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Altered whole blood thrombin generation and hyperresponsive platelets in patients with pancreatic cancer
Ruth Anne Laura Willems1, Joke Konings2, Dana Huskens2
1Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands; Thrombosis Expert Center Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Internal Medicine, Division of Vascular Medicine, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Internal Medicine, Division of Medical Oncology, Maastricht University Medical Center, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht (CARIM), School for Cardiovascular Diseases, Maastricht, The Netherlands.
Background:
Thromboembolic disease is a major complication in patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often have altered blood cell counts, which are associated with venous thromboembolism (VTE) development. The high thrombotic risk in patients with PDAC may be partially caused by procoagulant blood cells.
Objectives:
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).
Methods:
Thrombin generation (TG) was measured in whole blood (WB) and plasma. The capacity of platelets to release granules (PGRCs) was measured in WB. We explored the occurrence of thromboembolic events in patients with PDAC during a 6-month follow-up.
Results:
Patients showed an increased endogenous thrombin potential in WB compared with 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 with controls. Patients had hyperresponsive platelets, with a shorter time to peak granule release. Of the 18 patients with PDAC, 4 developed a venous thromboembolism (22%) and 1 developed an arterial thrombosis (6%). A shorter lag time in WB, but not in plasma, and an increased PGRC were associated with thromboembolic events.
Conclusion:
Patients with PDAC have an increased and delayed WB TG coagulation profile compared with controls. A shorter lag time in WB TG and increased PGRC are associated with the incidence of thromboembolic events. Platelets appear to be key players in thrombosis development. Measuring hemostasis in WB could improve thrombosis risk estimation in patients with PDAC.
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