Journal of Thrombosis and Thrombolysis

, Volume 47, Issue 1, pp 129–133 | Cite as

Combined use of antifibrinolytics and activated prothrombin complex concentrate (aPCC) is not related to thromboembolic events in patients with acquired haemophilia A: data from FAIR Registry

  • S. PascaEmail author
  • C. Ambaglio
  • A. Rocino
  • C. Santoro
  • I. Cantori
  • E. Zanon
  • for the FAIR Study Group


Antifibrinolytics combined with aPCC are not routinely administered to patients with acquired hemophilia A due to increased thrombotic risk. This association normalizes clot stability, and improves the efficacy of therapy, but can increase the risk of severe side effects. Due to these premises it has always raised doubts and perplexities in the clinics. We now report the data of the “FEIBA® on acquired haemophilia A Italian Registry (FAIR Registry)”, a retrospective-prospective study that included 56 patients. This is the first study that assessed the clinical response of the combination of aPCC and antifibrinolytic agents in patients with acquired haemophilia A. A total of 101 acute bleeds were treated with aPCC. Antifibrinolytic agents were used in the treatment of 39.6% of total bleeds, based on both, a clinical assessment and an evaluation of bleeding. Twenty-five of the 30 patients (57.1%) treated with antifibrinolytic drugs showed serious co-morbidity. Among them, 40% presented severe cardiovascular diseases. All bleeds treated with combined therapy had a shorter duration of treatment (mean reduction 16.3%). All the treated patients presented a good tolerability and no arterial or venous thromboembolic events were reported. In our retrospective registry the combination of antifibrinolytics and aPCC appears safe and effective in the treatment of patients with AHA, especially in the case of severe and life-threatening bleeding, but this hypothesis needs to be confirmed in adequate, larger clinical trials.


Acquired haemophilia A Activated prothrombin complex concentrate Antifibrinolytics Thromboembolic risk 



All of the authors meet the International Committee of Medical Journal Editors criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval of the version to be published. The FAIR Study Group: Siragusa S and Napolitano M (Hematology Department, Center of Hemorrhagic and Thrombotic Diseases, University of Palermo); Federici AB (Hematology and Transfusion Medicine Departement, Luigi Sacco Hospital, Milan); Mameli L (Center of Coagulation Diseases, SS Annunziata Hospital, Sassari); Giuffrida G (Hemathology Department, VE Ferrarotto and S.Bambino University Hospital, Catania); Falanga A (Transfusion Medicine and Immunohematology Department, Giovanni XXIII Hospital, Bergamo); Lodigiani C (Medicine Department, Humanitas Clinical Institute, Rozzano); Santoro RC (Center of Hemorrhagic and Thrombotic Diseases, Pugliese-Ciaccio Hospital, Catanzaro).


This work did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. This medical and statistical writing assistance for the FAIR registry was supported by Baxalta-Shire.

Compliance with ethical standards

Conflict of interest

All authors have read and understood JTT policy on declaration of interests and declare that they have no competing interests.

Ethical approval

All procedures performed in this study involving human partecipants were in accordance with the ethical standards of the institutional and/or national research and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

All patients enrolled in our retrospective-prospective registry accepted to participate in the study signing the informed consent as requested by Ethical Committees. In the case of retrospective patients who had died before the start of collection data the informed consent was signed by a family member.


  1. 1.
    Kessler CM, Knobl P (2015) Acquired haemophilia: an overview for clinical practice. Eur J Haematol 95(Suppl 81):36–44CrossRefGoogle Scholar
  2. 2.
    Franchini M, Mannucci PM (2013) Acquired haemophilia A: a 2013 update. Thromb Haemost 110:1114–1120CrossRefGoogle Scholar
  3. 3.
    Kruse-Jarres R, Kempton CL, Baudo F et al (2017) Acquired hemophilia A: updated review of evidence and treatment guidance. Am J Hematol 92(7):695–705CrossRefGoogle Scholar
  4. 4.
    Knoebl P, Marco P, Baudo F, EACH2 Registry Contributors, et al (2012) Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). J Thromb Haemost 10:622–631CrossRefGoogle Scholar
  5. 5.
    Holmström M, Tran HT, Holme PA (2012) Combined treatment with aPCC (FEIBA®) and tranexamic acid in patients with haemophilia A with inhibitors and in patient with acquired haemophilia A—a two-centre experience. Haemophilia 18(4):544–549CrossRefGoogle Scholar
  6. 6.
    Tran HT, Sørensen B, Rea CJ et al (2014) Tranexamic acid as adjunct therapy to bypassing agents in haemophilia A patients with inhibitors. Haemophilia 20(3):369–375CrossRefGoogle Scholar
  7. 7.
    Windyga J, Stefanska-Windyga E, Odnoczko E et al (2016) Activated prothrombin complex concentrate in combination with tranexamic acid: a single centre experience for the treatment of mucosal bleeding and dental extraction in haemophilia patients with inhibitors. Haemophilia 22(5):e465–e468CrossRefGoogle Scholar
  8. 8.
    Schulman S, Kearon C (2005) Subcommittee on control of anticoagulation of the scientific and standardization committee of the international society on thrombosis and haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 3:692–694CrossRefGoogle Scholar
  9. 9.
    Turecek PL, Váradi K, Gritsch T et al (2004) FEIBA®: mode of action. Haemophilia 10(Suppl. 2):3–9CrossRefGoogle Scholar
  10. 10.
    Borg JY, Négrier C, Durieu I, FEIBHAC Study Group, et al (2015) FEIBA in the treatment of acquired haemophilia A: results from the prospective multicentre French ‘FEIBA dans l’hémophilie A acquise’ (FEIBHAC) registry. Haemophilia 21(3):330–337CrossRefGoogle Scholar
  11. 11.
    Zanon E, Milan M, Sarolo L et al (2018) Cerebrovascular diseases in haemophiliacs: a real but understimated risk. Haemophilia 24(1):e3–e5CrossRefGoogle Scholar
  12. 12.
    Humphries TJ, Rule B, Ogbonnaya A et al (2018) Cardiovascular comorbidities in a United States patient population with hemophilia A: a comprehensive chart review. Adv Med Sci 18(2):329–333 63)CrossRefGoogle Scholar
  13. 13.
    Berger K, Schopohl D, Lowe G et al (2016) How to compare cardiovascular disease and risk factors in elderly patients with haemophilia with the general population. Haemophilia 22(5):e406–e416CrossRefGoogle Scholar
  14. 14.
    Minuk L, Jackson S, Iorio A et al (2015) Cardiovascular disease (CVD) in Canadians with haemophilia: age-related CVD in Haemophilia Epidemiological Research (ARCHER study). Haemophilia 21(6):736–741CrossRefGoogle Scholar
  15. 15.
    Valentino LA, Holme PA (2015) Should anti-inhibitor coagulant complex and tranexamic acid be used concomitantly? Haemophilia 21:709–714CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Haemophilia CentreUniversity Hospital of PaduaPaduaItaly
  2. 2.Haemophilia CentreS.Matteo Hospital of PaviaPaviaItaly
  3. 3.Haemophilia and Thrombosis CentreS.Giovanni Bosco Hospital of NeaplesNaplesItaly
  4. 4.Cellular Biotecnology and Haematology DepartmentUmberto I University Hospital of RomeRomeItaly
  5. 5.Centre of Coagulation DiseasesHospital of MacerataMacerataItaly

Personalised recommendations