Advertisement

Multiple Coagulation Factor Deficiency

  • Maryam Sadat Hosseini
  • Mahmood Shams
  • Akbar Dorgalaleh
  • Hassan Mansouritorghabeh
Chapter

Abstract

Bleeding disorders with low plasma activity of more than one coagulation factor have been described in several conditions. Multiple coagulation factor deficiency (MCFD) commonly represents as part of acquired conditions. The most well-known acquired causes are liver disease and disseminated intravascular coagulation (DIC) in which impaired synthesis or excessive consumption of coagulation factors occurs, respectively. Dilution states such as massive transfusion and cardiopulmonary bypass are also considered as conditions which lead to MCFD. Congenital deficiencies of more than one coagulation factor rarely have been also described. Such disorders can be rare autosomal bleeding disorder with extremely low incidence. Congenital MCFD may arise from coinheritance of isolated factor defects or may be a result of a single genetic defect. The latter which comprises most of cases is generally caused by defect of a single gene that is implicated in the process or production/activation of multiple factors. The best examples include combined FV and FVIII deficiency (F5F8D) and vitamin K-dependent coagulation factors (VKDCF) deficiency, which have been thoroughly characterized. Isolated combined coagulation factor deficiencies are extremely rare disorders and restricted to isolated case reports.

Keywords

Combined FV and FVIII deficiency Vitamin K-dependent coagulation factor deficiency Multiple coagulation factor deficiencies Rare bleeding disorders 

References

  1. 1.
    Seligsohn U, Zivelin A, Zwang E. Combined factor V and factor VIII deficiency among non-Ashkenazi Jews. N Engl J Med. 1982;307(19):1191.CrossRefPubMedGoogle Scholar
  2. 2.
    Castaman G, Linari S. Diagnosis and treatment of von Willebrand disease and rare bleeding disorders. J Clin Med. 2017;6(4):45.CrossRefPubMedCentralGoogle Scholar
  3. 3.
    Peyvandi F, Tuddenham E, Akhtari A, Lak M, Mannucci P. Bleeding symptoms in 27 Iranian patients with the combined deficiency of factor V and factor VIII. Br J Haematol. 1998;100(4):733–4.CrossRefGoogle Scholar
  4. 4.
    Zhang B. Recent developments in the understanding of the combined deficiency of FV and FVIII. Br J Haematol. 2009;145(1):15–23.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Mumford AD, Ackroyd S, Alikhan R, Bowles L, Chowdary P, Grainger J, et al. Guideline for the diagnosis and management of the rare coagulation disorders. Br J Haematol. 2014;167(3):304–26.CrossRefPubMedGoogle Scholar
  6. 6.
    Zhang B, Ginsburg D. Familial multiple coagulation factor deficiencies: new biologic insight from rare genetic bleeding disorders. J Thromb Haemost. 2004;2(9):1564–72.CrossRefPubMedGoogle Scholar
  7. 7.
    Zheng C, Liu H-H, Yuan S, Zhou J, Zhang B. Molecular basis of LMAN1 in coordinating LMAN1-MCFD2 cargo receptor formation and ER-to-Golgi transport of FV/FVIII. Blood. 2010;116(25):5698–706.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Zheng C, Liu H-H, Zhou J, Zhang B. EF-hand domains of MCFD2 mediate interactions with both LMAN1 and coagulation factor V or VIII. Blood. 2010;115(5):1081–7.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Oeri J, Matter M, Isenschmid H, Hauser F, Koller F. Congenital factor V deficiency (parahemophilia) with true hemophilia in two brothers. Bibl Paediatr. 1954;58:575.PubMedGoogle Scholar
  10. 10.
    Jin D-Y, Ingram BO, Stafford DW, Tie J-K. Molecular basis of the first reported clinical case of congenital combined deficiency of coagulation factors. Blood. 2017;130(7):948–51.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Nichols WC, Seligsohn U, Zivelin A, Terry VH, Arnold ND, Siemieniak DR, et al. Linkage of combined factors V and VIII deficiency to chromosome 18q by homozygosity mapping. J Clin Investig. 1997;99(4):596.CrossRefPubMedGoogle Scholar
  12. 12.
    Nichols WC, Seligsohn U, Zivelin A, Terry VH, Hertel CE, Wheatley MA, et al. Mutations in the ER–Golgi intermediate compartment protein ERGIC-53 cause combined deficiency of coagulation factors V and VIII. Cell. 1998;93(1):61–70.CrossRefPubMedGoogle Scholar
  13. 13.
    Shetty S, Madkaikar M, Nair S, Pawar A, Baindur S, Pathare A, et al. Combined factor V and VIII deficiency in Indian population. Haemophilia. 2000;6:504–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Mansouritorgabeh H, Rezaieyazdi Z, Pourfathollah A, Rezai J, Esamaili H. Haemorrhagic symptoms in patients with combined factors V and VIII deficiency in North-Eastern Iran. Haemophilia. 2004;10(3):271–5.CrossRefPubMedGoogle Scholar
  15. 15.
    Viswabandya A, Baidya S, Nair SC, Lakshmi KM, Mathews V, George B, 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(7):538–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Zheng C, Zhang B. Combined deficiency of coagulation factors V and VIII: an update. Semin Thromb Hemost. 2013;39(6):613–20.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Karimi M, Cairo A, Safarpour MM, Haghpanah S, Ekramzadeh M, Afrasiabi A, et al. Genotype and phenotype report on patients with combined deficiency of factor V and factor VIII in Iran. Blood Coagul Fibrinolysis. 2014;25(4):360–3.CrossRefPubMedGoogle Scholar
  18. 18.
    Hejer E, Adnen L, Asma J, Ibtihel M, Benammar-Elgaaied A, Gouider E. Identification of a novel mutation in the MCFD2 gene in a Tunisian family with combined factor V and VIII deficiency. Tunis Med. 2012;90(4):343–4.PubMedGoogle Scholar
  19. 19.
    Wang A, Liu X, Wu J, Cai X, Zhu W, Sun Z. Combined FV and FVIII deficiency (F5F8D) in a Chinese family with a novel missense mutation in MCFD2 gene. Haemophilia. 2014;20(6):e436–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Genotypes of patients with combined factor V and VIII deficiency [internet]. 2011. https://c.ymcdn.com/sites/www.isth.org/resource/resmgr/publications/fv_and_viii_mutations-2011.pdf.
  21. 21.
    Wang A, Duan Q, Ding K, Liu X, Wu J, Sun Z. Successful abdominal operation without replacement therapy in a patient with combined factor V (FV) and FVIII deficiency due to novel homozygous mutation in LMAN1. Haemophilia. 2015;21(6):e492–4.CrossRefPubMedGoogle Scholar
  22. 22.
    Elmahmoudi H, Wigren E, Laatiri A, Jlizi A, Elgaaied A, Gouider E, et al. Analysis of newly detected mutations in the MCFD2 gene giving rise to combined deficiency of coagulation factors V and VIII. Haemophilia. 2011;17(5):e923–7.PubMedGoogle Scholar
  23. 23.
    Zhang B, Spreafico M, Zheng C, Yang A, Platzer P, Callaghan MU, et al. Genotype-phenotype correlation in combined deficiency of factor V and factor VIII. Blood. 2008;111(12):5592–600.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Khoriaty R, Vasievich MP, Ginsburg D. The COPII pathway and hematologic disease. Blood. 2012;120(1):31–8.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Latif A, Aledort L. Inherited combined factor deficiency states. In: Hemostasis and thrombosis. Oxford: Wiley; 2014. p. 127–36.CrossRefGoogle Scholar
  26. 26.
    Mansouritorghabeh H, Shirdel A. Desmopressin acetate as a haemostatic elevator in individuals with combined deficiency of factors V and VIII: a clinical trial. J Thromb Haemost. 2016;14(2):336–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Peyvandi F, Menegatti M. Treatment of rare factor deficiencies in 2016. Hematology Am Soc Hematol Educ Program. 2016;2016(1):663–9.PubMedGoogle Scholar
  28. 28.
    Oukkache B, El Graoui O, Zafad S. Combined factor V and VIII deficiency and pregnancy. Int J Hematol. 2012;96(6):786–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Brenner B, Kuperman AA, Watzka M, Oldenburg J. Vitamin K-dependent coagulation factors deficiency. Semin Thromb Hemost. 2009;35(4):439–46.CrossRefPubMedGoogle Scholar
  30. 30.
    Napolitano M, Mariani G, Lapecorella M. Hereditary combined deficiency of the vitamin K-dependent clotting factors. Orphanet J Rare Dis. 2010;5(1):21.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Stafford D. The vitamin K cycle. J Thromb Haemost. 2005;3(8):1873–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Tie JK, Stafford DW. Structural and functional insights into enzymes of the vitamin K cycle. J Thromb Haemost. 2016;14(2):236–47.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Oldenburg J, Marinova M, Müller-Reible C, Watzka M. The vitamin K cycle. Vitam Horm. 2008;78:35–62.CrossRefPubMedGoogle Scholar
  34. 34.
    Oldenburg J, Bevans CG, Müller CR, Watzka M. Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle. Antioxid Redox Signal. 2006;8(3-4):347–53.CrossRefPubMedGoogle Scholar
  35. 35.
    Gallieni M, Fusaro M. Vitamin K and cardiovascular calcification in CKD: is patient supplementation on the horizon? Kidney Int. 2014;86(2):232.CrossRefPubMedGoogle Scholar
  36. 36.
    McMillan CW, Roberts HR. Congenital combined deficiency of coagulation factors II, VII, IX and X: report of a case. N Engl J Med. 1966;274(23):1313–5.CrossRefPubMedGoogle Scholar
  37. 37.
    Chung K-S, Bezeaud A, Goldsmith JC, McMillan CW, Menache D, Roberts HR. Congenital deficiency of blood clotting factors II, VII, IX, and X. Blood. 1979;53(4):776–87.PubMedGoogle Scholar
  38. 38.
    Oldenburg J, Von Brederlow B, Fregin A, Rost S, Wolz W, Eberl W, 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(6):937–41.PubMedGoogle Scholar
  39. 39.
    Brenner B, Sánchez-Vega B, Wu S-M, Lanir N, Stafford DW, Solera J. A missense mutation in γ-glutamyl carboxylase gene causes combined deficiency of all vitamin K-dependent blood coagulation factors. Blood. 1998;92(12):4554–9.PubMedGoogle Scholar
  40. 40.
    Spronk HM, Farah RA, Buchanan GR, Vermeer C, Soute BA. Novel mutation in the γ-glutamyl carboxylase gene resulting in congenital combined deficiency of all vitamin K–dependent blood coagulation factors. Blood. 2000;96(10):3650–2.PubMedGoogle Scholar
  41. 41.
    Lunghi B, Redaelli R, Caimi T, Corno A, Bernardi F, Marchetti G. Novel phenotype and γ-glutamyl carboxylase mutations in combined deficiency of vitamin K-dependent coagulation factors. Haemophilia. 2011;17(5):822–4.PubMedGoogle Scholar
  42. 42.
    Hauschka PV, Lian JB, Cole D, Gundberg CM. Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev. 1989;69(3):990–1047.CrossRefPubMedGoogle Scholar
  43. 43.
    Pauli R, Lian J, Mosher D, Suttie J. Association of congenital deficiency of multiple vitamin K-dependent coagulation factors and the phenotype of the warfarin embryopathy: clues to the mechanism of teratogenicity of coumarin derivatives. Am J Hum Genet. 1987;41(4):566.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Vanakker OM, Martin L, Gheduzzi D, Leroy BP, Loeys BL, Guerci VI, et al. Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity. J Investig Dermatol. 2007;127(3):581–7.CrossRefPubMedGoogle Scholar
  45. 45.
    Palla R, Peyvandi F, Shapiro AD. Rare bleeding disorders: diagnosis and treatment. Blood. 2015;125(13):2052–61.CrossRefPubMedGoogle Scholar
  46. 46.
    Thomas A, Stirling D. Four factor deficiency. Blood Coagul Fibrinolysis. 2003;14:S55–S7.CrossRefPubMedGoogle Scholar
  47. 47.
    Prisco D, Ciuti G, Falciani M. Hemostatic changes in normal pregnancy. Haematol Rep. 2009;1:1–5.CrossRefGoogle Scholar
  48. 48.
    Tartaglia M, Gelb BD, Zenker M. Noonan syndrome and clinically related disorders. Best Pract Res Clin Endocrinol Metab. 2011;25(1):161–79.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. 2013;381(9863):333–42.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Briggs BJ, Dickerman JD. Bleeding disorders in Noonan syndrome. Pediatr Blood Cancer. 2012;58(2):167–72.CrossRefPubMedGoogle Scholar
  51. 51.
    Kurosawa H, Suzumura H, Okuya M, Fukushima K, Sugita K, Fujiwara T, et al. Haemostatic management of surgery for imperforate anus in a patient with 13q deletion syndrome with combined deficiency of factors VII and X. Haemophilia. 2009;15(1):398–400.CrossRefPubMedGoogle Scholar
  52. 52.
    Pfeiffer R, Ott R, Gilgenkrantz S, Alexandre P. Deficiency of coagulation factors VII and X associated with deletion of a chromosome 13 (q34). Evidence from two cases with 46, XY, t (13; Y)(q11; q34). Hum Genet. 1982;62(4):358–60.CrossRefPubMedGoogle Scholar
  53. 53.
    Chilcott J, Russell G, Mumford A. Combined deficiency of factors VII and X: clinical description of two cases and management of spinal surgery. Haemophilia. 2006;12(5):555–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Maryam Sadat Hosseini
    • 1
  • Mahmood Shams
    • 2
    • 3
  • Akbar Dorgalaleh
    • 3
  • Hassan Mansouritorghabeh
    • 4
  1. 1.Department of Hematology and Blood transfusionSchool of Allied Medicine, Shahid Beheshti University of Medical SciencesTehranIran
  2. 2.Department of Laboratory Sciences, Paramedical FacultyBabol University of Medical SciencesBabolIran
  3. 3.Department of Hematology and Blood transfusionSchool of Allied Medicine, Iran University of Medical SciencesTehranIran
  4. 4.Allergy Research CenterSchool of Medicine, Mashhad University of Medical SciencesMashhadIran

Personalised recommendations