CC BY 4.0 · Thromb Haemost 2020; 120(05): 728-736
DOI: 10.1055/s-0040-1709519
Coagulation and Fibrinolysis
Georg Thieme Verlag KG Stuttgart · New York

Modeling to Predict Factor VIII Levels Associated with Zero Bleeds in Patients with Severe Hemophilia A Initiated on Tertiary Prophylaxis

Pratima Chowdary
1  Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free London NHS Foundation Trust, London, United Kingdom
,
Kathelijn Fischer
2  Van Creveldkliniek, Department of Hematology, University Medical Center, Utrecht, The Netherlands
,
Peter W. Collins
3  School of Medicine, Cardiff University, Cardiff, United Kingdom
,
Amy Cotterill
4  Baxalta Innovations GmbH, a member of the Takeda group of companies, Vienna, Austria
,
Barbara A. Konkle
5  Bloodworks Northwest, Seattle, Washington, United States
6  Department of Medicine, University of Washington, Seattle, Washington, United States
,
Victor Blanchette
7  Department of Paediatrics, Division of Haematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
,
Steven W. Pipe
8  Department of Pediatrics and Pathology, University of Michigan, Ann Arbor, Michigan, United States
,
Erik Berntorp
9  Department of Translational Medicine and Centre for Thrombosis and Haemostasis, Lund University, Malmö, Sweden
,
Martin Wolfsegger
4  Baxalta Innovations GmbH, a member of the Takeda group of companies, Vienna, Austria
,
Werner Engl
4  Baxalta Innovations GmbH, a member of the Takeda group of companies, Vienna, Austria
,
Gerald Spotts
10  Baxalta US Inc, a member of the Takeda group of companies, Lexington, Massachusetts, United States
› Author Affiliations
Funding This study was funded by Baxalta US Inc, a member of the Takeda group of companies, Lexington, Massachusetts, United States.
Further Information

Publication History

22 November 2019

20 February 2020

Publication Date:
05 May 2020 (online)

  

Abstract

Background Factor VIII (FVIII) trough levels > 1 IU/dL in patients with severe hemophilia A receiving regular prophylaxis may optimize bleed protection.

Objectives In this post hoc analysis of patients receiving tertiary prophylaxis for approximately 1 year, the relationship between estimated FVIII levels and reported bleeds was investigated to predict the potential for zero bleeds.

Methods Sixty-three patients (median [range] age, 28 [7–59] years) with severe hemophilia A (229 bleeds) were included. FVIII levels at time of each bleed were estimated from single-dose individual pharmacokinetics. The highest estimated FVIII level at which patients experienced a bleed was considered the “potentially effective trough level” for that bleed type. Kaplan–Meier estimates of proportions of patients with no bleeds above certain estimated FVIII levels were determined. Those not experiencing a bleed in the trial were assumed to have a bleed at 0 IU/dL (pragmatic approach) or at their median trough level (conservative approach).

Results Kaplan–Meier estimates based on pragmatic approach predicted zero all bleeds, joint bleeds, and spontaneous joint bleeds in 1 year in 40, 43, and 63% of patients, respectively, when the potentially effective trough FVIII level was set at 1 IU/dL. Between 1 and 10 IU/dL, every 1 IU/dL rise in estimated FVIII level was associated with an additional 2% of patients having zero all bleeds.

Conclusion This post hoc analysis confirms benefits with trough levels of approximately 1 to 3 IU/dL in most patients starting tertiary prophylaxis; prophylaxis with higher trough levels may help patients to achieve zero bleeds.

Authors' Contributions

P.C., K.F., P.W.C., and G.S. jointly designed the analysis, interpreted the results, and wrote the first draft of the manuscript. A.C. performed the statistical analysis and discussed and interpreted the results. B.A.K., V.B., and S.W.P. discussed and interpreted the results. E.B. participated in designing the study and discussed and interpreted the results. M.W. performed the PK analysis and discussed and interpreted the results. W.E. revised the graphical representation of results and discussed and interpreted the results. All authors reviewed the manuscript drafts and approved the final version.