PB1143 - The Thrombin Generation Test represents a better tool than Factor VIII levels to assess the risk of bleedings in patients with hemophilia A

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

AB

Angel Bernardo

Hematology
HUCA
oviedo, Asturias, Spain
IS

Inmaculada Soto

Head of Department
Department of Hematology, Central University Hospital of Asturias
Oviedo, Asturias, Spain
LG

Laura Gutiérrez

Principal Investigator - Platelet Research Lab
University of Oviedo - ISPA
Oviedo, Asturias, Spain
AC

Alberto Caro

Medical Doctor
Department of Hematology, Central University Hospital of Asturias
Oviedo, Asturias, Spain
DM

Daniel Martínez-Carballeira

Medical Doctor
Department of Hematology, Central University Hospital of Asturias
Oviedo, Asturias, Spain
JC

Jose Ramon Corte Buelga

PhD
HOSPITAL UNIVERSITARIO CENTRAL DE ASTURIAS
Oviedo, Asturias, Spain
SV

Sonia Vázquez

Medical Doctor
Department of Hematology, Central University Hospital of Asturias
Oviedo, Asturias, Spain
CP

Carmen Palomo-Antequera

Medical Doctor
Department of Internal Medicine, Central University Hospital of Asturias
Oviedo, Asturias, Spain
AA

Alfredo Andreu

Researcher
Department of Pharmacology, University of Navarra
Pamplona, Navarra, Spain
AF

Alvaro Fernández-Pardo

Researcher
Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe
Valencia, Comunidad Valenciana, Spain
Julia Oto

Postdoctoral Researcher
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain

Presenting Author(s)

PM

Pilar Medina

PI
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain

Background: Hemophilia A (HA) is a rare bleeding disorder caused by factor VIII (FVIII) deficiency due to mutations in the F8 gene. Disease severity inversely correlates with plasma FVIII (FVIII:C) concentration. Unaccountably, a subgroup of severe HA patients scarcely bleed and do not require prophylactic FVIII administration, while moderate HA patients bleed frequently, despite their FVIII:C levels.

Aims: To evaluate the capacity of the ST Genesia® Thrombin Generation System (TGT) to ascertain the hemostatic status of the entire cohort of HA outpatients, treated and non- bleeding, in Asturias (Spain) and to compare it with FVIII performance.

Methods: We recruited 55 HA patients (18 severe, 7 moderate and 30 mild; FVIII:C < 40%) following treatment and without inhibitors, and 25 healthy controls. HA patients were monitored assessing FVIII activity (and vWF levels) at diagnosis and follow-up, and screened for F8 mutations. The TGT BleedScreen was evaluated during follow-up.

Results: Patients with severe/moderate HA had lower FVIII:C at diagnosis and a higher annual bleeding rate (ABR) than mild HA patients (P < 0.001) (Table 1). Importantly, on the day of the TGT and despite having lower FVIII:C, severe/moderate patients had a similar thrombin potential than mild patients, reflecting better the non-bleeding phase of our patient cohort (Figure 1). Additionally, a correlation of the F8 mutation type was observed with HA severity, ABR and hemostatic status.

Conclusion(s): The hemostatic status of HA patients measured with ST Genesia® correlates more precisely with their bleeding risk than classical FVIII:C. The F8 mutation type may indicate a worse prognosis, higher ABR and worse hemostatic status. The TGT may represent a more suitable tool than classical FVIII:C determination to identify HA patients that may require a closer follow-up and a tailored therapeutic adjustment in high-risk situations. MINECO (RYC-2013-12587), MICIU (SAF2017-85489-P), Roche (SP200221001), GVA (ACIF/2017/138) and Sociedad Española de Trombosis y Hemostasia.