Mathematical model of thrombin generation and bleeding phenotype in Amish carriers of Factor IX:C deficiency vs. controls

Details

• Journal Article:
  Thromb Res
• Personal Author:
  Gupta, S. ; Bravo, M.C. ; Heiman, M. ; Nakar, C. ; Brummel-Ziedins, K. ; Miller, C.H. ; Shapiro, A.
• Description:
  Introduction
  
  Factor IX:C (FIX:C) levels vary in hemophilia B carriers even in pedigrees with a unifying genetic defect. Analyzing the balance between pro-and anticoagulants might increase our understanding of carriers’ bleeding potential.
  
  Aim
  
  In this research study, we evaluated bleeding scores (BS) and a novel mathematical model of thrombin generation (TG) in Amish FIX:C deficient carriers and controls.
  
  Methods
  
  Blood samples and BS were obtained from post-menarchal females, including 59 carriers and 57 controls from the same extended pedigree. Factors II, V, VII, VIII, IX, X, antithrombin, tissue factor pathway inhibitor and protein C were assayed to generate mathematical models of TG in response to 5pM tissue factor (TF) and for TF + thrombomodulin. BS was based on a modification of the MCMDM-1VWD scoring system.
  
  Results
  
  Carriers had a lower mean FIX:C (68% vs. 119%), von Willebrand factor antigen (108 vs.133) and Tissue activatable fibrinolysis inhibitor (103 vs. 111) compared to controls; both groups had a similar mean BS. Carriers demonstrated significantly lower TG parameters on both mathematical models compared to controls. Carriers with FIX:C ≤ 50% had lower TG curves than those > 50% but similar BS.
  
  Conclusion
  
  Thrombin generation showed significant differences between carriers and controls, between low (≤50%) and high (> 50%) FIX:C carriers, and specifically in the TF + thrombomodulin model, between high FIX:C carriers and controls, although the BS were not different.
  
  
• Subjects:
  Article Bleeding Scores Carriers Hemophilia B Mathematical Model Thrombin Generation
• Source:
  Thromb Res. 182:43-50
• DOI:
  http://dx.doi.org/10.1016/j.thromres.2019.07.020
• Pubmed ID:
  31446339
• Pubmed Central ID:
  PMC7071813
• Document Type:
  Text ; Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHS/United States
• Genre:
  Journal Article
• Volume:
  182
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:84f37d87acb003f9d925ddee55d05bdc203e61755bfe05d1e87c1655a7f2281eb8237e2fe6a5d77aab3c70e9234f3f1c8a2c36cd760df58bfb4f5a92840def5e
• Download URL:
  https://stacks.cdc.gov/view/cdc/85866/cdc_85866_DS1.pdf
• File Type:
  [PDF - 897.82 KB ]