Changes in Coagulation Factor XI Activity Levels in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI

Abstract

Background Although factor XI (FXI) inhibitors are currently tested for the prevention of thrombotic events, their early treatment could prevent thrombus consolidation in ST-segment elevation myocardial infarction (STEMI). This study aims to characterize coagulation FXI levels and their variations in patients with STEMI undergoing primary percutaneous coronary intervention (PCI).

Methods Patients with STEMI were prospectively enrolled between December 2023 and May 2024. FXI activity (FXIa) levels were measured at admission and after PCI (i.e., before discharge). Variations in FXIa levels were evaluated. Differences in indicators of thrombotic risk between groups with high and low FXIa variability were analyzed, and predictors of high FXIa variability were identified.

Results After screening, 54 patients with STEMI were included. The median FXIa level was 0.865 IU/mL (interquartile range [IQR] 0.554–0.978) at admission and 1.161 IU/mL (IQR 0.982–1.317) before discharge, with a median difference of +34.2% (p-value < 0.001). No significant differences were found in indicators of thrombotic risk between groups at high and low FXIa variability, except for the days intercurred between the assays (p-value = 0.016). Neither this nor other variables emerged as independent predictors of high FXIa variability.

Conclusion This study first reported an increase in FXIa levels from admission to discharge in STEMI patients undergoing PCI. Common indicators of thrombotic risk were not associated with FXIa levels or their variability. These findings aim to stimulate further research into anticoagulant therapies tailored to the patient's coagulative state and disease.

Keywords

factor XI - factor XI inhibitors - ST-segment elevation myocardial infarction - percutaneous coronary intervention - anticoagulants

• References

• 1 Vogel B, Claessen BE, Arnold SV. et al. ST-segment elevation myocardial infarction. Nat Rev Dis Primers 2019; 5 (01) 39
• 2 Byrne RA, Rossello X, Coughlan JJ. et al; ESC Scientific Document Group. 2023 ESC guidelines for the management of acute coronary syndromes. Eur Heart J 2023; 44 (38) 3720-3826
• 3 Greco A, Laudani C, Spagnolo M. et al. Pharmacology and clinical development of factor XI inhibitors. Circulation 2023; 147 (11) 897-913
• 4 Occhipinti G, Laudani C, Spagnolo M. et al. Pharmacological and clinical appraisal of factor XI inhibitor drugs. Eur Heart J Cardiovasc Pharmacother 2024; 10 (03) 245-258
• 5 Raffo C, Capodanno D. Factor XI inhibition in patients with acute coronary syndrome. Eur Heart J Suppl 2024; 26 (Suppl. 01) i29-i34
• 6 Kyrle PA, Eischer L, Šinkovec H, Eichinger S. Factor XI and recurrent venous thrombosis: an observational cohort study. J Thromb Haemost 2019; 17 (05) 782-786
• 7 Meijers JC, Tekelenburg WL, Bouma BN, Bertina RM, Rosendaal FR. High levels of coagulation factor XI as a risk factor for venous thrombosis. N Engl J Med 2000; 342 (10) 696-701
• 8 Gill D, Georgakis MK, Laffan M. et al. Genetically determined FXI (factor XI) levels and risk of stroke. Stroke 2018; 49 (11) 2761-2763
• 9 Rohmann JL, Huo S, Sperber PS. et al. Coagulation factor XII, XI, and VIII activity levels and secondary events after first ischemic stroke. J Thromb Haemost 2020; 18 (12) 3316-3324
• 10 Chen H, Shen M, Niu R. et al. Associations of coagulation factor X and XI with incident acute coronary syndrome and stroke: a nested case-control study. J Thromb Haemost 2021; 19 (11) 2781-2790
• 11 Nagy M, Robles AP, Visser M. et al. Predictive value for increased activated factor XI activity in acute venous thromboembolism. J Thromb Haemost 2023; 21 (06) 1610-1622
• 12 Loeffen R, van Oerle R, de Groot PG. et al. Increased factor XIa levels in patients with a first acute myocardial infarction: the introduction of a new thrombin generation based factor XIa assay. Thromb Res 2014; 134 (06) 1328-1334
• 13 Attard C, van der Straaten T, Karlaftis V, Monagle P, Ignjatovic V. Developmental hemostasis: age-specific differences in the levels of hemostatic proteins. J Thromb Haemost 2013; 11 (10) 1850-1854
• 14 Loeffen R, van Oerle R, Leers MP. et al. Factor XIa and thrombin generation are elevated in patients with acute coronary syndrome and predict recurrent cardiovascular events. PLoS One 2016; 11 (07) e0158355
• 15 Kadir RA, Economides DL, Sabin CA, Owens D, Lee CA. Variations in coagulation factors in women: effects of age, ethnicity, menstrual cycle and combined oral contraceptive. Thromb Haemost 1999; 82 (05) 1456-1461
• 16 Blombäck M, Konkle BA, Manco-Johnson MJ, Bremme K, Hellgren M, Kaaja R. ISTH SSC Subcommittee on Women's Health Issues. Preanalytical conditions that affect coagulation testing, including hormonal status and therapy. J Thromb Haemost 2007; 5 (04) 855-858
• 17 Weitz JI, Strony J, Ageno W. et al; AXIOMATIC-TKR Investigators. Milvexian for the prevention of venous thromboembolism. N Engl J Med 2021; 385 (23) 2161-2172
• 18 Piccini JP, Caso V, Connolly SJ. et al; PACIFIC-AF Investigators. Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study. Lancet 2022; 399 (10333): 1383-1390
• 19 Shoamanesh A, Mundl H, Smith EE. et al; PACIFIC-Stroke Investigators. Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet 2022; 400 (10357): 997-1007
• 20 Rao SV, Kirsch B, Bhatt DL. et al; PACIFIC AMI Investigators. A multicenter, phase 2, randomized, placebo-controlled, double-blind, parallel-group, dose-finding trial of the oral factor XIa inhibitor asundexian to prevent adverse cardiovascular outcomes after acute myocardial infarction. Circulation 2022; 146 (16) 1196-1206
• 21 Tanboga IH, Topcu S, Aksakal E, Kalkan K, Sevimli S, Acikel M. Determinants of angiographic thrombus burden in patients with ST-segment elevation myocardial infarction. Clin Appl Thromb Hemost 2014; 20 (07) 716-722
• 22 Gibson CM, Cannon CP, Daley WL. et al. TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation 1996; 93 (05) 879-888
• 23 Urban P, Gregson J, Owen R. et al. Assessing the risks of bleeding vs thrombotic events in patients at high bleeding risk after coronary stent implantation: the ARC-high bleeding risk trade-off model. JAMA Cardiol 2021; 6 (04) 410-419
• 24 Zhu H, Xu X, Ahn C. Sample size considerations for paired experimental design with incomplete observations of continuous outcomes. Stat Methods Med Res 2019; 28 (02) 589-598
• 25 Zhou X-H, Obuchowski NA, McClish DK. Statistical Methods in Diagnostic Medicine. Wiley Series in Probability and Statistics. John Wiley & Sons, Inc.; 2011
• 26 Rosnow RL, Rosenthal R, Rubin DB. Contrasts and correlations in effect-size estimation. Psychol Sci 2000; 11 (06) 446-453
• 27 Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol 1996; 49 (12) 1373-1379
• 28 Pfeffer MA, Kohs TCL, Vu HH. et al. Factor XI inhibition for the prevention of catheter-associated thrombosis in patients with cancer undergoing central line placement: a phase 2 clinical trial. Arterioscler Thromb Vasc Biol 2024; 44 (01) 290-299