# The Clinical Utility of Selected Coagulation Parameters in Predicting the Risk of Venous Thromboembolism in Neuroendocrine Tumours: A Prospective, Single-Centre Study

## TL;DR

This study explores how coagulation parameters like D-dimer and fibrinogen can help predict venous thromboembolism risk in patients with neuroendocrine tumors.

## Contribution

This is the first prospective study evaluating coagulation parameters and VTE risk assessment models in neuroendocrine tumors.

## Key findings

- D-dimer levels were significantly higher in neuroendocrine tumor patients compared to healthy controls.
- Higher Khorana and Vienna CATS scores were associated with worse survival in these patients.
- D-dimer and fibrinogen levels were elevated in patients with disease progression.

## Abstract

Neuroendocrine tumours (NETs) belong to a heterogeneous group of malignant neoplasms that differ in their ability to produce hormones and biogenic amines, which is often associated with a more favourable prognosis for well-differentiated tumours. Despite numerous reports in the literature documenting venous thromboembolism (VTE) events in these patients, data on thromboembolic complications in NETs remain limited, and no specific recommendations exist regarding the use of antithrombotic prophylaxis in this group. Thrombotic risk assessment models have not yet been validated in NETs. This article presents the first prospective analysis of selected coagulation parameters, the incidence and risk factors for VTE, and evaluates thromboembolic risk assessment models as well as survival data in pancreatic and small intestinal NETs. Our aim was to improve patient stratification for VTE risk and to help identify patients with NETs who might benefit from antithrombotic prophylaxis.

Background: Data on venous thromboembolism (VTE) in neuroendocrine tumours (NETs) are scarce. To the best of our knowledge, this is the first analysis of coagulation parameters and a comparison of VTE risk assessment scales in NETs. Methods: Patients with well-differentiated NETs (n = 99), including pancreatic (n = 63) and small intestinal (n = 36) primary, as well as 47 healthy controls, were enrolled. Blood levels of coagulation parameters, including D-dimer (DD), fibrinogen, platelets, antithrombin III (AT-III), and tissue factor (TF), were assessed. Venous Doppler ultrasound of the lower extremities was performed in all study participants. Results: DD plasma concentration was significantly higher in NET patients than in the control group (957.59 ± 2021.86 µg/L vs. 400.26 ± 230.55 µg/L, p = 0.007) and positively correlated with chromogranin A (rS = 0.32, p = 0.001). DD and fibrinogen plasma levels were statistically higher in patients with disease progression compared to those with stable disease (2513.7 ± 3624.3 vs. 431.9 ± 244.7 µg/L, p < 0.001; 359.3 mg/mL vs. 305.4 mg/mL, p < 0.001, respectively). None of the VTE risk assessment scales provided a good measure (AUC > 0.7) in ROC analysis. However, higher scores on the Khorana (p = 0.023) and Vienna CATS scale (p < 0.001) were associated with unfavourable survival in NETs. Conclusions: Pancreatic NETs demonstrate increased risk of VTE. The Khorana and Vienna CATS scales best correlated with the NET patients’ outcomes. Routine assessment of DD and fibrinogen may improve risk stratification for VTE in NET patients; however, extensive multicenter validation is necessary for clinical implementation.