Download PDF
Thromb Haemost 2013; 109(02): 238-247
DOI: 10.1160/TH12-07-0476
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Replacement therapy for bleeding episodes in factor VII deficiency

A prospective evaluation
Guglielmo Mariani
1   University of Ferrara, Medical School, Ferrara, Italy
,
Mariasanta Napolitano
2   University of Palermo, Haematology, Palermo, Italy
,
Alberto Dolce
3   National Institute of Statistics, Rome, Italy
,
Rosario Perez Garrido
4   Hospital General Unidad de Haemofilia Virgen del Rocio, Seville, Spain
,
Angelika Batorova
5   The National Haemophilia Centre, Institute of Haematology and Blood Transfusion, University Hospital, Bratislava, Slovakia
,
Mehran Karimi
3   National Institute of Statistics, Rome, Italy
,
Helen Platokouki
7   St. Sophia Children’s Hospital, Haemophilia-Haemostasis Unit, Athens, Greece
,
Günter Auerswald
8   Department of Paediatrics, Central Hospital, Bremen, Germany
,
Anne-Marie Bertrand
9   CRTH de Besançon, Besançon, France
,
Giovanni Di Minno
10   Centro di riferimento regionale Emocoagulopatie, Università Federico II, Naples, Italy
,
Jean F. Schved
11   Hemophilia Centre, CHU Montpellier, France
,
Jens Bjerre
12   Medical and Science Haematology, Novo Nordisk A/S, Bagsvaerd, Denmark
,
Jorgen Ingerslev
13   Centre for Haemophilia and Thrombosis, Aarhus University Hospital, Skejby, Aarhus, Denmark
,
Benny Sørensen
14   Haemostasis and Thrombosis Centre, Guy’s & St Thomas’ Hospital, London, UK
,
Arlette Ruiz-Saez
15   Centro Nacional de Haemofilia, Banco Municipal de Sangre, Caracas, Venezuela
,
the Seven Treatment Evaluation Registry (STER) and the International Factor VII Deficiency Study Groups › Author Affiliations Financial support: Financial support for the study was granted by a number of sources (industry [Novo Nordisk], charities [L’Aquila-AIL Onlus], institutional [University of L’Aquila]) through the Department of Medicine and Public Health of the University of L’Aquila.
Further Information

Publication History

Received: 09 July 2012

Accepted after minor revision: 09 November 2012

Publication Date:
29 November 2017 (online)

    Permissions and Reprints

Summary

Patients with inherited factor VII (FVII) deficiency display different clinical phenotypes requiring ad hoc management. This study evaluated treatments for spontaneous and traumatic bleeding using data from the Seven Treatment Evaluation Registry (STER). One-hundred one bleeds were analysed in 75 patients (41 females; FVII coagulant activity <1–20%). Bleeds were grouped as haemarthroses (n=30), muscle/subcutaneous haematomas (n=16), epistaxis (n=12), gum bleeding (n=13), menorrhagia (n=16), central nervous system (CNS; n=9), gastrointestinal (GI; n=2) and other (n=3). Of 93 evaluable episodes, 76 were treated with recombinant, activated FVII (rFVIIa), eight with fresh frozen plasma (FFP), seven with plasma-derived FVII (pdFVII) and two with prothrombin-complex concentrates. One-day replacement therapy resulted in very favourable outcomes in haemarthroses, and was successful in muscle/subcutaneous haematomas, epistaxis and gum bleeding. For menorrhagia, single- or multiple-dose schedules led to favourable outcomes. No thrombosis occurred; two inhibitors were detected in two repeatedly treated patients (one postrFVIIa, one post-pdFVII). In FVII deficiency, most bleeds were successfully treated with single ‘intermediate’ doses (median 60 µg/kg) of rFVIIa. For the most severe bleeds (CNS, GI) short- or long-term prophylaxis may be optimal.

Keywords

Bleeds - replacement therapy - factor VII deficiency
 

  • References

  • 1 Mannucci PM, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood 2004; 104: 1243-1252.
    CrossrefPubMedGoogle Scholar
  • 2 Mariani G, Bernardi F. Factor VII deficiency. Semin Thromb Hemost 2009; 35: 400-406.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Mariani G, Dolce A. Congenital factor VII deficiency. In: Textbook of Hemophilia. Wiley-Blackwell: 2010. pp. 341-347.
    CrossrefGoogle Scholar
  • 4 Perry DJ. Factor VII Deficiency. Br J Haematol 2002; 118: 689-700.
    CrossrefPubMedGoogle Scholar
  • 5 Borhany M, Pahore Z, Ul Qadr Z. et al. Bleeding disorders in the tribe: result of consanguineous in breeding. Orphanet J Rare Dis 2010; 05: 23.
    CrossrefPubMedGoogle Scholar
  • 6 Bernardi F, Dolce A, Pinotti M. et al. Major differences in bleeding symptoms between factor VII deficiency and hemophilia B. J Thromb Haemost 2009; 07: 774-779.
    CrossrefPubMedGoogle Scholar
  • 7 Mariani G, Herrmann FH, Dolce A. et al. Clinical phenotypes and factor VII genotype in congenital factor VII deficiency. Thromb Haemost 2005; 93: 481-487.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Mariani G, Testa MG, Di Paolantonio T. et al. Use of recombinant, activated factor VII in the treatment of congenital factor VII deficiencies. Vox Sang 1999; 77: 131-136.
    CrossrefPubMedGoogle Scholar
  • 9 Mariani G, Konkle BA, Ingerslev J. Congenital factor VII deficiency: therapy with recombinant activated factor VII -- a critical appraisal. Haemophilia 2006; 12: 19-27.
    CrossrefPubMedGoogle Scholar
  • 10 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: 340-346.
    CrossrefPubMedGoogle Scholar
  • 11 Mariani G, Dolce A, Napolitano M. et al. Invasive procedures and minor surgery in factor VII deficiency. Haemophilia 2012; 18: e63-e65.
    CrossrefPubMedGoogle Scholar
  • 12 Ingerslev J, Christiansen K, Sorensen B. Inhibitor to factor VII in severe factor VII deficiency: detection and course of the inhibitory response. J Thromb Haemost 2005; 03: 799-800.
    CrossrefPubMedGoogle Scholar
  • 13 Kessler C, Mariani G. Clinical manifestations and therapy of the hemophilias. In: Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Lippincott Williams & Wilkins; 2006
    Google Scholar
  • 14 Aledort LM, Haschmeyer RH, Pettersson H. A longitudinal study of orthopaedic outcomes for severe factor-VIII-deficient haemophiliacs. The Orthopaedic Outcome Study Group. J Intern Med 1994; 236: 391-399.
    CrossrefPubMedGoogle Scholar
  • 15 Hallberg L, Hulthen L, Bengtsson C. et al. Iron balance in menstruating women. Eur J Clin Nutr 1995; 49: 200-207.
    PubMedGoogle Scholar
  • 16 Ragni MV, Lewis JH, Spero JA. et al. Factor VII deficiency. Am J Hematol 1981; 10: 79-88.
    CrossrefPubMedGoogle Scholar
  • 17 Morfini M, Martinowitz U, Batorova A. et al. Pharmacokinetics of FVII. Blood. 2011 118. Abstract E2259
    PubMedGoogle Scholar