Desmopressin in moderate hemophilia A patients: a treatment worth considering
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1 Published Ahead of Print on January 5, 2018, as doi: /haematol Copyright 2018 Ferrata Storti Foundation. Desmopressin in moderate hemophilia A patients: a treatment worth considering by Janneke I. Loomans, Marieke J.H.A. Kruip, Manuel Carcao, Shannon Jackson, Alice S. van Velzen, Marjolein Peters, Elena Santagostino, Helen Platokouki, Erik Beckers, Jan Voorberg, Johanna G. van der Bom, and Karin Fijnvandraat Haematologica 2017 [Epub ahead of print] Citation: Janneke I. Loomans, Marieke J.H.A. Kruip, Manuel Carcao, Shannon Jackson, Alice S. van Velzen, Marjolein Peters, Elena Santagostino, Helen Platokouki, Erik Beckers, Jan Voorberg, Johanna G. van der Bom, and Karin Fijnvandraat. Desmopressin in moderate hemophilia A patients: a treatment worth considering. Haematologica. 2017; 102:xxx doi: /haematol Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in print on a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process.
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28 SUPPLEMENTAL MATERIALS All patients No absolute response Partial absolute response Complete absolute response Treatment, n Reason for treatment, n Dental procedure Bleeding Unknown Bleeding location, bleeding severity and treatment outcome* Hand, major, poor Ankle, minor, moderate Tongue, major, moderate Unknown, unknown, moderate All unknown Supplemental Table 1. DDAVP treatment outcome and absolute response in moderate patients. This table displays the treatment-related DDAVP administrations in our cohort. *Treatment outcome was defined as follows: - Poor: severe, uncontrolled bleeding did not stop (or was not prevented in case of surgery) within 24 hours and required additional therapy (other than DDAVP). - Moderate: moderate bleeding in excess of what would be expected for a patient without a bleeding disorder; could not optimally be treated or prevented. - Adequate: adequate control/prevention of bleeding, blood loss did not exceed what would be expected in normal hemostasis. Bleeding stopped within a few hours and did not recur after one administration. The patient did not require additional product or unplanned treatment.
29 Results: Nine patients received DDAVP for treatment of which eight administrations were subcutaneous and one was intravenous. Three patients received DDAVP for a dental procedure, of whom the therapeutic response to DDAVP was unknown. The absolute response was partial in two patients and complete in one patient. Five patients were treated for a bleeding with DDAVP. One patient had a minor bleeding in his ankle. The therapeutic response to DDAVP was moderate and absolute response to DDAVP was partial in this patient. Two patients had a major bleeding, one in his tongue and the other in his left hand with respectively a moderate and poor therapeutic response. The patient with the moderate therapeutic response showed a complete absolute response whereas the patient with a poor therapeutic response had no absolute response. The two other patients had bleeding of unknown severity. One patient had a moderate therapeutic response, but both of them had no absolute response. Discussion: Two out of four patients receiving treatment in the study by Stoof et al. were moderate patients. DDAVP was given intravenously for a bleeding in the psoas major muscle and for a kidney bleed. Treatment outcome was respectively poor and unknown. 15 Specific bleeding results from de La Fuente et al. could not be retrieved. 19 Ghirardini et al. describe one moderate patient who received DDAVP for dental extraction, which occurred without bleeding. 18 One patient received DDAVP for muscle hematoma, resulting in a prompt cessation of bleeding. 18 Both administrations were subcutaneous and showed no absolute response (incremental 3 and 4 respectively). Warrier et al. described the intra-nasal administration of DDAVP to one moderate patient who received minor oral surgery without any unusual bleeding and no absolute response. 21
30 Variable Missing Total Percent Baseline VWF:Act 87 54,7% Baseline VWF:Ag 53 33,3% Peak VWF:Act ,2% Peak VWF:Ag ,1% Bloodgroup O 95 59,7% Age at DDAVP response 11 6,9% Supplemental Table 2. Missing data predictor variables multivariate analyses.
31 APPENDIX A RISE consortium. The investigators and institutions participating in the RISE study are as follows: Steering Committee: K. Fijnvandraat (principal investigator and chair), M. Peters, Academic Medical Center, Amsterdam; J. G. van der Bom, Leiden University Medical Center and Sanquin Research, Leiden; M.J.H.A. Kruip, Erasmus University Medical Center Rotterdam, The Netherlands; E. Santagostino, IRCCS Maggiore Hospital Foundation and University of Milan, Milan; G. Castaman, San Bortolo Hostpital, Vicenza & Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. Study Coordinator and Data Management: J.I. Loomans, Academic Medical Center, Amsterdam. Data collection: P. De Jong. Website and database: I. W. Corten. Study Sites, Principal Investigators and Local Collaborators: Australia: S. McRae, Royal Adelaide Hospital, Adelaide Austria: C. Male, Medical University of Vienna, Vienna Belgium: K. Peerlinck, University of Leuven, Leuven Canada: M. Carcao, SickKids Hospital, Toronto; S. Jackson, St. Pauls Hospital, Vancouver Finland: A. Mäkipernaa, Children s Hospital, Helsinki University Central Hospital, Helsinki Germany: C. Königs, JW Goethe University Hospital, Frankfurt Greece: H. Platokouki, Aghia Sophia Children's Hospital, Athens Italy: M.E. Mancuso, IRCCS Maggiore Hospital Foundation and University of Milan, Milan; M.G. Mazzuconni, C. Santoro, Hematology Sapienza University of Rome, Rome; A. Tagliaferri, G.F. Rivolta, University Hospital of Parma; G. Castaman, San Bortolo Hostpital, Vicenza & Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. Netherlands: K. Meijer, University Medical Centre Groningen, Groningen; M.R. Nijziel, Maxima Medical Center, Eindhoven; N. Dors, Catharina Hospital, Eindhoven; K. Hamulyak, E. Beckers, Maastricht University Medical Centre, Maastricht; P.P. Brons, B.A.P. Laros-van Gorkom, Radboud university medical center, Nijmegen; F.W.G. Leebeek, M.H. Cnossen, Erasmus University Medical Center, Rotterdam; E. Mauser-Bunschoten, K. Fischer, University
32 Medical Center Utrecht, Utrecht; K. Fijnvandraat, M. Peters, Academic Medical Center, Amsterdam. Spain: S. Haya, A. Moret, A.R. Cid, P. Casaña, Hospital Universitario la Fe, Valencia Sweden: P. Petrini, M. Holmström, Karolinska University Hospital, Stockholm United Kingdom: T.T. Yee, Royal Free Hospital; S. Rangarajan, G. Thompson, Guy s & St. Thomas NHS Foundation Trust both in London, the United Kingdom;
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