Factor XI activity in ST-segment elevation myocardial infarction
Authors: Spagnolo M , Di Leo G , Ammirabile N , Finocchiaro S , Giacoppo D , Greco A , Imbesi A , Landolina D , Laudani C , Mauro M S , Mazzone P M , Tamburino C , Capodanno D 
Published: October 2024

Abstract

Background
ST-segment elevation myocardial infarction (STEMI) is characterized by a significant thrombotic burden, where the coagulation cascade, including Factor XI (FXI) activity, plays a crucial role. In STEMI and other thrombotic conditions, FXI levels vary according to patient characteristics and timing from the event. Understanding the changes in FXI activity may offer valuable insights into the optimal patient selection and timing for use of investigational FXI inhibitors.

Purpose
Our aim was to characterize variations in FXI activity in STEMI patients.

Methods
In this prospective, observational study, patients admitted with STEMI underwent two measurements of plasma FXI activity, prior to coronary angiography and at discharge, using the HemosIL assay. The variation in FXI activity at these timepoints was compared between patients with and without coronary thrombus, as detected by an angiographic core-lab. Linear regression analyses were conducted to test the association of candidate predictors with FXI variation between admission and discharge (i.e., presence of coronary thrombus, PCI of the culprit artery, Thrombolysis in Myocardial Infarction flow post-PCI, bailout use of glycoprotein IIb/IIIa inhibitors, time to second measurement of FXI activity) and with FXI value at admission (i.e., age, sex, atrial fibrillation, late [&gt;24 hours] STEMI presentation, presence of coronary thrombus).

Results
From November 2023 to February 2024, 49 STEMI patients were included. The median variation in FXI activity among admission and discharge was +24.8% (interquartile range [IQR] 11.8; 69.0; p&lt;0.001). This variation was observed in both patients with (+41.6% [IQR 14.3; 74.6]; p&lt;0.001) and without (+21.8% [IQR -2.3;40.7]; p=0.008) thrombus at coronary angiography, with significant interaction effects compared to the global STEMI population (p for interaction &lt;0.001). An inverse linear regression relationship was observed between presence of coronary thrombus and changes in FXI activity (coefficient -33.0, 95% CI -59.5 to -7.2; p=0.012). Furthermore, in the model exploring predictors of FXI activity at admission, thrombus presence (coefficient -40.9, 95% CI -75.3 to -6.4; p=0.024) and subacute presentation (coefficient 90.8, 95% CI 21.9 to 159.8; p=0.015) emerged as significant predictors, albeit with contrasting effects on FXI activity. Figure 1

Conclusions
Our findings reveal significant increases in FXI activity from admission to discharge in STEMI patients. The inverse relationship between the presence of coronary thrombus and FXI activity variations, along with the contrasting associations among initial FXI levels and subacute patients’ presentation or thrombus presence, support the importance of FXI in the coagulation process during STEMI. These findings suggest targeted FXI inhibition, especially early in STEMI management, could be beneficial, meriting detailed investigation in future studies.Multivariable linear regression analysis