Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Sep;25(5):867-875.
doi: 10.1111/hae.13778. Epub 2019 May 21.

Factor VIII prophylaxis effects outweigh other hemostasis contributors in predicting severe haemophilia A joint outcomes

Beth Boulden Warren  1 , Linda Jacobson  1 , Christine Kempton  2 , George R Buchanan  3 , Michael Recht  4   5 , Deborah Brown  6 , Cindy Leissinger  7 , Amy D Shapiro  8 , Thomas C Abshire  2   9 , Marilyn J Manco-Johnson  1 ; Joint Outcome Study Group Investigators
Collaborators, Affiliations

Factor VIII prophylaxis effects outweigh other hemostasis contributors in predicting severe haemophilia A joint outcomes

Beth Boulden Warren et al. Haemophilia. 2019 Sep.

Abstract

Introduction: The Joint Outcome Study (JOS) demonstrated that previously untreated children with severe haemophilia A treated with prophylactic factor VIII (FVIII) concentrate had superior joint outcomes at age 6 years compared to those children treated episodically for bleeding. However, variation in joint outcome within each treatment arm was not well explained.

Aim: In this study, we sought to better understand variation in joint outcomes at age 6 years in participants of the JOS.

Methods: We evaluated the influence of FVIII half-life, treatment adherence, constitutional coagulant and anticoagulant proteins, and global assays on joint outcomes (number of joint bleeds, total number of bleeds, total MRI score and joint physical exam score). Logistic regression was used to evaluate the association of variables with joint failure status on MRI, defined as presence of subchondral cyst, surface erosion or joint-space narrowing. Each parameter was also correlated with each joint outcome using Spearman correlations.

Results: Prophylaxis treatment arm and FVIII trough were each found to reduce risk of joint failure on univariate logistic regression analysis. When controlling for treatment arm, FVIII trough was no longer significant, likely because of the high level of covariation between these variables. We found no consistent correlation between any laboratory assay performed and any joint outcome parameter measured.

Conclusion: In the JOS, the effect of prescribed prophylactic FVIII infusions on joint outcome overshadowed the contribution of treatment adherence, FVIII half-life, global assays of coagulation and constitutional coagulation proteins. (ClinicalTrials.gov number, NCT00207597).

Keywords: blood coagulation factors; global assays; haemophilia; joints; paediatric; prophylaxis.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest

The remaining authors have no conflicts of interest to declare.

Figures

Figure 1:
Figure 1:
Scatter plots and regression lines of joint outcomes vs FVIII, thrombin generation ETP, antithrombin (AT) levels and TFPI levels.
See this image and copyright information in PMC

References

    1. Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007; 357: 535–44. - PubMed
    1. National Hemophilia Foundation Medical and Scientific Advisory Council (MASAC). MASAC Recommendation Concerning Prophylaxis. NHF MASAC Guidelines, 2016.
    1. Richards M, Williams M, Chalmers E, Liesner R, Collins P, Vidler V, et al. A United Kingdom Haemophilia Centre Doctors’ Organization guideline approved by the British Committee for Standards in Haematology: guideline on the use of prophylactic factor VIII concentrate in children and adults with severe haemophilia A. Br J Haematol 2010; 149: 498–507. - PubMed
    1. Berntorp E, Astermark J, Bjorkman S, Blanchette VS, Fischer K, Giangrande PL, et al. Consensus perspectives on prophylactic therapy for haemophilia: summary statement. Haemophilia 2003; 9 Suppl 1: 1–4. - PubMed
    1. Ar MC, Baykara O, Buyru AN, Baslar Z. The Impact of Prothrombotic Mutations on Factor Consumption in Adult Patients with Severe Hemophilia. Clin Appl Thromb-Hemost 2009; 15: 660–5. - PubMed

Associated data