PB1447 - Closer Examination of Venous Thromboembolism in Colorectal Cancer Patients

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

Dongyue Fan, MA

PhD student
Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
MY

Monika Yanovska

Research Intern
SciLifeLab
Leiden, Zuid-Holland, Netherlands
Nick van Es, MD PhD

Internist-vascular medicine
Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands
Amsterdam, Noord-Holland, Netherlands
Mettine H.A Bos, PhD

PhD
Dept. Internal Medicine, Div. Thrombosis and Hemostasis, Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
JB

Jeroen Buijs

Senior researcher
Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
AR

Araci M.R. Rondon

Postdoctoral researcher
Einthoven Laboratory for Vascular and Regenerative Medicine, section Thrombosis and Hemostasis, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Leiden, Zuid-Holland, Netherlands

Presenting Author(s)

Henri Versteeg, PhD

Professor
Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands

Background: Venous thromboembolism (VTE) is a critical factor that contributes to poor prognosis and it is an important cause of mortality in cancer patients. Colorectal cancer (CRC) patients are at increased risk of VTE. Currently, there is still a lack of understanding of which mechanisms are involved in VTE in CRC-associated VTE.

Aims: Employ a multifaceted approach to unravel the biological mechanisms underlying VTE in CRC patients.

Methods: An organ-on-a-chip model was established to mimic CRC-associated thrombosis. The endothelial permeability and thrombin generation were evaluated. 18 CRC blood plasma samples and 8 with previous VTE were analyzed by Tissue Factor Enzyme-Linked Immunosorbent Assay and Thrombin Generation Assay. Furthermore, we incubated CRC patient plasma in the organ-on-a-chip model for thrombin generation assay.

Results: The presence of colorectal tumor spheroids reduced by 50% the barrier integrity of endothelial cell-based vessels, and the endogenous thrombin potential (ETP) was increased 10-fold in the chip compared to the control group (only endothelial vessels). The median levels of plasma tissue factor in CRC patients plasma without VTE and with VTE were 29.7 pg/mL and 29.88 pg/mL, respectively. The median levels of plasma ETP in CRC patients without VTE and with VTE were 2235.33 nM.min and 2088.56 nM.min (P=0.8759), respectively. Thrombin generation assay performed in the organ-on-a-chip model showed that the median levels of plasma ETP in CRC patients without and with VTE were 488.8 nM.min and 439.7 nM.min (P =0.8455), respectively.

Conclusion(s): The organ-on-a-chip model showed that the co-culture with colorectal tumor spheroids reduced endothelial permeability and increased the formation of thrombin inside the vessel. However, in clinical sampling experiments, there was no significant difference in TF concentration or thrombin formation between CRC patients with VTE and without VTE. We conclude that TF does not play a role in CRC-associated VTE.