Factor VIII Activity Levels Matter
Lower Factor VIII levels put patients at greater risk for bleeds1,2
WFH Guidelines,* along with a retrospective analysis,† have shown that at Factor VIII levels of 5% to <40% (mild hemophilia), patients are vulnerable to traumatic, joint, and surgical bleeds, including subclinical bleeds.1,2
Higher Factor VIII levels are associated with the ability to perform activities with lower risk of a bleed1,3‑6*‡§ll
Higher Factor VIII levels reduce bleeding risk and may enable patients to live a more active life1,3‑6*‡§ll
* Data from the 2020 WFH Guidelines for the Management of Hemophilia, 3rd edition.1,7
† Data from a study including 63 patients with severe hemophilia A treated with prophylaxis for at least 180 days.2
‡ Data from a 2021 systematic review of physical activity in people with hemophilia across multiple databases, extracted using a standardized template and reported using a narrative synthesis.4
§ Data from an expert elicitation study using Sheffield Elicitation Framework methodology quantified with probability analysis.5
ll Data from a Delphi consensus statement using structured expert opinion to define target factor levels for use in different clinical situations.6
¶ WFH Guidelines define the upper limit of mild hemophilia as 40% factor activity, and the WFH Introduction to Hemophilia defines the normal range as 50% to 150%, which indicates that 40% to 50% would be in between mild hemophilia and normal, here referred to as “near-normal” levels.1,7
Is it time for a higher level of protection?
Achieving higher Factor VIII levels has the potential to:
Provide greater protection from bleeds8,9*†
Preserve joint health1,10,11‡§ǁ
Reduce pain1,11,12§ǁ¶
Improve physical function1,4,5,11§ǁ#**
The level of bleed protection depends on the levels of Factor VIII1,2ll††
* Data from a post-hoc analysis of the association of Factor VIII levels and AUC with annualized bleeding rate in 34 patients on pharmacokinetic-guided prophylaxis.8
† Data from a 2021 review of prophylaxis in hemophilia with respect to pharmacokinetics, alongside other factors that contribute to clinical decision-making.9
‡ Data from a retrospective analysis of effect of hemophilia type and factor level on joint bleeding and orthopedic procedures in 4771 males with nonsevere hemophilia A or B without inhibitors receiving on-demand factor replacement therapy over a 12-year period.10
§ Data from a randomized, controlled trial of secondary/tertiary prophylaxis vs on-demand treatment in adult and adolescent patients with severe hemophilia A over 3 years.11
ll Data from the 2020 WFH Guidelines for the Management of Hemophilia, 3rd edition.1,7
¶ Data from a post-hoc analysis of patient-reported pain surveys and joint health examinations assessing the association of demographic and clinical characteristics with perceptions of pain and functional abilities in 240 adult patients with hemophilia A or B (with or without inhibitors) and a history of joint pain or bleeding.12
# Data from a 2021 systematic review of physical activity in people with hemophilia across multiple databases, extracted using a standardized template and reported using a narrative synthesis.4
** Data from an expert elicitation study using Sheffield Elicitation Framework methodology quantified with probability analysis.5
†† Data from a study including 63 patients with severe hemophilia A treated with prophylaxis for at least 180 days.2
Improving bleed protection may allow closer-to-normal activity for patients with hemophilia A
Factor VIII levels and their impact on the ability to perform activities
| Factor VIII Activity Levels1,3,6,7,13 | Impact on Physical Activity1,3,6,13 |
| Normal levels 50%-150% factor activity | None to minimal1,5,6 High-impact activity possible with no pain (sports, physically taxing jobs). |
| Near normal* ≥40%-<50% factor activity | Near-normal factor levels are currently undefined by the World Federation of Hemophilia. |
| Mild hemophilia 5%-<40% factor activity | Minor6,13 High-risk activity is possible. Intensive sport activity may be considered for those with factor levels between 15%-30%. Appropriate level of physical activity should be evaluated on a case-by-case basis. May experience pain and limited mobility. |
| Moderate hemophilia 1%-5% factor activity | Moderate6,13 Factor levels between 1%-3% may be sufficient for those with a sedentary lifestyle, but higher levels between 3%-5% are recommended if engaging in mild physical activity. Individuals should refrain from high-risk activity. May experience pain and limited mobility. |
| Severe hemophilia <1% factor activity | Major1,5,6 High risk of spontaneous bleeds—even with low activity there will be pain in target joints. |
As Factor VIII levels approach normal, patients are less likely to experience bleeds1†
* WFH Guidelines define the upper limit of mild hemophilia as 40% factor activity, and the WFH Introduction to Hemophilia defines the normal range as 50% to 150%, which indicates that 40% to 50% would be in between mild hemophilia and normal, here referred to as “near-normal” levels.1,14
† Factor levels should be assessed based on an individual patient basis.
Indication
AUC=area under the curve; FVIII=Factor VIII; MOE=mechanism of extension; PK=pharmacokinetics; WFH=World Federation of Hemophilia.
References: 1. Srivastava A, et al. Haemophilia. 2020;26(suppl 6):1-158. 2. Chowdary P, et al. Thromb Haemost. 2020;120(5):728-736. 3. Centers for Disease Control and Prevention. Diagnosis of Hemophilia. Updated August 1, 2022. Accessed January 8, 2023. https://www.cdc.gov/ncbddd/hemophilia/diagnosis.html 4. Kennedy M, et al. Haemophilia. 2021;27(4):544-562. 5. Martin AP, et al. Haemophilia. 2020;26(4):711-717. 6. Iorio A, et al. Haemophilia. 2017;23(3):e170-e179. 7. National Hemophilia Foundation. Hemophilia A. Accessed January 8, 2023. https://www.hemophilia.org/bleeding-disorders-a-z/types/hemophilia-a 8. Valentino LA, et al. Haemophilia. 2016;22(4):514-520. 9. Berntorp E, et al. Blood Rev. 2021;50:100852. 10. Soucie JM, et al. Blood Adv. 2018;2(16):2136-2144. 11. Manco-Johnson MJ, et al. J Thromb Haemost. 2017;15(11):2115-2124. 12. Kempton CL, et al. Eur J Haematol. 2018;100(suppl 1):25-33. 13. Skinner MW, Nugent et al. Haemophilia. 2020;26(1):17-24. 14. Hemophilia. eLearning Platform. (2023, December 15). WFH website. eLearning platform: Hemophilia. https://elearning.wfh.org/elearning-centres/hemophilia/ Accessed April 17, 2024.
