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Thromb Haemost 1999; 82(04): 1207-1214
DOI: 10.1055/s-0037-1614361
Review Article
Schattauer GmbH

Rare Coagulation Disorders

Flora Peyvandi
1   From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and the Fondazione Luigi Villa, Department of Internal Medicine, IRCCS Maggiore Hospital and University of Milano, Italy; and the Hemophilia Center and Hemostasis Unit, Department of Hematology, Royal Free Hospital and University College London School of Medicine, Royal Free Campus, London, UK
,
P. M. Mannucci
1   From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and the Fondazione Luigi Villa, Department of Internal Medicine, IRCCS Maggiore Hospital and University of Milano, Italy; and the Hemophilia Center and Hemostasis Unit, Department of Hematology, Royal Free Hospital and University College London School of Medicine, Royal Free Campus, London, UK
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Further Information

Publication History

Received 22 April 1999

Accepted after revision 07 July 1999

Publication Date:
08 December 2017 (online)

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Summary

The type of hemorrhagic manifestations that occur in patients with recessively transmitted coagulation disorders and their optimal treatment are not well established as for hemophilia A and B and von Willebrand disease, due to the rarity of these disorders. In a Muslim country like Iran where consanguineous marriages are frequent these disorders are less rare. We chose to evaluate the pattern of bleeding symptoms in 237 Iranian patients with the inherited deficiencies of fibrinogen, factor II, combined factor V and factor VIII, factor V, factor VII and factor X. Considering “severe” life-endangering hemorrhages such as those in the CNS, gastrointestinal tract and from the umbilical cord and those potentially handicapping such as hematomas and hemarthroses; and “mild” epistaxis, menorrhagia, hematuria, oral and postsurgical bleeding, it would appear the most severe diseases are factor X and factor II deficiencies. For the remaining defects only a minority of patients, even those with unmeasurable plasma levels, had life-endangering hemorrhages or muscoloskeletal disabilities as a consequence of hemarthroses and hematomas. The relatively mild severity of clinical manifestations in recessive coagulation disorders commands safety as the primary criterion in the choice of replacement material for treatment. Hence, virally inactivated plasma and factor concentrates should be the products of choice.

Keywords

Inherited coagulation disorders - afibrinogenemia - factor II - factor V - factor VII - factor X
 

  • References

  • 1 Tuddenham EGD, Cooper DN. The molecular genetics of hemostasis and its inherited disorders. Oxford University Press; 1994
    Search in Google Scholar
  • 2 Girolami A, De Marco L, Dal Bo Zanon R, Patrassi G, Cappellato MG. Rare quantitative and qualitative abnormalities of coagulation. Clin Haematol 1985; 14: 385-411.
    PubMedSearch in Google Scholar
  • 3 Shoa’i I, Ala F, Forouzanfar N. Hemophilia in Iran. In: Haemophilia. Ala F, Denson KWE. eds. Excerpta Medica; 1973: XII-XV.
    Search in Google Scholar
  • 4 Peyvandi F, Mannucci PM, Jenkins PV, Lee A, Pasi KJ, Coppola R, Perry DL. Molecular characterization of 22 families with factor VII deficiency. Blood 1998; 92 (Suppl. 01) 711a.
    PubMedSearch in Google Scholar
  • 5 Neerman-Arbez M, Johnson KM, Morris MA, McVey JH, Peyvandi F, Nichols WC, Ginsburg D, Rossier C, Antonarakis SE, Tuddenham EGD. Molecular analysis of the ERGIC-53 gene in 35 families with combined factor V-factor VIII deficiency (F5F8D). Blood 1999; 93: 2253-60.
    PubMedSearch in Google Scholar
  • 6 Akhavan S, Lak M, Mancuso G, Baudo F, Rocino A, Mazzucconi MG, Perkins SJ, Mannucci PM. Molecular characterization of 11 kindreds with prothrombin deficiency. Thromb Haemost 1999; 82 (Suppl.-Abstracts) 17 (abstr. no. 50).
    PubMedSearch in Google Scholar
  • 7 Duga S, Asselta R, Simonic T, Santagostino E, Mannucci PM, Malcovati M, Tenchini ML. First identification of a missense mutation in the D-domain of the fibrinogen beta chain in a case of congenital afibrinogenemia. Thromb Haemost 1999; 82 (Suppl.-Abstracts) 18 (abstr. no. 52).
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Roberts HR, Hoffman M. Other clotting factor deficiencies. In: Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 4th edition. Colman RW, Hirsh J, Marder VJ, Salzman EW. eds. J. B. Lippincott Company; Philadelphia: 1999. in press.
    Search in Google Scholar
  • 9 Roberts HR, Bingham MD. Other coagulation factor deficiencies. In: Thrombosis and Hemorrhage. 2nd edition. Loscalzo J, Schafer AL. eds. Williams and Wilkins; Baltimore: 1998: 773-802.
    Search in Google Scholar
  • 10 Mariani G, Mazzucconi MG. Factor VII congenital deficiency: clinical picture and classification of the variants. Haemostasis 1983; 13: 169-74.
    PubMedSearch in Google Scholar
  • 11 Neerman-Arbez M, Honsberg A, Antonorakis SE, Morris MA. Deletion of the fibrinogen alpha chain gene (FGA) causes congenital afibrinogenemia. J Clin Invest 1999; 103: 215-8.
    CrossrefPubMedSearch in Google Scholar
  • 12 Martinez J. Congenital dysfibrinogenemia. Curr Opin Hematol 1997; 4: 357-65.
    CrossrefPubMedSearch in Google Scholar
  • 13 Suh TT, Holmback K, Jensen NJ, Daugherty CC, Small K, Simon DI, Potter S, Degen JL. Resolution of spontaneous bleeding events but failure of pregnancy in fibrinogen deficient mice. Genes Dev 1995; 15: 2020-33.
    PubMedSearch in Google Scholar
  • 14 Goodwin TM. Congenital hypofibrinogenemia in pregnancy. Obstet Gynecol Surv 1989; 44: 157-61.
    CrossrefPubMedSearch in Google Scholar
  • 15 Al-Mondhiry H, Ehmann WC. Congenital afibrinogenemia. Am J Hematol 1994; 46: 343-7.
    CrossrefPubMedSearch in Google Scholar
  • 16 Montgomery R, Natelson SE. Afibrinogenemia with intracerebral hematoma. Report in a successfully treated case. Am J Dis Child 1977; 131: 555-6.
    PubMedSearch in Google Scholar
  • 17 Fried K, Kaufman S. Congenital afibrinogenemia in 10 offspring of uncle-niece marriages. Clin Genet 1980; 18: 223-7.
    PubMedSearch in Google Scholar
  • 18 Klein HG, Dodd RY, Dzik WH, Luban NL, Ness PM, Pisciotto P, Schiff PD, Snyder EL. Current status of solvent/detergent treated frozen plasma. Transfusion 1998; 38: 102-7.
    CrossrefPubMedSearch in Google Scholar
  • 19 Mannucci PM. The choice of plasma derived clotting factor concentrates. In: Balliere’s Clinical Haematology. Haemophilia Lee C.A.. editor 1996; 9: 272-90.
    PubMedSearch in Google Scholar
  • 20 Lambrecht B, Mohr H, Knouwerhoft J, Schmitt H. Photoinactivation of viruses in human fresh plasma by phenothiazine dyes in combination with visible light. Vox Sang 1991; 60: 207-13.
    CrossrefPubMedSearch in Google Scholar
  • 21 Sun WY, Witte DP, Degen JL, Colbert MC, Holmback K, Xiao Q, Bugge TH, Degen SJ. Prothrombin deficiency results in embryonic and neonatal lethality in mice. Proc. Natl Acad Sci USA 1998; 95: 7597-8002.
    CrossrefPubMedSearch in Google Scholar
  • 22 Chiu HC, Whitaker E, Colman RW. Heterogeneity of human factor V deficiency. Evidence for the existence of an antigen-positive variant. J Clin Invest 1983; 72: 493-503.
    CrossrefPubMedSearch in Google Scholar
  • 23 Tracy PB, Eide LL, Bowie EJ, Mann KG. Radioimmunoassay of factor V in human plasma and platelets. Blood 1982; 60: 59-63.
    PubMedSearch in Google Scholar
  • 24 Murray JM, Rand MD, Egan JO, Murphy S, Kim HC, Mann KG. Factor VNew Brunswick: Ala221-to Val substitution results in reduced cofactor activity. Blood 1995; 86: 1820-7.
    PubMedSearch in Google Scholar
  • 25 Lunghi B, Castoldi E, Mingozzi F, Bernardi F. A novel factor V null mutation detected in a thrombophilic patient with pseudo-homozygous APC resistance and in an asymptomatic unrelated subject. Blood 1998; 92: 1463-4.
    PubMedSearch in Google Scholar
  • 26 Zehender JL, Hiraki D, Jones C, Gross N, Grumet FC. Familial coagulation factor V deficiency caused by a novel 4 base pair insertion in the factor V gene. Thromb Haemost. 1999 in press.
    PubMedSearch in Google Scholar
  • 27 Guasch JF, Cannegieter S, Reitsma PH, Van’t Veer-Korthof ET, Bertina RM. Severe coagulation factor V deficiency caused by a 4 bp deletion in the factor V gene. Br J Haematol 1998; 101: 32-9.
    CrossrefPubMedSearch in Google Scholar
  • 28 Cui J, O’Shea KS, Purkayastha A, Saunders TL, Ginsburg D. Fatal hemorrhage and incomplete block of embryogenesis in mice lacking coagulation factor V. Nature 1996; 384: 66-8.
    CrossrefPubMedSearch in Google Scholar
  • 29 Yang TL, Cui J, Taylor JM, Yang A, Gimber SB, Ginsburg D. Rescue of fatal neonatal hemorrhage in factor V deficient mice by low transgene expression. Thromb Haemost. 1999 in press.
    PubMedSearch in Google Scholar
  • 30 Lak M, Sharifian R, Peyvandi F, Mannucci PM. Symptoms of inherited factor V deficiency in 25 Iranian patients. Br J Haematol 1998; 103: 1067-9.
    CrossrefPubMedSearch in Google Scholar
  • 31 Triplett DA, Brandt JT, Batard MA, Dixon JL, Fair DS. Hereditary factor VII deficiency heterogeneity defined by combined functional and immunochemical analysis. Blood 1985; 66: 1284-7.
    PubMedSearch in Google Scholar
  • 32 Cooper DN, Millar DS, Wacey A, Banner DW, Tuddenham EGD. Inherited factor VII deficiency: molecular genetics and pathophysiology. Thromb Haemost 1997; 78: 151-60.
    Thieme ConnectPubMedSearch in Google Scholar
  • 33 Rosen ED, Chan JC, Idusogie E, Clotman F, Vlasuk G, Luther T, Jalbert LR, Albrecht S, Zhong L, Lissens A, Schoonjans L, Moons L, Collen D, Castellino FJ, Carmeliet P. Mice lacking factor VII develop normally but suffer fatal perinatal bleeding. Nature 1997; 390: 290-4.
    CrossrefPubMedSearch in Google Scholar
  • 34 Marder VJ, Shulman NR. Clinical aspects of congenital factor VII deficiency. Blut 1979; 30: 119-25.
    PubMedSearch in Google Scholar
  • 35 Gershwin ME, Gude JK. Deep vein thrombosis and pulmonary embolism in congenital factor VII deficiency. N Engl J Med 1973; 288: 141-2.
    CrossrefPubMedSearch in Google Scholar
  • 36 Ragni MV, Lewis JH, Spero JA, Hasiba U. Factor VII deficiency. Am J Hematol 1981; 10: 79-88.
    CrossrefPubMedSearch in Google Scholar
  • 37 Hedner U, Glazer S, Falch J. Recombinant activated factor VII in the treatment of bleeding episodes in individuals with inherited and acquired bleeding disorders. Transfusion Med Rev 1993; 7: 78-83.
    CrossrefPubMedSearch in Google Scholar
  • 38 Sadler J. Combined factors V and VIII deficiency climbs onto the map. J Clin Invest 1997; 99: 555-6.
    CrossrefPubMedSearch in Google Scholar
  • 39 Nichols WC, Seligsohn U, Zivelin A, Terry VH, Hertel CE, Wheatley MA, Moussali MJ, Hauri HP, Ciavarella N, Kaufman RJ, Ginsburg D. Mutations in the gene for ERGIC-53, a protein of the endoplasmic reticulum/Golgi intermediate compartment cause combined deficiency of coagulation factors V and VIII. Cell 1998; 93: 61-4.
    CrossrefPubMedSearch in Google Scholar
  • 40 Giddings JC, Seligsohn U, Bloom AL. Immunological studies in combined factor V and factor VIII deficiency. Br J Haematol 1977; 37: 257.
    CrossrefPubMedSearch in Google Scholar
  • 41 Soff GA, Levin J. Familial multiple coagulation factor deficiency. Sem Thromb Haemostas 1981; 7: 112-48.
    PubMedSearch in Google Scholar
  • 42 Peyvandi F, Tuddenham EGD, Akhtari M, Lak M, Mannucci PM. Bleeding symptoms in 27 Iranian patients with factor V and VIII combined deficiency. Br J Haematol 1998; 100: 773-6.
    CrossrefPubMedSearch in Google Scholar
  • 43 Seligsohn U, Zivelin A, Zweang E. Combined factor V and factor VIII deficiency among non-Ashkenazi Jews. New Engl J Med 1982; 307: 1191-3.
    CrossrefPubMedSearch in Google Scholar
  • 44 Perry DJ. Factor X and its deficiency states. Haemophilia 1997; 3: 159-72.
    CrossrefPubMedSearch in Google Scholar
  • 45 Cooper DN, Millar DS, Wacey A, Pemberton S, Tuddenham EGD. Inherited factor X deficiency: molecular genetics and pathophysiology. Thromb Haemost 1997; 78: 161-72.
    Thieme ConnectPubMedSearch in Google Scholar
  • 46 Rosen ED, Liang Z, Cooper A, Dewerchin M, Carmeliet P, Collen D, Castellino FJ. Generation and characterization of factor X deficient mice. Blood 1998; 92 (Suppl. 01) 473a.
    PubMedSearch in Google Scholar
  • 47 Peyvandi F, Mannucci PM, Lak M, Abdoullahi M, Zeinali S, Sharifian R, Perry DJ. Congenital factor X deficiency: spectrum of bleeding symptoms in 32 Iranian patients. Br J Haematol 1998; 102: 626-8.
    CrossrefPubMedSearch in Google Scholar