Factor VIII Prophylaxis Effects Outweigh Other Hemostasis Contributors in Predicting Severe Hemophilia A Joint Outcomes

Details

• Alternative Title:
  Haemophilia
• Personal Author:
  Warren, Beth Boulden ; Jacobson, Linda ; Kempton, Christine ; Buchanan, George R. ; Recht, Michael ; Brown, Deborah ; Leissinger, Cindy ; Shapiro, Amy D. ; Abshire, Thomas C. ; Manco-Johnson, Marilyn J
• Corporate Authors:
  Joint Outcome Study Group Investigators Manco-JohnsonMarilyn J.MDAbshireThomas C.MD.ShapiroAmy D.MDRiskeBrendaMS, MBA, MPAHackerMichele R.Sc.D.KilcoyneRayMDIngramJ. DavidMDManco-JohnsonMichael L.MDFunkSharonB.Sc., PTJacobsonLindaBSValentinoLeonard A.MDHootsW. KeithMDBuchananGeorge R.MDDiMicheleDonnaMDRechtMichaelMD,PhDBrownDeborahMDLeissingerCindyMDBleakShirleyMSNCohenAlanMDMathewPrasadMDMatsunagaAlisonMDMedeirosDesireeMDNugentDianeMDThomasGregory A.MDThompsonAlexis A.MDMcRedmondKevinMDSoucieJ. MichaelPhDAustinHarlanPhDEvattBruce L.MD
• Description:
  Introduction:
  
  The Joint Outcome Study (JOS) demonstrated that previously untreated children with severe hemophilia A treated with prophylactic factor VIII (FVIII) concentrate had superior joint outcomes at age six 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 Factor VIII Female Global Assays Haemophilia Hemophilia A Hemostasis Humans Joint Diseases Joints Male Pediatric Prophylaxis

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• Source:
  Haemophilia. 25(5):867-875
• Pubmed ID:
  31115111
• Pubmed Central ID:
  PMC7273872
• Document Type:
  Journal Article
• Funding:
  U27/CCU812106/CC/CDC HHSUnited States/ ; M01 RR000069/RR/NCRR NIH HHSUnited States/ ; U27 CCU812106/ImCDC/Intramural CDC HHSUnited States/ ; U27 CCU812106/CC/CDC HHSUnited States/
• Volume:
  25
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:0787a234d680489221e35da3995107f71df292fe8ba0e9cd4039c31d77c7a9c1
• Download URL:
  https://stacks.cdc.gov/view/cdc/88956/cdc_88956_DS1.pdf
• File Type:
  [PDF - 467.63 KB ]