Differing mechanisms of thrombin generation in live haematological and solid cancer cells determined by calibrated automated thrombography

Adesanya, Mufuliat Adeola; Maraveyas, Anthony; Madden, Leigh

Abstract

© 2017 Wolters Kluwer Health, Inc. All rights reserved. Calibrated automated thrombography (CAT) is emerging as a reliable tool for real-Time estimation of thrombin generation potential. There is a clinical need for knowledge about the pathways underlying the thrombotic phenotype of different malignancies. Cells from solid (e.g. pancreatic cancer; n = 7) and malignant haematological cell lines (e.g. multiple myeloma; n = 5) were evaluated for thrombin generation, using CAT, with the addition of control plasma (NormTrol; Helena Biosciences, Gateshead, UK)) or plasma deficient in coagulation factors VII and XII. In addition, tissue factor (TF) cell surface expression was determined by flow cytometry. In platelet-free plasma, thrombin generation in all cancer cell lines was cell concentration dependent, with the pancreatic cancer line CFPAC-1 producing the highest thrombin of 220 nmol/l at 5 × 10 6-cells/ml concentration. Lag times and times to peak reflected most significant differences out of all thrombin generation parameters measured and were inversely correlated with cell surface TF surface expression. Solid tumour cell lines had higher thrombin peaks, faster lag times, and a thrombin generation profile of overall greater magnitude than haematological cell lines. In the absence of factor VII in platelet-free plasma, thrombin generation in solid pancreatic cancer cell lines was significantly reduced unlike in haematological cell lines. However, in the absence of factor XII, thrombin generation was reduced more in haematological cells but had little or no effect on solid cell lines. The CAT assay identified characteristic differences in thrombin generation kinetics between solid tumour and haematological cancer cell lines, of which lag time and time to peak correlated with TF cell surface expression.

Citation

Adesanya, M. A., Maraveyas, A., & Madden, L. (2017). Differing mechanisms of thrombin generation in live haematological and solid cancer cells determined by calibrated automated thrombography. Blood Coagulation and Fibrinolysis, 28(8), 602-611. https://doi.org/10.1097/mbc.0000000000000644

• Journal Article Type: Article
• Acceptance Date: Jun 4, 2017
• Publication Date: Dec 1, 2017
• Deposit Date: Dec 18, 2017
• Publicly Available Date: Dec 2, 2018
• Journal: Blood Coagulation & Fibrinolysis
• Print ISSN: 0957-5235
• Publisher: Lippincott, Williams & Wilkins
• Peer Reviewed: Peer Reviewed
• Volume: 28
• Issue: 8
• Pages: 602-611
• DOI: https://doi.org/10.1097/mbc.0000000000000644
• Keywords: Hematology; General Medicine
• Public URL: https://hull-repository.worktribe.com/output/504639
• Publisher URL: http://journals.lww.com/bloodcoagulation/Citation/2017/12000/Differing_mechanisms_of_thrombin_generation_in.3.aspx
• Contract Date: Dec 19, 2017