title: Fractal dimension (df) as a new structural biomarker of clot microstructure in different stages of lung cancer.
abstract: Venous thromboembolism (VTE) is common in cancer patients, and is the second commonest cause of death associated with the disease. Patients with chronic inflammation, such as cancer, have been shown to have pathological clot structures with modulated mechanical properties. Fractal dimension (df) is a new technique which has been shown to act as a marker of the microstructure and mechanical properties of blood clots, and can be performed more readily than current methods such as scanning electron microscopy (SEM). We measured df in 87 consecutive patients with newly diagnosed lung cancer prior to treatment and 47 matched-controls. Mean group values were compared for all patients with lung cancer vs controls and for limited disease vs extensive disease. Results were compared with conventional markers of coagulation, fibrinolysis and SEM images. Significantly higher values of df were observed in lung cancer patients compared with controls and patients with extensive disease had higher values than those with limited disease (p< 0.05), whilst conventional markers failed to distinguish between these groups. The relationship between df of the incipient clot and mature clot microstructure was confirmed by SEM and computational modelling: higher df was associated with highly dense clots formed of smaller fibrin fibres in lung cancer patients compared to controls. This study demonstrates that df is a sensitive technique which quantifies the structure and mechanical properties of blood clots in patients with lung cancer. Our data suggests that df has the potential to identify patients with an abnormal clot microstructure and greatest VTE risk.
authors: Nia Anne
authors: NA
authors: Davies
authors: Nicholas Kim
authors: NK
authors: Harrison
authors: Roger H Keith
authors: RH
authors: Morris
authors: Simon
authors: S
authors: Noble
authors: Matthew James
authors: MJ
authors: Lawrence
authors: Lindsay Antonio
authors: LA
authors: D'Silva
authors: Laura
authors: L
authors: Broome
authors: Martin Rowan
authors: MR
authors: Brown
authors: Karl M
authors: KM
authors: Hawkins
authors: Phylip Rhodri
authors: PR
authors: Williams
authors: Simon
authors: S
authors: Davidson
authors: Prof. Phillip Adrian Evans, Director, NISCHR Haemostasis Biomedical Research Unit, Abertawe Bro Morgannwg University Health Board, NISCHR Haemostasis Biomedical Research Unit, Emergency Department, Morriston Hospital Abertawe Bro Morgannwg University Health Board, Swansea, UK, SA6 6NL, Tel.: +44 1792 703418, E-mail: phillip.evans2@wales.nhs.uk.
authors: Phillip Adrian
authors: PA
authors: Evans
mesh_terms: D000368:Aged; D000465:Algorithms; D015415:Biomarkers; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000150:complications / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000097:blood* / Q000150:complications / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005337:Fibrin / Q000648:ultrastructure; D017709:Fractals; D018056:Hemorheology; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000150:complications / Q000473:pathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D012306:Risk; D016037:Single-Blind Method; D012907:Smoking / Q000097:blood; D019851:Thrombophilia / Q000097:blood* / Q000209:etiology; D054556:Venous Thromboembolism / Q000097:blood / Q000209:etiology
chemical_list: D015415:Biomarkers; D005337:Fibrin
keywords: Lung cancer; biomarker; fractal; risk assessment; venous thromboembolism