Thromb Haemost 2022; 122(06): 905-912
DOI: 10.1055/a-1642-4067
Coagulation and Fibrinolysis

New Inhibitors in the Ageing Population: A Retrospective, Observational, Cohort Study of New Inhibitors in Older People with Hemophilia

1   Department for Translational Medicine, Skane University Hospital, Lund University, Malmö, Sweden
Cihan Ay
2   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University Vienna, Vienna, Austria
Manuela Carvalho
3   Department of Immunohemotherapy, Centro Hospitalar de Sao Joao, Porto, Portugal
Roseline D'Oiron
4   Centre pour Hémophiles, Hopital Bicetre-APHP, Cedex, France
Philippe De Moerloose
5   Hopitaux Universitaires de Geneve, Satigny, Geneva, Switzerland
Gerard Dolan
6   Centre for Haemostasis and Thrombosis, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom of Great Britain and Northern Ireland
7   Haemostasis Unit and Laboratory, University Hospitals of Geneva, Geneva, Switzerland
Cedric Hermans
8   Haemostasis and Thrombosis Unit, Division of Haematology, Saint-Luc University Hospital, Brussels, Belgium
Pål Andre Holme
9   Department of Haematology, Institute of Clinical Medicine, Oslo Universit Hospital, Rikshospitalet, Oslo, Norway
Olga Katsarou
10   Department of Hematology, Laiko University Hospital, Athens, Attica, Greece
Gili Kenet
11   National Hemophilia Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
12   Sackler Faculty of Medicine, The Amalia Biron Thrombosis Research Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel
Robert Klamroth
13   Department of Angiology and Coagulation Disorders, Vivantes Klinikum im Friedrichshain, Berlin, Germany
14   Hemophilia and Thrombosis Center, Fondazione Ospedale Maggiore Policlinico, Milan, Italy
15   Center for Thrombosis and Hemorrhagic Diseases, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
Natascha Marquardt
16   Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany
Ramiro Núñez
17   Hemophilia Unit, Hospital Universitario Virgen del Rocio, Sevilla, Andalucía, Spain
Ingrid Pabinger
18   Department of Haematology and Haemostaseology, Allgemeines Krankenhaus (AKH) - Innere Medizin, Wien, Austria
Robert Tait
19   Haemophilia and Thrombosis Centre, Royal Infirmary Glasgow, Glasgow, Strathclyde, United Kingdom of Great Britain and Northern Ireland
20   Van Creveldkliniek, UMC Utrecht, Utrecht, The Netherlands
› Author Affiliations


Introduction A second peak of inhibitors has been reported in patients with severe hemophilia A (HA) aged >50 years in the United Kingdom. The reason for this suggested breakdown of tolerance in the aging population is unclear, as is the potential impact of regular exposure to the deficient factor by prophylaxis at higher age. No data on hemophilia B (HB) have ever been reported.

Aim The ADVANCE Working Group investigated the incidence of late-onset inhibitors and the use of prophylaxis in patients with HA and HB aged ≥40 years.

Methods A retrospective, observational, cohort, survey-based study of all patients aged ≥40 years with HA or HB treated at an ADVANCE hemophilia treatment center.

Results Information on 3,095 people aged ≥40 years with HA or HB was collected. Of the 2,562 patients with severe HA, the majority (73% across all age groups) received prophylaxis. In patients with severe HA, the inhibitor incidence per 1,000 treatment years was 2.37 (age 40–49), 1.25 (age 50–59), and 1.45 (age 60 + ). Overall, the inhibitor incidence was greatest in those with moderate HA (5.77 [age 40–49], 6.59 [age 50–59], and 4.69 [age 60 + ]) and the majority of inhibitor cases were preceded by a potential immune system challenge. No inhibitors in patients with HB were reported.

Conclusion Our data do not identify a second peak of inhibitor development in older patients with hemophilia. Prophylaxis may be beneficial in older patients with severe, and possibly moderate HA, to retain a tolerant state at a higher age.

Publication History

Received: 27 April 2021

Accepted: 09 September 2021

Accepted Manuscript online:
10 September 2021

Article published online:
05 November 2021

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