PB0172 - Thrombodynamics: a Novel Assay for Diagnostic Evaluation of Haemophilia A Patients

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Ryanne Astrid Arisz, MSc.

PhD student
Department of Hematology, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.
Rotterdam, Zuid-Holland, Netherlands

Co-Author(s)

LR

Lorenzo G.R. Romano, MD

PhD candidate
Department of Hematology, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
Rotterdam, Zuid-Holland, Netherlands
Jd

Janneke de Vries

Intern
Department of Hematology, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
Rotterdam, Zuid-Holland, Netherlands
Frank W.G. Leebeek, MD, PhD

Professor and Head of Department of Hematology
Erasmus MC, University Medical Center Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
SS

Saskia E.M. Schols

Internist-hematologist
Department of Hematology, Radboud university medical center, Nijmegen, The Netherlands. Hemophilia Treatment Center Nijmegen – Eindhoven – Maastricht, The Netherlands
Nijmegen, Gelderland, Netherlands
Jeroen C.J Eikenboom, MD. PhD

Professor, Head of Division of Thrombosis and Hemostasis
Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
Moniek P.M. de Maat, PhD

Professor
Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands

Background: The bleeding tendency in patients with haemophilia A is associated with FVIII activity levels and these are therefore used for classification of disease severity. However, also other determinants may influence bleeding tendency. A potentially valuable new assay to assess the hemostatic potential is thrombodynamics analysis, in which spatiotemporal clot growth and thrombin generation are measured in plasma.

Aims: To correlate thrombodynamics analysis with disease classification in haemophilia A patients.

Methods: We included nineteen patients with a mild (FVIII 0.12 IU/mL; n=5), moderate (0.04 IU/mL; n=7) or severe classification ( < 0.01 IU/ml; n=7) with blood sampling at least 48h after last prophylaxis treatment. Thrombodynamics (LLC Hemacore, Moscow, Russia) was performed in platelet poor plasma according to the instructions of the manufacturer. One plasma sample of a mild haemophilia A patient could not be measured due to a high lipid concentration and was excluded for analysis. Kruskal-Wallis analysis was performed for statistical analysis.

Results: Clot size and clotting speed were larger and higher in mild and moderate patients when compared to severe patients (Figure 1). Clot density, endogenous thrombin potential (ETP), and maximum thrombin concentration did not correlate with disease classification (Figure 1). A large variation in parameters was observed between patients with similar severity. For most, but not all patients, the clot density correlated with the ETP (Figure 2).

Conclusion(s): We identified clot density and ETP as parameters that present novel information on clot formation in haemophilia influenced by a other determinants apart from FVIII activity. The correlation between ETP and clot density, a parameter related to fibrin network properties, indicate that the density of the network is mainly determined by the concentration of activated thrombin concentration. Further analysis regarding clinical outcome of bleeding is necessary to establish whether these parameters are associated with bleeding tendency and to evaluate their additional diagnostic value.