PB1024 - Investigation of thrombin generation assay to assess vaso-occlusive crisis in sickle cell disease

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

GF

Guillaume Feugray

Dr
Normandie Univ, UNIROUEN, INSERM U1096, CHU Rouen, Vascular Hemostasis Unit, F-76000 Rouen, France
Rouen, Haute-Normandie, France
FK

Fiston Kasonga

Dr
CHU Rouen, Vascular Hemostasis Unit, F-76000 Rouen, France
Rouen, Haute-Normandie, France
MG

Maximilien Grall

Dr
CHU Rouen, Department of Internal Medecine, F-76000 Rouen, France
Rouen, Haute-Normandie, France
yb

ygal benhamou

MD,PhD
university hospital of rouen
rouen, Haute-Normandie, France

Presenting Author(s)

VL

Véronique Le Cam Duchez, MD PhD

Head of Hematology Laboratory
Rouen University Hospital
ROUEN, Haute-Normandie, France

Co-Author(s)

AL

Agnes Lahary

Dr
CHU Rouen, Hematology laboratory, F-76000 Rouen, France
Rouen, Haute-Normandie, France
pb

paul billoir

Pharm D, PhD
university hospital of rouen
Rouen, Haute-Normandie, France

Background: Sickle cell disease (SCD) is an inherited haemoglobinopathy disorder. The main consequence is synthesis of haemoglobin S leading to chronic haemolysis associated with morbidity.

Aims: The aim of this study was to investigate Thrombin Generation Assay (TGA) to assess hypercoagulability in SCD and TGA parameters as biomarkers of vaso-occlusive crisis (VOC).

Methods: We performed TGA in platelet poor plasma with 1pM of tissue factor and 4µM of phospholipid-standardized concentration. We measured soluble thrombomodulin, soluble endothelial Protein C Receptor and Tissue Factor Pathway Inhibitor. Experiments were done in duplicate for patients and controls.

Results: A total of 113 patients with SCD, 83 at steady state and 30 during VOC, and 25 controls were included. Among the 83 patients at steady state, 37 were S/S-1 S/β0, 20 were S/Sα3.7 and 19 were S/C-7 S/β+. Among the 83 patients at steady state, 28 developed a VOC in the following year (median: 4 months [2.25-6]).
We observed an increase of peak and velocity associated with a reduction of lagtime and time to peak and no difference of endogenous thrombin potential (ETP) in patients compared to controls. Decreases of physiological anticoagulants were also observed. TGA confirmed prothrombotic state in all SCD genotypes or clinical status. The association of an ETP>1207 nM.min and a peak>228.5 nM presented a sensitivity of 73.5% and a specificity of 93.9% to predict VOC development in the following year.

Conclusion(s): We have demonstrated a hypercoagulable state in SCD induced by chronic haemolysis. ETP and peak could be used to predict VOC development and to initiate new therapeutics in SCD.