From Physiology to Clinical Practice in Pancreatic Cancer-Related Thromboembolism—A Review

TL;DR

This review explores the mechanisms and management of blood clots in pancreatic cancer patients, highlighting challenges and treatment options.

Contribution

The paper provides a comprehensive overview of thromboembolism mechanisms and current treatment strategies in pancreatic cancer.

Findings

Pancreatic cancer has the highest rate of thromboembolic complications among solid tumors.

Tumor-derived factors and the tumor microenvironment contribute to hypercoagulability in pancreatic cancer.

Low molecular weight heparin and direct oral anticoagulants are key treatments for managing venous thromboembolism in these patients.

Abstract

Pancreatic cancer (PC) is a common and highly lethal solid tumor with rising incidence and mortality rates. The most common type of PC is pancreatic ductal adenocarcinoma, which has the highest incidence of thromboembolic complications of all malignant tumors. These events, particularly deep vein thrombosis and pulmonary embolism, are associated with increased mortality during the course of the disease. This review summarizes tumor- and microenvironment-driven mechanisms of thromboembolism in PC and highlights key risk factors related to the disease, patient characteristics, and treatment modalities. It also outlines warning signs that require further diagnostic evaluation and summarizes diagnostic methods, treatment options, and preventive measures. Finally, the review identifies deficiencies in the management of thromboembolic complications in PC patients and presents ongoing research aimed at improving patient care.

Pancreatic cancer (PC) is a highly lethal malignancy linked to the highest rate of thromboembolic complications (TEC) among all solid tumors. TECs occur in approximately 5–40% of PC patients. The most common type of TEC in PC is venous thromboembolism (VTE). The mechanisms leading to frequent TEC in PC are complex and involve interactions between tumor-derived procoagulant factors and the prothrombotic tumor microenvironment (TME). Secretion of tissue factor and proinflammatory cytokines by tumor cells and the TME, overexpression of heparanase and podoplanin, impaired fibrynolysis and increased neutrophil extracellular trap formation lead to platelet hyperactivation resulting in hypercoagulability in PC. Understanding these mechanisms is crucial for identifying risk factors of TEC. Current thromboembolism risk models have limited predictive accuracy, which reduces their clinical usefulness. Identifying patients with thromboembolism is challenging because these events are often asymptomatic and their clinical presentation varies depending on the location of the thrombus. Treatment of VTE in PC depends on the phase of the VTE; in the acute phase, treatment primarily involves LMWH. For long-term management, LMWH may be replaced by direct oral anticoagulants such as apixaban, edoxaban, or rivaroxaban. In cases of VTE recurrence, increasing the LMWH dose, switching to an oral anticoagulant, or placing an inferior vena cava filter should be considered. LWMH and unfractionated heparin (UFH) are preferred options for VTE prophylaxis. Novel therapies, including factor XI inhibitors, show efficacy comparable to LMWH while offering a better safety profile.

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