OC 51.4 - Low thrombin inactivation capacity is an independent risk factor for cancer mortality in men: results from the Moli-sani study

Tuesday, June 27, 2023

11:30 – 11:45 ET

Room: 710A

Session Available As: On-Demand

Presenting Author(s)

Romy De Laat-Kremers, PhD

Post-doctoral Research Project Leader
Department of Data Analysis and Artificial Intelligence, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands

Co-Author(s)

SC

Simona Costanzo

Senior Researcher
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, IS, Italy
Pozzilli, Molise, Italy
AD

Augusto Di Castelnuovo

Senior Researcher
Mediterranea Cardiocentro, Napoli, Italy
Napoli, Campania, Italy
QY

Qiuting Yan

.
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
SM

Sara Magnacca

.
Mediterranea Cardiocentro, Napoli, Italy
Napoli, Campania, Italy
MD

Maria Benedetta Donati

Senior Researcher
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy
Pozzilli, Molise, Italy
Bd

Bas de Laat, MD, PhD

General Director
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
LI

Licia Iacoviello

.
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy
Pozzilli, Molise, Italy

Background: Cancer-associated thrombosis is a frequent complication provoked by the tumor or treatment. Key coagulation enzyme thrombin is naturally inhibited by antithrombin (AT) and α2-macroglobulin (α2M). Low AT levels and high fibrinogen levels are a known risk factor for mortality in certain cancer patient populations. The thrombin decay capacity (TDC) quantifies the natural ability to inhibit thrombin by AT and α2M, and the interference of fibrinogen.

Aims: To investigate whether TDC is a predictor of cancer mortality in a general adult population.

Methods: We studied the association of TDC and cancer mortality in a prospective general Italian cohort of the Moli-sani study (n=18,701). Blood was drawn at the baseline visit and (cancer) mortality was recorded during a median follow-up period of 8.2 years. Anticoagulated subjects were excluded from analysis. AT, α2M, fibrinogen and TDC were determined at baseline. The association of cancer mortality and TDC was assessed by Cox regression.

Results: Cancer mortality was higher in the lowest TDC percentiles, regardless of cancer history (Figure 1). Low TDC was significantly associated with cancer mortality after adjustment for age, sex, body mass index, oral contraceptives, hypertension, hypercholesterolemia, and cardiovascular diseases and history of cancer (p < 0.001). Subjects in the lowest percentile of TDC had a HR of 3.22 (95% CI:1.87-5.55, p< 0.001, Figure 2). Men in the lowest percentile of TDC had a HR of 3.44 for cancer mortality (95% CI:1.94-6.12, p< 0.001), whereas women did not. Cancer history did not affect the association between TDC and cancer mortality, albeit that low TDC and cancer mortality are significantly associated in women and men with a cancer history (HR:3.81; 95%CI:1.13-12.9, p=0.035 vs. HR:3.58; 95% CI:1.21-10.6, p=0.021).

Conclusion(s): Decreased thrombin inactivation is associated with increased mortality in cancer patients. Interestingly, decreased thrombin inactivation before the diagnosis of cancer is also associated with cancer mortality, but only in men.

Learning Objectives:

Discuss how the thrombin is produced and inactivation during coagulation, and to recognize the coagulation factors that influence thrombin inactivation during coagulation.
Evaluate the thrombin inactivation capacity as a risk factor for cancer mortality in the general population.
Differentiate between the cancer-related mortality risk associated with a low thrombin inactivation capacity in men and women, respectively.