Keywords
Intensive medicine
Venous thromboembolism
Risk prediction
Submitted : 2025-12-10
Accepted : 2025-12-25
Published : 2026-01-09
Abstract
Objective: Whether patients with venous thromboembolism (VTE) receive targeted treatment or not, their mortality rates remain relatively high. Common risk factors for VTE include tumors, trauma, obesity, infection, and gene mutations related to the coagulation/anticoagulation system. However, research on the relationship between non-coagulation/anticoagulation system gene mutations and VTE is currently insufficient. Methods: This study retrospectively collected clinical data from 123 patients in the Department of Critical Care Medicine at Nanjing Jiangning Hospital from June 1, 2023, to December 31, 2024. Through univariate and multivariate analyses, risk factors for VTE in critically ill patients were identified, and a risk prediction model was constructed. Results: The proportion of patients carrying the ALDH2*2 genotype was higher in the VTE group than in those with the ALDH2*1 genotype (21.3% vs 7.9%, P = 0.032). Patients carrying the ALDH2*2 genotype had a 6.553-fold increased risk of developing VTE compared to those with the ALDH2*1 genotype. Patients with a history of diabetes had an 11.491-fold increased risk of VTE compared to those without diabetes, while patients with a history of smoking had a 39.302-fold increased risk compared to non-smokers. For each additional year of age, the risk of VTE increased by 12.5%. For each one-unit increase in left ventricular shortening fraction, the risk of VTE decreased by 37.4%. Conclusion: Mutation of the mitochondrial metabolic enzyme ALDH2 is a risk factor for VTE in critically ill patients and may represent a novel pathway for VTE prevention in this population.
References
Khan F, Tritschler T, Kahn S, et al., 2021, Venous Thromboembolism. Lancet, 398(10294): 64–77.
Sanson B, Simioni P, Tormene D, et al., 1999, Incidence of Venous Thromboembolism in Asymptomatic Carriers of Antithrombin, Protein C, or Protein S Deficiency: A Prospective Cohort Study. Blood, 94(11): 3702–3706.
Heit J, Sobell J, Li H, et al., 2005, Incidence of Venous Thromboembolism among Factor V Leiden Carriers: A Community-Based Cohort Study. Journal of Thrombosis and Haemostasis, 3(2): 305–311.
Folsom A, Cushman M, Tsai M, et al., 2002, Prospective Study of the G20210A Polymorphism in the Prothrombin Gene, Plasma Prothrombin Concentration, and Incidence of Venous Thromboembolism. American Journal of Hematology, 71(4): 285–290.
Tang W, Teichert M, Chasman D, et al., A Genome-Wide Association Study for Venous Thromboembolism: The Extended Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Genetic Epidemiology, 37(5): 512–521.
Lindstrom S, Wang L, Smith E, et al., 2019, Genomic and Transcriptomic Association Studies Identify 16 Novel Susceptibility Loci for Venous Thromboembolism. Blood, 134(19): 1645–1657.
Tang L, Lu X, Yu J, et al., 2012, The PROC c.574_576del Polymorphism: A Prevalent Genetic Risk Factor for Venous Thrombosis in the Chinese Population. Journal of Thrombosis and Haemostasis, 10(10): 2019–2026.
Tang L, Wang H, Lu X, et al., 2013, Common Genetic Risk Factors for Venous Thrombosis in the Chinese Population. American Journal of Human Genetics, 92(2): 177–187.
Zhang R, Wang J, Xue M, et al., 2017, ALDH2 - Genetic Polymorphism and Regulation of Enzymatic Activity: Their Epidemiological and Clinical Implications. Current Drug Targets, 18(15): 1810–1816.
Pan G, Roy B, Palaniyandi S, 2021, Diabetic Aldehyde Dehydrogenase 2 Mutant (ALDH2*2) Mice Exhibit Increased Susceptibility to Cardiac Ischemic-Reperfusion Injury Due to 4-Hydroxy-2-Nonenal-Induced Damage to Coronary Endothelial Cells. Journal of the American Heart Association, 10(18): e021140.
Tsai H, Hsu Y, Lu C, et al., 2021, Pharmacological Activation of Aldehyde Dehydrogenase 2 Confers Protection Against Heatstroke-Induced Acute Lung Injury by Modulating Oxidative Stress and Endothelial Dysfunction. Frontiers in Immunology, 2021(12): 740562.
Engelmann B, Massberg S, 2013. Thrombosis as an Intravascular Effector of Innate Immunity. Nature Reviews Immunology, 13(1): 34–45.
Pan C, Xing J, Zhang C, et al., 2016, Aldehyde Dehydrogenase 2 Inhibits Inflammatory Response and Regulates Atherosclerotic Plaque. Oncotarget, 7(24): 35562–35576.
Liu H, Hu Q, Ren K, et al., 2023, ALDH2 Mitigates LPS-Induced Cardiac Dysfunction, Inflammation, and Apoptosis Through the cGAS/STING Pathway. Molecular Medicine, 29(1): 171.
Heit A, Leibson C, Ashrani A, et al., 2009, Is Diabetes Mellitus an Independent Risk Factor for Venous Thromboembolism? A Population-Based Case-Control Study. Arteriosclerosis, Thrombosis, and Vascular Biology, 29(9): 1399–1405.
Gregson J, Kaptoge S, Bolson T, et al., 2019, Cardiovascular Risk Factors Associated With Venous Thromboembolism. JAMA Cardiology, 4(2): 163–173.
Silverstein M, Heit J, Mohr D, et al., 1998, Trends in the Incidence of Deep Vein Thrombosis and Pulmonary Embolism: A 25-Year Population-Based Study. Archives of Internal Medicine, 158(6): 585–593.
Bochenek M, Schutz E, Schafer K, 2016, Endothelial Cell Senescence and Thrombosis: Ageing Clots. Thrombosis Research, 2016(147): 36–45.
Pastori D, Cormaci V, Marucci S, et al., 2023, A Comprehensive Review of Risk Factors for Venous Thromboembolism: From Epidemiology to Pathophysiology. International Journal of Molecular Sciences, 24(4): 3169.