A decreased and less sustained desmopressin response in hemophilia A carriers contributes to bleeding.

• Type of Material: Article
• Authors: Victoria Candy, Queen's University; Hilary Whitworth, Children's Healthcare of Atlanta; Julie Grabell, Children's Healthcare of Atlanta; Lisa Thibeault, Children's Healthcare of Atlanta; Lori Harpell, Queen's University; Mackenzie Bowman, Children's Healthcare of Atlanta; David Good, Queen's University; Wilma M. Hopman, Kingston General Hospital; Robert F. Sidonio Jr, Emory University; Paula D. James, Queen's University
• Language: English
• Date: 2018-10-23
• Publisher: American Society of Hematology: Blood Advances
• Publication Version: Final Published Version
• Copyright Statement: © 2018 by The American Society of Hematology
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2018023713
• Title of Journal or Parent Work: Blood Advances
• ISSN: 2473-9529
• Volume: 2
• Issue: 20
• Start Page: 2629
• End Page: 2636
• Grant/Funding Information: This study was supported in part by research funding from the Hemostasis and Thrombosis Research Society Mentored Research Award.
• Keywords: Blood advances; Hemophilia A
• Research Categories: Health Sciences, Pathology

Abstract

The cause of hemophilia A carrier bleeding is not well established. Desmopressin (DDAVP), used clinically to treat or prevent bleeding, can also be used as a medical stress surrogate. This study's objective was to compare the response to DDAVP in hemophilia A carriers with that in normal control patients. Bleeding was assessed by the International Society on Thrombosis and Hemostasis Bleeding Assessment Tool (ISTH-BAT). DDAVP (0.3 μg/kg) was administered either IV or subcutaneously (SC), and blood was drawn at baseline and 1, 2, and 4 hours postadministration. Blood was assessed for factor VIII (FVIII) level, von Willebrand factor (VWF) antigen (VWF:Ag), VWF activity (VWF:RCo or VWF:GPIbM), thromboelastography (TEG), and thrombin generation assay (TGA) at all points, and for VWF propeptide (VWFpp):Ag ratio and ABO blood type at baseline. Carriers were older than control patients (median age, 34 and 21 years, respectively; P = .003) and had higher ISTH-BAT bleeding scores (median bleeding score, 8 and 0, respectively; P = .001). Carriers had a significantly reduced FVIII response to DDAVP compared with control patients (P ≤ .0001). When only carriers with normal baseline FVIII levels (n = 10) were included, carriers maintained a reduced FVIII response (P ≤ .0001). Furthermore, participants with abnormal bleeding scores had a significantly lower FVIII response to DDAVP compared with those with normal bleeding scores (P = .036). Hemophilia A carriers have a lower and less sustained FVIII response to DDAVP, suggesting an impaired ability to respond to hemostatic stress, which contributes to bleeding.