An ex vivo study on the hypercoagulability of brain cancer patients at an academic hospital by studying the morphological and viscoelastic properties of platelet-poor plasma

Abstract

Cancer and its associated outcomes rank among the primary contributors to global mortality. Tumour cells are not only able to alter their cellular physiology to promote their own growth but can also disrupt the coagulation system by interfering with natural signals and pathways in the body, particularly the inflammatory and coagulation pathways. As a result, about 20% of brain cancer patients suffer complications associated with coagulopathies. Extensive research is required to understand the coagulation potential in brain cancer patients and identify the factors that trigger hypercoagulation in these patients. This study aimed to investigate the potential hypercoagulable state in brain cancer patients at an academic hospital, comparing them to healthy individuals by studying the morphological and viscoelastic properties of platelet-poor plasma (PPP), specifically focusing on fibrin formation. This study measured the viscoelastic properties of PPP during clot formation using Thromboelastography®. Additionally, scanning electron microscopy was employed to analyse and compare the clot ultrastructural morphology of fibrin networks between patients and healthy individuals. The fibrin fibre thicknesses of both groups were then measured and compared using the ImageJ software. Branching of the fibrin fibres was measured by determining the fractal dimensions from the scanning electron microscope images with Fractalyse software. Clinical tests—including the international normalised ratio (INR), C-reactive protein (CRP), and procalcitonin tests (PCT)—were obtained from patient records and used to create a clinical profile of the patient population. These values were compared to healthy reference ranges to identify any potential abnormalities in the patient group. The INR was used to determine the time it took for the patients’ blood to clot, whereas the CRP and PCT were used to evaluate their inflammatory status. The clinical tests showed normal INR and PCT values but elevated CRP values when compared to normal ranges. This indicated that the brain cancer patients in this study exhibited normal clotting times and no signs of bacterial infection. The elevated CRP values could be indicative of elevated inflammation caused by the brain cancer. The viscoelastic and ultrastructural results showed that there were no significant differences in any of the analyses between the healthy individuals and those with brain cancer, except with regards to the fibre thickness. Specifically, this study found that brain cancer patients have thinner fibrin fibres than healthy individuals. Thinner fibres exhibit a reduced rate of dissolution compared to thicker fibres, resulting in the persistence of clots and, consequently, increasing the patient's susceptibility to thrombotic events. The results from this study open avenues to further study the impact of brain cancer on the formation of fibrin fibres during clot formation. While the tests used in this study might not have been sensitive enough to identify subclinical changes, future tests measuring fibrinogen levels, coagulation factors, and clot lysis could provide valuable insights into how coagulation is affected in these patients. Such insights might reveal potential targets for more effective patient management.