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Author Notes:

Paula D. James, Department of Medicine, Queen's University, Room 2015 Etherington Hall, 94 Stuart St, Kingston ON K7L 3N6, Canada; e-mail:jamesp@queensu.ca

Contribution: V.C. contributed to the design of the study, performed experiments, collected data, analyzed and interpreted the data, and drafted the manuscript; P.D.J. designed the study, supervised the research, analyzed and interpreted the data, and drafted the manuscript; R.F.S. designed the study, recruited subjects, and collected data; H.W. recruited subjects and collected data; W.M.H. assisted with statistical analysis; D.G. coordinated sample assessment; L.T. performed phlebotomy and performed the desmopressin trials; J.G. recruited subjects and collected data; M.B. contributed to experiments; L.H. performed thromboelastography; and all authors revised the manuscript.

Conflict-of-interest disclosure: P.D.J. has received research funding from CSL Behring, Bayer, and Shire. R.F.S. has received research funding from Bioverativ, Kedrion/Grifols, Genentech, and Shire and has received honoraria from Shire, Genentech/Roche, CSL Behring, Bioverativ, Uniqure, Biomarin, Bayer, and Novo Nordisk. The remaining authors declare no competing financial interests.


Research Funding:

This study was supported in part by research funding from the Hemostasis and Thrombosis Research Society Mentored Research Award.


  • Hemophilia A
  • Blood advances

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


Journal Title:

Blood Advances


Volume 2, Number 20


, Pages 2629-2636

Type of Work:

Article | Final Publisher PDF


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.

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© 2018 by The American Society of Hematology

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