PB0150 - Fibrin clot formation is a reliable biological marker to evaluate FVIII replacement therapy in hemophilia A patients.

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Debora Bertaggia Calderara, PhD

Research Associate
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland

Co-Author(s)

AB

Ana Patricia P. Batista Mesquita Sauvage

Specialized clinical nurse
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
FG

Francisco Javier J. Gomez

Head technician
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
MZ

Maxime Grégoire G. Zermatten

Physician assistant
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
Lucas Veuthey, BSc, MSc (he/him/his)

PhD student
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
Durre Shehwar, MSc MPhil

PhD Student
Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan
Islamabad, Islamabad, Pakistan
Cindy Pereira Portela, MD Student

MD student
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
Alessandro Aliotta, PhD

Research Associate
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
LA

Lorenzo Alberio, MD (he/him/his)

Chief Physician, Associated Professor
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland

Background: Hemophilia A (HA) is classified according to factor VIII (FVIII) baseline activity and is usually treated with FVIII concentrates, whose effectiveness is monitored by FVIII plasma levels. However, patients with similar FVIII activity display wide heterogeneous bleeding phenotypes. This observation endorses the concept that FVIII level does not completely reflect the hemostatic status of individual patients.

Aims: Our aim was to evaluate whether global coagulation assays (GCA), measuring thrombin generation (TG) and fibrin clot formation (FCF), better describe the clinical response of HA patients receiving replacement therapy.

Methods: TG and FCF were measured with Calibrated-Automated-Thrombogram assay (Stago, France) and with Thrombodynamics analyzer (Hemacore, Russia) respectively, in hemophilic plasma from adult HA patients (n=47), at baseline and during replacement therapy (with standard or extended half-life FVIII concentrates). TG parameters were peak height (PH, nM), velocity index (VI, nM/min), endogenous thrombin potential (ETP, nM thrombin*min). FCF parameters were initial and stationary-rate of clot growth (Vi and V, um/min), clot size (CS, um).

Results: i) Comparison of baseline values showed that FCF discriminated the degree of disease severity (severe versus moderate) while TG did not. ii) FCF overlapped across categories of disease severity, possibly capturing the individual baseline hemostatic state better than single factor activity; iii) Both TG and FCF correlated to FVIII activity during monitoring of replacement therapy. However, FCF showed better correlation especially when FVIII values were below 40% (Fig.1).

Conclusion(s): GCA seem to capture inter-individual differences in the baseline coagulation potential of patient with HA having similar levels of FVIII activity. FCF seems to be more sensitive in discriminating patient phenotype at baseline and during monitoring of replacement therapy compared to TG, especially at low levels of FVIII. In conclusion, FCF might be a reliable biological marker for assessing individual baseline bleeding risk and pharmacodynamics monitoring of replacement therapy in patients with HA.