 103:215.
  6. Duga S, Asselta R, Santagostino E, et al. Missense mutations in the human beta fibrinogen gene cause congenital afibrinogenemia by impairing fibrinogen secretion. Blood 2000; 95:1336.
  7. Hunault M, Arbini AA, Carew JA, et al. Characterization of two naturally occurring mutations in the second epidermal growth factor-like domain of factor VII. Blood 1999; 93:1237.
  8. Watzke HH, Wallmark A, Hamaguchi N, et al. Factor XSanto Domingo. Evidence that the severe clinical phenotype arises from a mutation blocking secretion. J Clin Invest 1991; 88:1685.
  9. Zivelin A, Bauduer F, Ducout L, et al. Factor XI deficiency in French Basques is caused predominantly by an ancestral Cys38Arg mutation in the factor XI gene. Blood 2002; 99:2448.
  10. Stenson PD, Ball EV, Mort M, et al. Human Gene Mutation Database (HGMD): 2003 update. Hum Mutat 2003; 21:577.
  11. Kohler HP. Novel treatment for congenital FXIII deficiency. Blood 2012; 119:5060.
  12. Ichinose A. Physiopathology and regulation of factor XIII. Thromb Haemost 2001; 86:57.
  13. Cooper DN, Millar DS, Wacey A, et al. Inherited factor X deficiency: molecular genetics and pathophysiology. Thromb Haemost 1997; 78:161.
  14. Peyvandi F, Menegatti M, Santagostino E, et al. Gene mutations and three-dimensional structural analysis in 13 families with severe factor X deficiency. Br J Haematol 2002; 117:685.
  15. Uprichard J, Perry DJ. Factor X deficiency. Blood Rev 2002; 16:97.
  16. Pinotti M, Camire RM, Baroni M, et al. Impaired prothrombinase activity of factor X Gly381Asp results in severe familial CRM+ FX deficiency. Thromb Haemost 2003; 89:243.
  17. Deam S, Uprichard J, Eaton JT, et al. Factor X Leicester: Ile411Phe associated with a low antigen level and a disproportionately low functional activity of factor X. J Thromb Haemost 2003; 1:603.
  18. Peyvandi F, Jenkins PV, Mannucci PM, et al. Molecular characterisation and three-dimensional structural analysis of mutations in 21 unrelated families with inherited factor VII deficiency. Thromb Haemost 2000; 84:250.
  19. Wulff K, Herrmann FH. Twenty two novel mutations of the factor VII gene in factor VII deficiency. Hum Mutat 2000; 15:489.
  20. Peyvandi F, Carew JA, Perry DJ, et al. Abnormal secretion and function of recombinant human factor VII as the result of modification to a calcium binding site caused by a 15-base pair insertion in the F7 gene. Blood 2001; 97:960.
  21. Cunha ML, Bakhtiari K, Peter J, et al. A novel mutation in the F5 gene (factor V Amsterdam) associated with bleeding independent of factor V procoagulant function. Blood 2015; 125:1822.
  22. Vincent LM, Tran S, Livaja R, et al. Coagulation factor V(A2440G) causes east Texas bleeding disorder via TFPIα. J Clin Invest 2013; 123:3777.
  23. Kuang SQ, Hasham S, Phillips MD, et al. Characterization of a novel autosomal dominant bleeding disorder in a large kindred from east Texas. Blood 2001; 97:1549.
  24. Bertina RM, Koeleman BP, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369:64.
  25. Castaman G, Lunghi B, Missiaglia E, et al. Phenotypic homozygous activated protein C resistance associated with compound heterozygosity for Arg506Gln (factor V Leiden) and His1299Arg substitutions in factor V. Br J Haematol 1997; 99:257.
  26. Akhavan S, Mannucci PM, Lak M, et al. Identification and three-dimensional structural analysis of nine novel mutations in patients with prothrombin deficiency. Thromb Haemost 2000; 84:989.
  27. Akhavan S, De Cristofaro R, Peyvandi F, et al. Molecular and functional characterization of a natural homozygous Arg67His mutation in the prothrombin gene of a patient with a severe procoagulant defect contrasting with a mild hemorrhagic phenotype. Blood 2002; 100:1347.
  28. De Cristofaro R, Akhavan S, Altomare C, et al. A natural prothrombin mutant reveals an unexpected influence of A-chain structure on the activity of human alpha-thrombin. J Biol Chem 2004; 279:13035.
  29. Langdown J, Luddington RJ, Huntington JA, Baglin TP. A hereditary bleeding disorder resulting from a premature stop codon in thrombomodulin (p.Cys537Stop). Blood 2014; 124:1951.
  30. Zhang B, Cunningham MA, Nichols WC, et al. Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex. Nat Genet 2003; 34:220.
  31. Cunningham MA, Pipe SW, Zhang B, et al. LMAN1 is a molecular chaperone for the secretion of coagulation factor VIII. J Thromb Haemost 2003; 1:2360.
  32. Zhang B, McGee B, Yamaoka JS, et al. Combined deficiency of factor V and factor VIII is due to mutations in either LMAN1 or MCFD2. Blood 2006; 107:1903.
  33. Zhang B. Recent developments in the understanding of the combined deficiency of FV and FVIII. Br J Haematol 2009; 145:15.
  34. Brenner B. Hereditary deficiency of vitamin K-dependent coagulation factors. Thromb Haemost 2000; 84:935.
  35. Sadler JE. Medicine: K is for koagulation. Nature 2004; 427:493.
  36. Darghouth D, Hallgren KW, Shtofman RL, et al. Compound heterozygosity of novel missense mutations in the gamma-glutamyl-carboxylase gene causes hereditary combined vitamin K-dependent coagulation factor deficiency. Blood 2006; 108:1925.
  37. Rost S, Fregin A, Ivaskevicius V, et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 2004; 427:537.
  38. Ruiz-Saez A. Occurrence of thrombosis in rare bleeding disorders. Semin Thromb Hemost 2013; 39:684.
  39. Menegatti M, Karimi M, Garagiola I, et al. A rare inherited coagulation disorder: combined homozygous factor VII and factor X deficiency. Am J Hematol 2004; 77:90.
  40. Eid SS, Kamal NR, Shubeilat TS, Wael AG. Inherited bleeding disorders: a 14-year retrospective study. Clin Lab Sci 2008; 21:210.
  41. Acharya SS, Coughlin A, Dimichele DM, 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.
  42. Bolton-Maggs PH. The rare inherited coagulation disorders. Pediatr Blood Cancer 2013; 60 Suppl 1:S37.
  43. Salcioglu Z, Tugcu D, Akcay A, et al. Surgical interventions in childhood rare factor deficiencies: a single-center experience from Turkey. Blood Coagul Fibrinolysis 2013; 24:854.
  44. Fışgın T, Balkan C, Celkan T, et al. Rare coagulation disorders: a retrospective analysis of 156 patients in Turkey. Turk J Haematol 2012; 29:48.
  45. Lak M, Sharifian R, Peyvandi F, Mannucci PM. Symptoms of inherited factor V deficiency in 35 Iranian patients. Br J Haematol 1998; 103:1067.
  46. Peyvandi F, Mannucci PM, Asti D, et al. Clinical manifestations in 28 Italian and Iranian patients with severe factor VII deficiency. Haemophilia 1997; 3:242.
  47. Peyvandi F, Tuddenham EG, Akhtari AM, et al. Bleeding symptoms in 27 Iranian patients with the combined deficiency of factor V and factor VIII. Br J Haematol 1998; 100:773.
  48. Peyvandi F, Mannucci PM, Lak M, et al. Congenital factor X deficiency: spectrum of bleeding symptoms in 32 Iranian patients. Br J Haematol 1998; 102:626.
  49. Peyvandi F, Lak M, Mannucci PM. Factor XI deficiency in Iranians: its clinical manifestations in comparison with those of classic hemophilia. Haematologica 2002; 87:512.
  50. Lak M, Peyvandi F, Ali Sharifian A, et al. Pattern of symptoms in 93 Iranian patients with severe factor XIII deficiency. J Thromb Haemost 2003; 1:1852.
  51. Dargaud Y, de Mazancourt P, Rugeri L, et al. An unusual clinical presentation of factor XIII deficiency and issues relating to the monitoring of factor XIII replacement therapy. Blood Coagul Fibrinolysis 2008; 19:447.
  52. Peyvandi F, Palla R, Menegatti M, et al. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost 2012; 10:615.
  53. Acharya SS. Rare bleeding disorders in children: identification and primary care management. Pediatrics 2013; 132:882.
  54. Romagnolo C, Burati S, Ciaffoni S, et al. Severe factor X deficiency in pregnancy: case report and review of the literature. Haemophilia 2004; 10:665.
  55. Ichinose A, Asahina T, Kobayashi T. Congenital blood coagulation factor XIII deficiency and perinatal management. Curr Drug Targets 2005; 6:541.
  56. Girolami A, Ferrari S, Sambado L, et al. Myocardial infarctions and other acute coronary syndromes in rare congenital bleeding disorders: a critical analysis of all reported cases. Clin Appl Thromb Hemost 2015; 21:359.
  57. van Meegeren ME, de Rooy JW, Schreuder HW, Brons PP. Bone cysts in patients with afibrinogenaemia: a literature review and two new cases. Haemophilia 2014; 20:244.
  58. Andes WA, Beltran G, Stuckey WJ. Pseudotumor in a patient with factor IX deficiency. South Med J 1973; 66:905.
  59. Spena S, Asselta R, Platé M, et al. Pseudo-exon activation caused by a deep-intronic mutation in the fibrinogen gamma-chain gene as a novel mechanism for congenital afibrinogenaemia. Br J Haematol 2007; 139:128.
  60. Guella I, Paraboschi EM, van Schalkwyk WA, et al. Identification of the first Alu-mediated large deletion involving the F5 gene in a compound heterozygous patient with severe factor V deficiency. Thromb Haemost 2011; 106:296.
  61. Giansily-Blaizot M, Thorel D, Khau Van Kien P, et al. Characterisation of a large complex intragenic re-arrangement in the FVII gene (F7) avoiding misdiagnosis in inherited factor VII deficiency. Br J Haematol 2007; 138:359.
  62. Bastida JM, Del Rey M, Lozano ML, et al. Design and application of a 23-gene panel by next-generation sequencing for inherited coagulation bleeding disorders. Haemophilia 2016; 22:590.
  63. http://www.cdc.gov/ncbddd/hemophilia/htc.html (Accessed on October 28, 2014).
  64. Lak M, Keihani M, Elahi F, et al. Bleeding and thrombosis in 55 patients with inherited afibrinogenaemia. Br J Haematol 1999; 107:204.
  65. Di Paola J, Nugent D, Young G. Current therapy for rare factor deficiencies. Haemophilia 2001; 7(suppl 1):16.
  66. Mumford AD, Ackroyd S, Alikhan R, et al. Guideline for the diagnosis and management of the rare coagulation disorders: a United Kingdom Haemophilia Centre Doctors' Organization guideline on behalf of the British Committee for Standards in Haematology. Br J Haematol 2014; 167:304.
  67. https://www.hemophilia.org/Researchers-Healthcare-Providers/Medical-and-Scientific-Advisory-Council-MASAC/All-MASAC-Recommendations/Recommendations-Concerning-Products-Licensed-for-the-Treatment-of-Hemophilia-and-Other-Bleeding-Disorders (Accessed on October 28, 2014).
  68. Siboni SM, Biguzzi E, Pasta G, et al. Management of orthopaedic surgery in rare bleeding disorders. Haemophilia 2014; 20:693.
  69. Konje JC, Murphy P, de Chazal R, et al. Severe factor X deficiency and successful pregnancy. Br J Obstet Gynaecol 1994; 101:910.
  70. Kumar M, Mehta P. Congenital coagulopathies and pregnancy: report of four pregnancies in a factor X-deficient woman. Am J Hematol 1994; 46:241.
  71. http://www1.wfh.org/publication/files/pdf-1227.pdf (Accessed on October 29, 2014).
  72. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468038.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Accessed on October 20, 2015).
  73. http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM468127.pdf (Accessed on October 22, 2015).
  74. http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM197905.pdf (Accessed on October 22, 2014).
  75. Dal Bo Zanon R, Calzavara M, Vicari T, et al. Dental extraction in congenital hemorrhagic patients. Folia Haematol Int Mag Klin Morphol Blutforsch 1986; 113:799.
  76. García-Matte R, María Constanza Beltrán M, Ximena Fonseca A, Pamela Zúñiga C. Management of children with inherited mild bleeding disorders undergoing adenotonsillar procedures. Int J Pediatr Otorhinolaryngol 2012; 76:291.
  77. Kim SH, Park YS, Kwon KH, et al. Surgery in patients with congenital factor VII deficiency: A single center experience. Korean J Hematol 2012; 47:281.
  78. Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other indications. Drugs 1999; 57:1005.
  79. Seitz R, Duckert F, Lopaciuk S, et al. ETRO Working Party on Factor XIII questionnaire on congenital factor XIII deficiency in Europe: status and perspectives. Study Group. Semin Thromb Hemost 1996; 22:415.
  80. https://www.hemophilia.org/Researchers-Healthcare-Providers/Medical-and-Scientific-Advisory-Council-MASAC/All-MASAC-Recommendations/Recommendations-on-Administration-of-Vaccines-to-Individuals-with-Bleeding-Disorders (Accessed on October 28, 2014).
  81. Eshghi P, Abolghasemi H, Sanei-Moghaddam E, et al. Factor XIII deficiency in south-east Iran. Haemophilia 2004; 10:470.
  82. Trinh CH, Sh Elsayed W, Eshghi P, et al. Molecular analysis of sixteen unrelated factor XIIIA deficient families from south-east of Iran. Br J Haematol 2008; 140:581.
  83. Bolton-Maggs PH, Perry DJ, Chalmers EA, et al. The rare coagulation disorders--review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation. Haemophilia 2004; 10:593.
  84. Anwar R, Minford A, Gallivan L, et al. Delayed umbilical bleeding--a presenting feature for factor XIII deficiency: clinical features, genetics, and management. Pediatrics 2002; 109:E32.
  85. Ivaskevicius V, Seitz R, Kohler HP, et al. International registry on factor XIII deficiency: a basis formed mostly on European data. Thromb Haemost 2007; 97:914.
  86. de Jager T, Pericleous L, Kokot-Kierepa M, et al. The burden and management of FXIII deficiency. Haemophilia 2014; 20:733.
  87. Rodeghiero F, Castaman GC, Di Bona E, et al. Successful pregnancy in a woman with congenital factor XIII deficiency treated with substitutive therapy. Report of a second case. Blut 1987; 55:45.
  88. Kobayashi T, Terao T, Kojima T, et al. Congenital factor XIII deficiency with treatment of factor XIII concentrate and normal vaginal delivery. Gynecol Obstet Invest 1990; 29:235.
  89. Naderi M, Eshghi P, Cohan N, et al. Successful delivery in patients with FXIII deficiency receiving prophylaxis: report of 17 cases in Iran. Haemophilia 2012; 18:773.
  90. Sharief LA, Kadir RA. Congenital factor XIII deficiency in women: a systematic review of literature. Haemophilia 2013; 19:e349.
  91. Asahina T, Kobayashi T, Okada Y, et al. Studies on the role of adhesive proteins in maintaining pregnancy. Horm Res 1998; 50 Suppl 2:37.
  92. Asahina T, Kobayashi T, Okada Y, et al. Maternal blood coagulation factor XIII is associated with the development of cytotrophoblastic shell. Placenta 2000; 21:388.
  93. Inbal A, Muszbek L. Coagulation factor deficiencies and pregnancy loss. Semin Thromb Hemost 2003; 29:171.
  94. Snir A, Brenner B, Paz B, et al. The role of fibrin matrices and tissue factor in early-term trophoblast proliferation and spreading. Thromb Res 2013; 132:477.
  95. Gootenberg JE. Factor concentrates for the treatment of factor XIII deficiency. Curr Opin Hematol 1998; 5:372.
  96. Brackmann HH, Egbring R, Ferster A, et al. Pharmacokinetics and tolerability of factor XIII concentrates prepared from human placenta or plasma: a crossover randomised study. Thromb Haemost 1995; 74:622.
  97. Winkelman L, Sims GE, Haddon ME, et al. A pasteurised concentrate of human plasma factor XIII for therapeutic use. Thromb Haemost 1986; 55:402.
  98. Caudill JS, Nichols WL, Plumhoff EA, et al. Comparison of coagulation factor XIII content and concentration in cryoprecipitate and fresh-frozen plasma. Transfusion 2009; 49:765.
  99. Dreyfus M, Barrois D, Borg JY, et al. Successful long-term replacement therapy with FXIII concentrate (Fibrogammin(®) P) for severe congenital factor XIII deficiency: a prospective multicentre study. J Thromb Haemost 2011; 9:1264.
  100. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm379696.htm (Accessed on December 30, 2013).
  101. http://www.cslbehring.com/news-room/Corifact-FDA-Approval (Accessed on October 30, 2014).
  102. Inbal A, Oldenburg J, Carcao M, et al. Recombinant factor XIII: a safe and novel treatment for congenital factor XIII deficiency. Blood 2012; 119:5111.
  103. Janbain M, Nugent DJ, Powell JS, et al. Use of Factor XIII (FXIII) concentrate in patients with congenital FXIII deficiency undergoing surgical procedures. Transfusion 2015; 55:45.
  104. Asahina T, Kobayashi T, Takeuchi K, Kanayama N. Congenital blood coagulation factor XIII deficiency and successful deliveries: a review of the literature. Obstet Gynecol Surv 2007; 62:255.
  105. Naderi M, Dorgalaleh A, Alizadeh S, et al. Clinical manifestations and management of life-threatening bleeding in the largest group of patients with severe factor XIII deficiency. Int J Hematol 2014; 100:443.
  106. Lusher J, Pipe SW, Alexander S, Nugent D. Prophylactic therapy with Fibrogammin P is associated with a decreased incidence of bleeding episodes: a retrospective study. Haemophilia 2010; 16:316.
  107. Kerlin B, Brand B, Inbal A, et al. Pharmacokinetics of recombinant factor XIII at steady state in patients with congenital factor XIII A-subunit deficiency. J Thromb Haemost 2014; 12:2038.
  108. Nugent D. Corifact™/Fibrogammin® P in the prophylactic treatment of hereditary factor XIII deficiency: results of a prospective, multicenter, open-label study. Thromb Res 2012; 130 Suppl 2:S12.
  109. McMahon C, Smith J, Goonan C, et al. The role of primary prophylactic factor replacement therapy in children with severe factor X deficiency. Br J Haematol 2002; 119:789.
  110. Hunault M, Bauer KA. Recombinant factor VIIa for the treatment of congenital factor VII deficiency. Semin Thromb Hemost 2000; 26:401.
  111. Giansily-Blaizot M, Verdier R, Biron-Adréani C, et al. Analysis of biological phenotypes from 42 patients with inherited factor VII deficiency: can biological tests predict the bleeding risk? Haematologica 2004; 89:704.
  112. Barnett JM, Demel KC, Mega AE, et al. Lack of bleeding in patients with severe factor VII deficiency. Am J Hematol 2005; 78:134.
  113. Mariani G, Herrmann FH, Dolce A, et al. Clinical phenotypes and factor VII genotype in congenital factor VII deficiency. Thromb Haemost 2005; 93:481.
  114. McVey JH, Boswell E, Mumford AD, et al. Factor VII deficiency and the FVII mutation database. Hum Mutat 2001; 17:3.
  115. Benlakhal F, Mura T, Schved JF, et al. A retrospective analysis of 157 surgical procedures performed without replacement therapy in 83 unrelated factor VII-deficient patients. J Thromb Haemost 2011; 9:1149.
  116. Herrmann FH, Wulff K, Auerswald G, et al. Factor VII deficiency: clinical manifestation of 717 subjects from Europe and Latin America with mutations in the factor 7 gene. Haemophilia 2009; 15:267.
  117. Ragni MV, Lewis JH, Spero JA, Hasiba U. Factor VII deficiency. Am J Hematol 1981; 10:79.
  118. Brenner B, Wiis J. Experience with recombinant-activated factor VII in 30 patients with congenital factor VII deficiency. Hematology 2007; 12:55.
  119. Mariani G, Dolce A, Batorova A, et al. Recombinant, activated factor VII for surgery in factor VII deficiency: a prospective evaluation - the surgical STER. Br J Haematol 2011; 152:340.
  120. Mariani G, Napolitano M, Dolce A, et al. Replacement therapy for bleeding episodes in factor VII deficiency. A prospective evaluation. Thromb Haemost 2013; 109:238.
  121. Napolitano M, Giansily-Blaizot M, Dolce A, et al. Prophylaxis in congenital factor VII deficiency: indications, efficacy and safety. Results from the Seven Treatment Evaluation Registry (STER). Haematologica 2013; 98:538.
  122. Rosenthal C, Volk T, Spies C, et al. Successful coronary artery bypass graft surgery in severe congenital factor VII deficiency: perioperative treatment with factor VII concentrate. Thromb Haemost 2007; 98:900.
  123. Liu N, Aldea S, François D, et al. Recombinant activated factor VII for a patient with factor VII deficiency undergoing urgent intracerebral haematoma evacuation with underlying cavernous angioma. Br J Anaesth 2009; 103:858.
  124. Zaidi SM, Qureshi RN, Adil SN. Factor VII deficiency and pregnancy: a case report and review of literature. J Pak Med Assoc 2010; 60:136.
  125. Shirasawa H, Yoshioka T, Sawada K, Terada Y. Repeated recombinant activated factor VII administration in a patient with congenital factor VII deficiency undergoing modified radical hysterectomy: a case report. Haemophilia 2014; 20:e101.
  126. Miyata N, Isaka M, Kojima H, et al. Continuous infusion of recombinant activated factor VII for bleeding control after lobectomy in a patient with inherited factor VII deficiency. Gen Thorac Cardiovasc Surg 2016; 64:177.
  127. http://www.novo-pi.com/novosevenrt.pdf (Accessed on November 05, 2014).
  128. Farah R, Al Danaf J, Braiteh N, et al. Life-threatening bleeding in factor VII deficiency: the role of prenatal diagnosis and primary prophylaxis. Br J Haematol 2015; 168:452.
  129. 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.
  130. Duckers C, Simioni P, Rosing J, Castoldi E. Advances in understanding the bleeding diathesis in factor V deficiency. Br J Haematol 2009; 146:17.
  131. Duckers C, Simioni P, Spiezia L, et al. Residual platelet factor V ensures thrombin generation in patients with severe congenital factor V deficiency and mild bleeding symptoms. Blood 2010; 115:879.
  132. Bouchard BA, Chapin J, Brummel-Ziedins KE, et al. Platelets and platelet-derived factor Va confer hemostatic competence in complete factor V deficiency. Blood 2015; 125:3647.
  133. Lee WS, Chong LA, Begum S, et al. Factor V inhibitor in neonatal intracranial hemorrhage secondary to severe congenital factor V deficiency. J Pediatr Hematol Oncol 2001; 23:244.
  134. Ozkaya H, Akcan AB, Aydemir G, et al. Factor v deficiency associated with congenital cardiac disorder and intracranial hemorrage. Indian J Hematol Blood Transfus 2013; 29:99.
  135. Mishra P, Naithani R, Dolai T, et al. Intracranial haemorrhage in patients with congenital haemostatic defects. Haemophilia 2008; 14:952.
  136. Totan M, Albayrak D. Intracranial haemorrhage due to factor V deficiency. Acta Paediatr 1999; 88:342.
  137. Ardillon L, Lefrançois A, Graveleau J, et al. Management of bleeding in severe factor V deficiency with a factor V inhibitor. Vox Sang 2014; 107:97.
  138. Perez Botero J, Burns D, Thompson CA, Pruthi RK. Successful treatment with thalidomide of a patient with congenital factor V deficiency and factor V inhibitor with recurrent gastrointestinal bleeding from small bowel arteriovenous malformations. Haemophilia 2013; 19:e59.
  139. Girolami A, Ruzzon E, Tezza F, et al. Arterial and venous thrombosis in rare congenital bleeding disorders: a critical review. Haemophilia 2006; 12:345.
  140. O'Connell MP, Eogan M, Murphy KM, et al. Solvent-detergent plasma as replacement therapy in a pregnant patient with factor V deficiency. J Matern Fetal Neonatal Med 2004; 16:69.
  141. Doyle S, O'Brien P, Murphy K, et al. Coagulation factor content of solvent/detergent plasma compared with fresh frozen plasma. Blood Coagul Fibrinolysis 2003; 14:283.
  142. Gavva C, Yates SG, Rambally S, Sarode R. Transfusion management of factor V deficiency: three case reports and review of the literature. Transfusion 2016; 56:1745.
  143. Younesi MR, Aligoudarzi SL. Successful delivery in patients with severe congenital factor V deficiency: a study of five homozygous patients. Haemophilia 2013; 19:e318.
  144. Kitamura A, Yamashita H, Okumura T, Asahina I. Extraction of four wisdom teeth in a patient with congenital factor V deficiency hemophilia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011; 112:e1.
  145. Mansouritorgabeh H, Rezaieyazdi Z, Pourfathollah AA, et al. Haemorrhagic symptoms in patients with combined factors V and VIII deficiency in north-eastern Iran. Haemophilia 2004; 10:271.
  146. Viswabandya A, Baidya S, Nair SC, et al. Clinical manifestations of combined factor V and VIII deficiency: a series of 37 cases from a single center in India. Am J Hematol 2010; 85:538.
  147. Chuansumrit A, Mahaphan W, Pintadit P, et al. Combined factor V and factor VIII deficiency with congenital heart disease:response to plasma and DDAVP infusion. Southeast Asian J Trop Med Public Health 1994; 25:217.
  148. Bauduer F, Guichandut JP, Ducout L. Successful use of fresh frozen plasma and desmopressin for transurethral prostatectomy in a French Basque with combined factors V +VIII deficiency. J Thromb Haemost 2004; 2:675.
  149. Chapin J, Cardi D, Gibb C, Laurence J. Combined factor V and factor VIII deficiency: a report of a case, genetic analysis, and response to desmopressin acetate. Clin Adv Hematol Oncol 2012; 10:472.
  150. Lobel JS, Majumdar S, Kovats-Bell S. Successful prophylactic treatment for bleeding in a girl with severe hereditary prothrombin deficiency using a prothrombin complex concentrate (Bebulin VH). J Pediatr Hematol Oncol 2004; 26:480.
  151. Mathias M, Pollard D, Riddell A. Prophylaxis in severe prothrombin deficiency. Br J Haematol 2011; 152:243.
  152. Brenner B, Tavori S, Zivelin A, et al. Hereditary deficiency of all vitamin K-dependent procoagulants and anticoagulants. Br J Haematol 1990; 75:537.
  153. Boneh A, Bar-Ziv J. Hereditary deficiency of vitamin K-dependent coagulation factors with skeletal abnormalities. Am J Med Genet 1996; 65:241.
  154. Oldenburg J, von Brederlow B, Fregin A, et al. Congenital deficiency of vitamin K dependent coagulation factors in two families presents as a genetic defect of the vitamin K-epoxide-reductase-complex. Thromb Haemost 2000; 84:937.
  155. Spronk HM, Farah RA, Buchanan GR, et al. Novel mutation in the gamma-glutamyl carboxylase gene resulting in congenital combined deficiency of all vitamin K-dependent blood coagulation factors. Blood 2000; 96:3650.
  156. Marchetti G, Caruso P, Lunghi B, et al. Vitamin K-induced modification of coagulation phenotype in VKORC1 homozygous deficiency. J Thromb Haemost 2008; 6:797.
  157. Brenner B, Sánchez-Vega B, Wu SM, et al. A missense mutation in gamma-glutamyl carboxylase gene causes combined deficiency of all vitamin K-dependent blood coagulation factors. Blood 1998; 92:4554.
  158. Vicente V, Maia R, Alberca I, et al. Congenital deficiency of vitamin K-dependent coagulation factors and protein C. Thromb Haemost 1984; 51:343.
  159. McMahon MJ, James AH. Combined deficiency of factors II, VII, IX, and X (Borgschulte-Grigsby deficiency) in pregnancy. Obstet Gynecol 2001; 97:808.
  160. http://www.wfh.org/en/page.aspx?pid=662 (Accessed on November 13, 2014).
  161. http://www1.wfh.org/publication/files/pdf-1337.pdf (Accessed on November 13, 2014).
  162. http://www.clotbase.bicnirrh.res.in (Accessed on August 19, 2010).
  163. http://www.rarecoagulationdisorders.org/ (Accessed on December 30, 2013).
  164. Peyvandi F, Spreafico M. National and international registries of rare bleeding disorders. Blood Transfus 2008; 6 Suppl 2:s45.