Altered whole blood thrombin generation and hyperresponsive platelets in patients with pancreatic cancer

INTRODUCTION: Thromboembolic disease is a major complication in patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often have altered blood cell counts, which associate with venous thromboembolism (VTE) development. The high thrombotic risk in patients with PDAC may be partially caused by pro-coagulant blood cells. METHODS: The aim of this study was to compare blood-cell dependent coagulation between patients with PDAC (n=18) and healthy controls matched for age and sex (n=18). Thrombin generation (TG) was measured in whole blood (WB) and plasma. The capacity of platelets to release granules (PGRC) was measured in WB. We explored the occurrence of thromboembolic events in PDAC patients during 6-months follow-up. RESULTS: Patients showed an increased endogenous thrombin potential (ETP) in WB, compared to controls. This difference was not observed in plasma, indicating a procoagulant effect of blood cells. Both in WB and plasma, the lag time was prolonged in patients compared to controls. Patients had hyperresponsive platelets, with a shorter time to peak granule release. Of the 18 PDAC patients, four developed a VTE (22%) and one an ATE (6%). A shorter lag time in whole blood, not in plasma, and an increased PGRC were associated with thromboembolic events. CONCLUSIONS: Patients with PDAC have an increased and delayed WB-TG coagulation profile compared to controls. A shorter lag time in WB-TG and increased PGRC associated with the incidence of thromboembolic events. Platelets appear to be key players in thrombosis development. Measuring hemostasis in whole blood could improve thrombosis risk estimation in PDAC patients.