Fractal dimension (df) as a new structural biomarker of clot microstructure in different stages of lung cancer

Nia Anne Davies; Nicholas Kim Harrison; Roger H. Keith Morris; Simon Noble; Matthew James Lawrence; Lindsay Antonio D’Silva; Laura Broome; Martin Rowan Brown; Karl M. Hawkins; Phylip Rhodri Williams; Simon Davidson; Phillip Adrian Evans

doi:10.1160/TH15-04-0357

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2015; 114(06): 1251-1259
DOI: 10.1160/TH15-04-0357

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Fractal dimension (d_f ) as a new structural biomarker of clot microstructure in different stages of lung cancer

Nia Anne Davies

¹College of Medicine, Swansea University, Swansea, UK

²NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, UK

,

Nicholas Kim Harrison

¹College of Medicine, Swansea University, Swansea, UK

³Respiratory Unit, Morriston Hospital, ABMU Health Board, Swansea, UK

,

Roger H. Keith Morris

⁴School of Applied Science, Cardiff Metropolitan University, Cardiff, UK

,

Simon Noble

⁵School of Medicine, Cardiff University, Cardiff, UK

,

Matthew James Lawrence

¹College of Medicine, Swansea University, Swansea, UK

²NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, UK

,

Lindsay Antonio D’Silva

¹College of Medicine, Swansea University, Swansea, UK

²NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, UK

,

Laura Broome

¹College of Medicine, Swansea University, Swansea, UK

²NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, UK

,

Martin Rowan Brown

⁶College of Engineering, Swansea University, Swansea, UK

,

Karl M. Hawkins

¹College of Medicine, Swansea University, Swansea, UK

,

Phylip Rhodri Williams

⁶College of Engineering, Swansea University, Swansea, UK

,

Simon Davidson

⁷Department of Haematology, Royal Brompton Hospital, Royal Brompton and Harefield NHS Foundation Trust, London, UK

,

Phillip Adrian Evans

¹College of Medicine, Swansea University, Swansea, UK

²NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, UK

› Author Affiliations

Abstract

Summary

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 (d_f) 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 d_f 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 d_f 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 d_f of the incipient clot and mature clot microstructure was confirmed by SEM and computational modelling: higher d_f was associated with highly dense clots formed of smaller fibrin fibres in lung cancer patients compared to controls. This study demonstrates that d_f is a sensitive technique which quantifies the structure and mechanical properties of blood clots in patients with lung cancer. Our data suggests that d_f has the potential to identify patients with an abnormal clot micro-structure and greatest VTE risk.

Keywords

Lung cancer - venous thromboembolism - risk assessment - biomarker - fractal

Full Text

References

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Fractal dimension (df ) as a new structural biomarker of clot microstructure in different stages of lung cancer

Fractal dimension (d_f ) as a new structural biomarker of clot microstructure in different stages of lung cancer