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Semin Thromb Hemost 2024; 50(03): 384-401
DOI: 10.1055/s-0043-1775856
Review Article

Thrombin Generation Markers as Predictors of Cancer-Associated Venous Thromboembolism: A Systematic Review

Tua Gyldenholm
1   Department of Clinical Biochemistry, Thrombosis and Haemostasis Research Unit, Aarhus University Hospital, Aarhus, Denmark
2   Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
,
Anne-Mette Hvas
3   Faculty of Health, Aarhus University, Aarhus, Denmark
,
Thomas Decker Christensen
2   Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
4   Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark
,
Julie Brogaard Larsen
1   Department of Clinical Biochemistry, Thrombosis and Haemostasis Research Unit, Aarhus University Hospital, Aarhus, Denmark
2   Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
› Author Affiliations Funding TG: PhD scholarship from Aarhus University, Aarhus, Denmark.
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Abstract

Venous thromboembolism (VTE) is a main contributor to morbidity and mortality in cancer patients. Biomarkers with the potential to predict cancer-associated VTE are continually sought. Of these, markers of thrombin generation present a likely option. The present systematic review examines the ability of three widely used biomarkers of thrombin generation: prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT), and ex vivo thrombin generation, to predict VTE in both solid and hematologic adult cancer patients. Relevant studies were identified in the PubMed and Embase databases, and the review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Each study was evaluated using the quality assessment tool from the National Heart, Lung, and Blood Institute. The review protocol was published on PROSPERO with identifier CRD42022362339. In total, 24 papers were included in the review: 11 reporting data on F1.2, 9 on TAT, and 12 on ex vivo thrombin generation. The quality ratings of the included studies varied from good (n = 13), fair (n = 8), to poor (n = 3) with a high heterogenicity. However, F1.2, TAT complex, and ex vivo thrombin generation were all found to be associated with the development of VTE. This association was most pronounced for F1.2. Furthermore, the determination of F1.2 was able to improve the precision of several established risk assessment scores. In conclusion, markers of thrombin generation were found to be elevated in cancer patients with VTE, and particularly, F1.2 was found to be a promising predictor of cancer-associated VTE.

Keywords

prothrombin fragment 1.2 - antithrombin III-protease complex - thrombin generation - cancer-associated thrombosis - embolism and thrombosis - neoplasms


Publication History

Article published online:
09 October 2023

© 2023. Thieme. All rights reserved.

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