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

Jan Astermark; Cihan Ay; Manuela Carvalho; Roseline D'Oiron; Philippe De Moerloose; Gerard Dolan; Pierre Fontana; Cedric Hermans; Pål Andre Holme; Olga Katsarou; Gili Kenet; Robert Klamroth; Maria Elisa Mancuso; Natascha Marquardt; Ramiro Núñez; Ingrid Pabinger; Robert Tait; Paul van der Valk

doi:10.1055/a-1642-4067

Thrombosis and Haemostasis, Table of Contents

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

Jan Astermark

¹Department for Translational Medicine, Skane University Hospital, Lund University, Malmö, Sweden

,

Cihan Ay

²Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University Vienna, Vienna, Austria

,

Manuela Carvalho

³Department of Immunohemotherapy, Centro Hospitalar de Sao Joao, Porto, Portugal

,

Roseline D'Oiron

⁴Centre pour Hémophiles, Hopital Bicetre-APHP, Cedex, France

,

Philippe De Moerloose

⁵Hopitaux Universitaires de Geneve, Satigny, Geneva, Switzerland

,

Gerard Dolan

⁶Centre for Haemostasis and Thrombosis, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom of Great Britain and Northern Ireland

,

Pierre Fontana

⁷Haemostasis Unit and Laboratory, University Hospitals of Geneva, Geneva, Switzerland

,

Cedric Hermans

⁸Haemostasis and Thrombosis Unit, Division of Haematology, Saint-Luc University Hospital, Brussels, Belgium

,

Pål Andre Holme

⁹Department of Haematology, Institute of Clinical Medicine, Oslo Universit Hospital, Rikshospitalet, Oslo, Norway

,

Olga Katsarou

¹⁰Department of Hematology, Laiko University Hospital, Athens, Attica, Greece

,

Gili Kenet

¹¹National Hemophilia Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel

¹²Sackler Faculty of Medicine, The Amalia Biron Thrombosis Research Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel

,

Robert Klamroth

¹³Department of Angiology and Coagulation Disorders, Vivantes Klinikum im Friedrichshain, Berlin, Germany

,

Maria Elisa Mancuso

¹⁴Hemophilia and Thrombosis Center, Fondazione Ospedale Maggiore Policlinico, Milan, Italy

¹⁵Center for Thrombosis and Hemorrhagic Diseases, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy

,

Natascha Marquardt

¹⁶Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany

,

Ramiro Núñez

¹⁷Hemophilia Unit, Hospital Universitario Virgen del Rocio, Sevilla, Andalucía, Spain

,

Ingrid Pabinger

¹⁸Department of Haematology and Haemostaseology, Allgemeines Krankenhaus (AKH) - Innere Medizin, Wien, Austria

,

Robert Tait

¹⁹Haemophilia and Thrombosis Centre, Royal Infirmary Glasgow, Glasgow, Strathclyde, United Kingdom of Great Britain and Northern Ireland

,

Paul van der Valk

²⁰Van Creveldkliniek, UMC Utrecht, Utrecht, The Netherlands

› Author Affiliations

Abstract

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.

Keywords

hemophilia A/B - inhibitors - prophylaxis - aging

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References

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