OC 24.3 - Minimum Baseline FVIII Levels Required to Prevent Joint Bleeding Episodes: a Study in Mild Hemophilia A

Sunday, June 25, 2023

15:15 – 15:30 ET

Room: 520

Session Available As: On-Demand

Presenting Author(s)

Pasquale Agosti, MD, PhD

Università degli Studi di Milano, Department of Pathophysiology and Transplantation and Fondazione Luigi Villa, Milan, Italy
Milano, Lombardia, Italy

Co-Author(s)

SS

Simona Maria Siboni

Hematologist
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center
Milan, Lombardia, Italy
SS

Sara Scardo

Statistician
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
Milan, Lombardia, Italy
Roberta Gualtierotti, MD, PhD

Associate Professor
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centro Emofilia e Trombosi Angelo Bianchi Bonomi
Milan, Lombardia, Italy
Flora Peyvandi, MD, PhD (she/her/hers)

Director
IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy; Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milano, Italy
Milano, Lombardia, Italy

Background: The severity of the bleeding phenotype in hemophilia A (HA) patients correlates with the degree of coagulation factor VIII (FVIII) deficiency in plasma. However, it is not clear which is the needed target FVIII level to achieve the goal of zero joint bleeds.

Aims: To identify the minimum FVIII level necessary to prevent joint bleeds in HA patients.

Methods: In this retrospective cohort study, mild congenital HA patients aged 16 years or more, regularly followed at the Angelo Bianchi Bonomi Hemophilia and Thrombosis center were enrolled. Patients with other coagulopathies, history of FVIII inhibitors, or on FVIII prophylaxis were excluded. Age, blood group, FVIII levels and joint bleeds occurred in life were collected.

Results: We included 271 male patients, with a mean age of 46 years and mean FVIII level in life of 24 IU/dL. One hundred (37%) had a history of joint bleeds in life, 10 (4%) with at least a spontaneous joint bleed. The mean annualized joint bleeding rate (AJBR) and spontaneous AJBR were 0.0155 [standard deviation (SD): 0.0317] and 0.0014 (SD: 0.0097), respectively. Lower mean FVIII levels were observed in patients having a history of joint bleeds (17.8 vs 26.8, p< 0.0001). After adjusting for age and blood group, with every IU/dL increase of FVIII level, we observed a 7% reduction of AJBR and a 34% reduction of spontaneous AJBR (Table 1).
The minimum FVIII trough level needed to prevent any and spontaneous joint bleeds lifelong resulted to be 19.2 IU/dL and 17.7 IU/dL, respectively (Table 2).

Conclusion(s): In our large Italian cohort of mild HA patients, we identified the minimum target FVIII level to prevent total and spontaneous joint bleeds (19.2 and 17.7 IU/dL, respectively). These findings could contribute to identify the target level to be attained in the frame of optimal prophylaxis and gene therapy.

Learning Objectives:

Upon completion, participant will be able to describe and explain the bleeding phenotype in patients with mild hemophilia A.
Upon completion, participant will be able to predict the bleeding phenotype in patients with mild hemophilia A according to baseline FVIII levels.
Upon completion, participant will be able to define the trough FVIII level necessary to prevent total and spontaneous joint bleeds in patients with mild hemophilia A.