Modeling to Predict Factor VIII Levels Associated with Zero Bleeds in Patients with Severe Hemophilia A Initiated on Tertiary Prophylaxis
(2020) In Thrombosis and Haemostasis 120(5). p.728-736- 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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2020-05-05
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- coagulation factors, factor VIII, hemophilia A/B, pharmacodynamics
- in
- Thrombosis and Haemostasis
- volume
- 120
- issue
- 5
- pages
- 9 pages
- publisher
- Schattauer GmbH
- external identifiers
-
- scopus:85084276989
- pmid:32369844
- ISSN
- 0340-6245
- DOI
- 10.1055/s-0040-1709519
- language
- English
- LU publication?
- yes
- id
- a090d5f1-3332-441e-91e7-526601dc5290
- date added to LUP
- 2020-06-09 14:47:57
- date last changed
- 2024-05-15 11:54:55
@article{a090d5f1-3332-441e-91e7-526601dc5290,
abstract = {{<p>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.</p>}},
author = {{Chowdary, Pratima and Fischer, Kathelijn and Collins, Peter W. and Cotterill, Amy and Konkle, Barbara A. and Blanchette, Victor and Pipe, Steven W. and Berntorp, Erik and Wolfsegger, Martin and Engl, Werner and Spotts, Gerald}},
issn = {{0340-6245}},
keywords = {{coagulation factors; factor VIII; hemophilia A/B; pharmacodynamics}},
language = {{eng}},
month = {{05}},
number = {{5}},
pages = {{728--736}},
publisher = {{Schattauer GmbH}},
series = {{Thrombosis and Haemostasis}},
title = {{Modeling to Predict Factor VIII Levels Associated with Zero Bleeds in Patients with Severe Hemophilia A Initiated on Tertiary Prophylaxis}},
url = {{http://dx.doi.org/10.1055/s-0040-1709519}},
doi = {{10.1055/s-0040-1709519}},
volume = {{120}},
year = {{2020}},
}