Page 190 - Haematologica3

Correspondence:
c.j.fijnvandraat@amc.uva.nl
Received: September 1, 2017. Accepted: December 27, 2017. Pre-published: January 5, 2018.
doi:10.3324/haematol.2017.180059
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Haematologica 2018 Volume 103(3):550-557
3
Erasmus University Medical Center, Rotterdam, the Netherlands; Division of
Ferrata Storti Foundation
Coagulation and its Disorders
Desmopressin in moderate hemophilia A patients: a treatment worth considering
Janneke I. Loomans,1 Marieke J.H.A. Kruip,2 Manuel Carcao,3
Shannon Jackson,4 Alice S. van Velzen,1 Marjolein Peters,1
Elena Santagostino,5 Helen Platokouki,6 Erik Beckers,7 Jan Voorberg,8 Johanna G. van der Bom9,10 and Karin Fijnvandraat1,8 for the RISE consortium
1Department of Pediatric Hematology, Immunology and Infectious diseases,
Emma Children’s Hospital, Amsterdam, the Netherlands; 2Department of Hematology,
Haematology/Oncology, Department of Paediatrics and Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada; 4Division of Hematology, Department of Medicine, St. Paul’s Hospital and University
of British Columbia, Vancouver, BC, Canada; 5A. Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca’ Granda Foundation, Maggiore Hospital Policlinico, Milan, Italy; 6Aghia Sofia Children’s Hospital, Athens, Greece; 7Maastricht University Medical Centre, the Netherlands; 8Department of Plasma Proteins, Sanquin Research, Amsterdam, the Netherlands; 9Leiden University Hospital, the Netherlands
and 10Sanquin Research, Leiden, the Netherlands
ABSTRACT
Desmopressin increases endogenous factor VIII levels in hemophilia A. Large inter-individual variation in the response to desmopressin is observed. Patients with a lower baseline factor VIII activity tend to show a reduced response, therefore, desmopressin is less frequently used in moderate hemophilia A patients (baseline factor VIII activity 1-5 international units/deciliter), even though factor VIII levels may rise sub- stantially in some of them. We aim to describe the response to desmo- pressin in moderate hemophilia A patients and to identify predictors. We selected data on 169 patients with moderate hemophilia from the multi- center Response to DDAVP In non-severe hemophilia A patients: in Search for dEterminants (RISE) cohort study. Adequate response to desmopressin was defined as a peak factor VIII level ≥ 30, and excellent response as ≥ 50 international units/deciliter after desmopressin adminis- tration. We used univariate and multiple linear regression techniques to analyze predictors of the peak factor VIII level. Response was considered adequate in 68 patients (40%), of whom 25 showed excellent response (15%). Intravenous administration, age, pre-desmopressin factor VIII activity and von Willebrand factor antigen, peak von Willebrand factor activity and desmopressin-induced rise in von Willebrand factor antigen were significant predictors of peak factor VIII level and explained 65% of the inter-individual variation. In 40% of moderate hemophilia A patients, desmopressin response was adequate, thus it is important not to with- hold this group of patients from desmopressin responsiveness. Among the six predictors that we identified for desmopressin-induced factor VIII rise, factor VIII activity and desmopressin-induced rise in von Willebrand factor antigen had the strongest effect.
Introduction
Hemophilia A (HA) is a hereditary clotting disease caused by mutations in the F8 gene, leading to a deficiency of clotting factor VIII (FVIII) that occurs in one out of 5,000 men. Patients are classified based on residual levels of FVIII activity (FVIII:C). Severe patients have no detectable FVIII:C, non-severe patients have some activity (moderate FVIII:C 1-5 and mild 6-40 IU/dL).
Severe and moderate HA patients are generally treated with FVIII concentrates, whereas most mild HA patients may be successfully treated with 1-Deamino-8-D- ArgininVasoPressin (desmopressin; DDAVP) for minor injuries or procedures. Using DDAVP, and thereby avoiding FVIII concentrates, has two important advantages: depending on the country, DDAVP is much cheaper than FVIII concentrate, and DDAVP does not carry the risk of inhibitor development associated with the use of exogenous (allogeneic) sources of FVIII present in concentrates.1-3
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