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Semin Thromb Hemost 2024; 50(03): 429-442
DOI: 10.1055/s-0043-1777304
Review Article

Cellular Components Contributing to the Development of Venous Thrombosis in Patients with Pancreatic Cancer

Ruth Anne Laura Willems   *
1   Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands
2   Thrombosis Expert Center Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
3   Division of Vascular Medicine, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
4   Division of Medical Oncology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
5   CARIM, School for Cardiovascular Diseases, Maastricht, The Netherlands
,
Charlotte Biesmans   *
1   Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands
2   Thrombosis Expert Center Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
3   Division of Vascular Medicine, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
4   Division of Medical Oncology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
,
Elena Campello
6   General Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine - DIMED, University of Padova, Padova, Italy
,
Paolo Simioni
6   General Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine - DIMED, University of Padova, Padova, Italy
,
Bas de Laat
1   Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands
5   CARIM, School for Cardiovascular Diseases, Maastricht, The Netherlands
7   Department of Platelet Pathophysiology, Synapse Research Institute, Maastricht, The Netherlands
,
Judith de Vos-Geelen
4   Division of Medical Oncology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
8   GROW, Maastricht University Medical Center, Maastricht, The Netherlands
,
Mark Roest
7   Department of Platelet Pathophysiology, Synapse Research Institute, Maastricht, The Netherlands
,
Hugo ten Cate
2   Thrombosis Expert Center Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
3   Division of Vascular Medicine, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
5   CARIM, School for Cardiovascular Diseases, Maastricht, The Netherlands
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of cancer and has a poor prognosis. Patients with PDAC are at high risk of developing thromboembolic events, which is a leading cause of morbidity and mortality following cancer progression. Plasma-derived coagulation is the most studied process in cancer-associated thrombosis. Other blood components, such as platelets, red blood cells, and white blood cells, have been gaining less attention. This narrative review addresses the literature on the role of cellular components in the development of venous thromboembolism (VTE) in patients with PDAC. Blood cells seem to play an important role in the development of VTE. Altered blood cell counts, i.e., leukocytosis, thrombocytosis, and anemia, have been found to associate with VTE risk. Tumor-related activation of leukocytes leads to the release of tissue factor-expressing microvesicles and the formation of neutrophil extracellular traps, initiating coagulation and forming a scaffold for thrombi. Tissue factor-expressing microvesicles are also thought to be released by PDAC cells. PDAC cells have been shown to stimulate platelet activation and aggregation, proposedly via the secretion of podoplanin and mucins. Hypofibrinolysis, partially explained by increased plasminogen activator inhibitor-1 activity, is observed in PDAC. In short, PDAC-associated hypercoagulability is a complex and multifactorial process. A better understanding of cellular contributions to hypercoagulability might lead to the improvement of diagnostic tests to identify PDAC patients at highest risk of VTE.

Keywords

pancreatic ductal adenocarcinoma - cancer-associated thrombosis - venous thromboembolism - red blood cells - platelets - white blood cells

* Contributed equally and joint first authors.




Publication History

Article published online:
04 December 2023

© 2023. Thieme. All rights reserved.

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