PB1411 - Altered whole blood thrombin generation and hyperresponsive platelets associate with thromboembolic events in patients with pancreatic ductal adenocarcinoma

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

RW

Ruth Willems

MD, Phd Student
Synapse Research Institute
Maastricht, Limburg, Netherlands

Co-Author(s)

Ilaria De Simone, PhD

PostDoc
Synapse Research Institute
Maastricht, Limburg, Netherlands
Joke Konings, PhD

Senior Scientist
Synapse Research Institute
Maastricht, Limburg, Netherlands
Dana Huskens, PhD

PhD, Senior Research Project Leader
Synapse Research Institute
Maastricht, Limburg, Netherlands
Hugo ten Cate, MD, PHD

MD, PhD
Departments of Internal Medicine and Biochemistry, Maastricht University Medical Center+, Maastricht, The Netherlands
Maastricht, Limburg, Netherlands
Jd

Judith de Vos-Geelen

MD, PhD
Maastricht University Medical Center
Maastricht, Limburg, Netherlands
Bd

Bas de Laat

General Director
Synapse Research Institute
Maastricht, Limburg, Netherlands
Mark Roest

PhD, Clinical Director
Synapse Research Institute
Maastricht, Limburg, Netherlands

Background: Thromboembolic disease is a major complication in pancreatic ductal adenocarcinoma (PDAC) patients. PDAC patients often have altered blood cell counts, which associate with incident thrombosis. The high thrombotic risk may be partially explained by pro-coagulant blood cells. This risk could be further influenced by fibrinolysis, which counterbalances thrombus formation.

Aims: 1. To compare blood cell dependent coagulation and fibrinolysis between PDAC patients and controls
2. To explore whether blood cell-dependent coagulation and fibrinolysis associate with incident thrombosis in PDAC patients

Methods: Locally advanced and metastatic PDAC patients and controls matched for age and sex were included. Thrombin generation (TG) was measured in whole blood (WB) and plasma. Platelet granule release capacity (PGRC) was measured in WB. Plasmin generation (PG) was measured in plasma. Patients were followed for thromboembolic event occurrence during 6-months.

Results: In contrast to plasma, patients (n=18) showed increased endogenous thrombin potential (ETP) in WB, compared to controls (n=18; 2714 vs. 2905, p=0.003). Lag time was longer in patients, in both WB (10.5 vs. 8.9 minutes, p=0.013) and plasma (7.6 vs. 6.2, p=0.006). Patients had higher endogenous plasmin potential and longer lag time to PG than controls (418 vs. 319, p< 0.001; 3.2 vs 2.8, p=0.002). Patients had hyperresponsive platelets, with shorter time to PGRC (43 vs. 62 seconds, p=0.008). Five patients developed thromboembolic events. A shorter WB lag time (HR=0.475, 95%-CI=(0.228-0.988)), not in plasma, and increased PGRC (HR=1.148, 95%-CI=(1.007- 1.309)) associated with thrombosis.

Conclusion(s): Patients with PDAC have an increased and delayed WB-TG coagulation profile compared to controls. The increase in coagulation was not found in plasma, implying blood-cell dependent procoagulant effects. Additionally, patients have an increased and delayed fibrinolysis profile. Blood cell-dependent coagulation associates with incident thromboembolic events and platelets appear to play a key role. Hemostasis measurement in WB is likely to improve thrombosis risk estimation in PDAC patients.