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

TY - JOUR

T1 - Thrombin Generation Markers as Predictors of Cancer-Associated Venous Thromboembolism

T2 - A Systematic Review

AU - Gyldenholm, Tua

AU - Hvas, Anne-Mette

AU - Christensen, Thomas Decker

AU - Larsen, Julie Brogaard

N1 - Thieme. All rights reserved.

PY - 2024/4

Y1 - 2024/4

N2 - 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.

AB - 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.

KW - antithrombin III-protease complex

KW - cancer-associated thrombosis

KW - embolism and thrombosis

KW - neoplasms

KW - prothrombin fragment 1.2

KW - thrombin generation

KW - Humans

KW - Risk Factors

KW - Thrombin

KW - Venous Thromboembolism/diagnosis

KW - Biomarkers

KW - Adult

KW - Neoplasms/complications

U2 - 10.1055/s-0043-1775856

DO - 10.1055/s-0043-1775856

M3 - Review

C2 - 37813372

SN - 0094-6176

VL - 50

SP - 384

EP - 401

JO - Seminars in Thrombosis and Hemostasis

JF - Seminars in Thrombosis and Hemostasis

IS - 3

ER -