Hypomagnesemia is a Risk Factor for Venous Thromboembolism (VTE) in Acutely Ill, Hospitalized Elderly Patients. A Retrospective Cohort Analysis of 6,428 Patients.

Hypomagnesemia is a Risk Factor for Venous Thromboembolism (VTE) in Acutely Ill, Hospitalized Elderly Patients. 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A Retrospective Cohort Analysis of 6,428 Patients. Omer Sela, Guy Dumanis, Eddie Klaiman, Dor Warschavsky, Sapir Haim, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4626225/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Nov, 2025 Read the published version in BMC Geriatrics → Version 1 posted 10 You are reading this latest preprint version Abstract Background. Hypomagnesemia, known to be associated with physiologic stress and states of inflammation, is also known to be common in acutely ill, hospitalized patients. The potential association between hypomagnesemia and increased risk for VTE (venous thromboembolism) is not well established. Methods. This was a retrospective analysis of acutely ill, hospitalized elderly patients in a tertiary medical center. Results. A cohort of 6,428 elderly hospitalized patients (57.8% males, median age 77 years (IQR 71 - 84)) included 3,007 (46.8%) with hypomagnesemia (Mg < 1.8 mg/dL). Amongst the hypomagnesemia group of patients, the median age was 76 (IQR 70 – 82). There was no significant difference in the rates of background thrombophilia between both study groups (0.4% vs. 0.3%; p = 0.47). Background malignancy more common in the hypomagnesemia group (6.7% vs. 4.3%; p < 0.001). Usage of proton pump inhibitors was more prevalent in the hypomagnesemia group (49.9% vs. 43%; p < 0.001). The occurrence of VTE by 30 days of admission was significantly higher amongst patients with hypomagnesemia (3% vs. 2.1%, OR = 1.45 CI95% 1.06 – 1.99; p = 0.02). In a multivariate analysis, controlling for age, gender, background malignancy, chronic kidney disease and thrombophilia, hypomagnesemia was still, independently associated with increased occurrence of 30-days VTE [OR = 1.42, CI95% 1.04 – 1.96; P = 0.029]. Conclusions. Amongst hospitalized, acutely ill, elderly patients, hypomagnesemia is independently associated with an increased risk of VTE. Hypomagnesemia Venous Thromboembolism Coagulopathy Elderly Hospitalized patients Risk factor Figures Figure 1 Background Role of magnesium in events of physiologic stress . Being the most common bivalent cation in the intra-cellular domain, Magnesium has dominant roles in many, essential, physiologic processes ( 1 ). Previous publications focused on the bilateral relationship between low magnesium blood levels and physiologic stress ( 2 ). Low magnesium levels were shown to be a pro-inflammatory agent: acting on both innate and acquired immunity cells, hypomagnesemia ignite the oxidative surge on behalf of phagocytic cells and increase the cytokines production by the cellular elements of the adaptive immunity ( 3 , 4 ). In their extensive and thorough review, Veronse et al. found out that explicit beneficial effects of magnesium supplementation (versus placebo or no intervention) were found in the following scenarios: hospitalization prevention of pregnant women and reduction of the risk for Migraine attacks ( 5 ). Deranged magnesium metabolism in septic patients . Hypomagnesemia is known to be both common in patients hospitalized in Intensive Care Units (ICUs) and to have a negative effect on significant clinical outcomes, including survival, respiratory insufficiency and increased length of ICU stay ( 6 ). Wang et al. suggested a mechanism which may render patients with hypomagnesemia to be in a greater risk for sepsis, septic shock and death during their ICU stay. They describe a pathophysiologic mechanism that associates hypomagnesemia with lower monocyte counts and increased tendency for septic shock evolution in terms of gram-negative bacteremia ( 7 ). Alongside its direct effects on immunity and inflammation, magnesium deficiency also accelerates coagulation in favor over fibrinolysis. Tonai et al. found out, in their observational study, that septic patients with low blood magnesium levels were at increased risk of events of disseminated intravascular coagulation (DIC) ( 8 ). Hypomagnesemia also has deleterious effects on the structure and physiology of vascular walls. A previous study showed evidence that magnesium regulates elastin and collagen turnover in the vessel walls. This contributes to the protective effect against atherosclerosis by maintaining the elasticity of the endothelium and decreasing calcium deposition in the elastic fibers ( 9 ). Maier et al. found a correlation between low magnesium and increased risk of cardiovascular diseases, mediated by the fact that hypomagnesemia might reversibly inhibit endothelial cell proliferation, therefore increasing the risk of thrombosis and atherosclerosis ( 10 ). Locatelli et al. suggested that low magnesium can elevate lipid accumulation intracellularly and furthermore disrupt endothelial homeostasis and exacerbate atherosclerosis ( 11 ). Beneficial effects of magnesium administration in critically ill patients . In their prospective observation, Patil and Aslam showed that hypomagnesemia is indeed associated with worse clinical outcomes (Sequential Organ Failure Assessment score (SOFA), ICU length of hospitalization and mortality) in a statistically significant manner. However, they did not present the relative contribution of hypomagnesemia in a multivariate model ( 12 ). In their retrospective analysis of over 6,000 ICU patients, Gu et al. showed that magnesium administration was beneficial, in terms of 28-days mortality rate reduction, even without consideration of the baseline magnesium blood levels of patients. The beneficial effects of magnesium supplementation increased when patients with hypomagnesemia were compared to patients with normal magnesium blood levels ( 13 ). Aim of the current study . In the current study we aimed to assess the potential association between hypomagnesemia and the relative risk for VTE amongst hospitalized, elderly patients. Methods Study cohort . After approval of an Institutional Review Board (IRB) at the Chaim Sheba Medical Center (approval # SMC-1104-24-D) the electronic medical records (EMRs) of patients were addressed. The CONSORT flow of patients in this study is presented in Fig. 1 . Statistical analysis . Continuous variables were tested for distribution by q-q plots. Normally distributed variables were described by mean and standard deviations while those with abnormal distribution were described as median and Inter-Quartile Range (IQR). Categorial variables were described as numbers and percentages. Correlations between patients’ characteristics and clinical outcomes were analyzed: categorial variables’ correlations were assessed using chi-square testing. Continuous, normally distributed variables were analyzed using students’ T-tests while those with anormal distribution were analyzed with non-parametric tests (Willcoxon-Signed ranked test). The association between hypomagnesemia and the primary clinical outcome (VTE) was assessed using Logistic Regression and Odds Ratio (OR) calculation. P value < 0.05 was considered as statistically significant. All statistical analyses were executed by R-Studio software. Results Patients’ characteristics according to blood magnesium levels . Table 1 present our patients’ characteristics according to their magnesium blood levels: the whole study cohort included 6,428 patients of whom 3,007 (46.8%) had magnesium levels below 1.8 mg/dL while the other 3,421 (53.2%) had normal magnesium levels. Amongst patients with hypomagnesemia, males were less prevalent (1,645 (54,7%) vs. 2,073 (60.6%); p < 0.001). The median age was lower amongst patients with hypomagnesemia (76 [IQR 70–82] vs. 78 [IQR 72–84]; p < 0.001). Thrombophilia was more prevalent amongst the hypomagnesemia group, although without statistical significance 13 (0.4%) vs. 10 (0.3%); (p = 0.466). Background Malignancy was evident in 348 (5.4%) patients, of whom 202 (6.7%) were with hypomagnesemia vs. 146 (4.3%) with normal magnesium levels (p < 0.001). the prevalence of chronic kidney diseases was not significantly different between our study cohort groups: 107 (3.6%) in the hypomagnesemia group vs. 139 (4.1%) in patients with normal magnesium levels. With relation to chronic medications that are potentially associated with hypomagnesemia: Proton pump inhibitors were used by 2,970 (46.2%) patients, of whom 1,499 (49.9%) had hypomagnesemia and 1,471 (43%) patients with normal magnesium levels (p < 0.001). Diuretics were used by 2,390 (37.2%) patients in the whole study cohort, of whom 1,016 (33.8%) had low magnesium levels while 1,374 (40.25%) had normal magnesium levels (p < 0.001). H 2 blockers were used by 207 (6.9%) patients with hypomagnesemia vs. 269 (7.9%) in patients with normal magnesium levels (p = 0.148). By 30 days after hospital admission, VTE occurred in 91 (3%) patients with hypomagnesemia vs. 72 (2.1%) of patients with normal range serum magnesium (p = 0.023). The median length of hospitalization was 6 days (IQR 3–14) in patients with hypomagnesemia vs. 4 days (IQR 2–7) for patients with normal magnesium levels (p < 0.001). In-hospital mortality occurred in 363 (12.1%) patients with hypomagnesemia vs. 472 (13.8%) patients with normal magnesium levels (p = 0.044). Mortality by 30 days after admission was lower amongst patients with hypomagnesemia 444 (14.8%) vs. 610 (16.4%) in patients with normal magnesium (p = 0.001). Table 01 Whole study cohort patients’ characteristics Patients' Characteristics Overall N = 6,428 Mg < 1.8 mg/dL N = 3,007 (46.8%) Mg ≥ 1.8 mg/dL N = 3,421 (53.2%) P - value Patients' Demographics Gender; Male, N (%) 3,718 (57.8) 1,645 (54.7) 2,073 (60.6) < 0.001 Age (median [IQR]) 77 [71, 84] 76 [70, 82] 78 [72, 84] < 0.001 Background Thrombophilia; N (%) 23 (0.4) 13 (0.4) 10 (0.3) 0.466 Malignancy; N (%) 348 (5.4) 202 (6.7) 146 (4.3) < 0.001 Chronic Kidney Disease; N (%) 246 (3.8) 107 (3.6) 139 (4.1) 0.323 Chronic Medications Proton pump inhibitors; N (%) 2,970 (46.2) 1,499 (49.9) 1,471 (43.0) < 0.001 H2 blockers; N (%) 476 (7.4) 207 (6.9) 269 (7.9) 0.148 Diuretics; N (%) 2,390 (37.2) 1,016 (33.8) 1,374 (40.2) < 0.001 Clinical Outcomes VTE by day 30 from admission; N (%) 163 (2.5) 91 ( 3 ) 72 (2.1) 0.023 Length of hospital stay; days (median [IQR]) 4 [2, 10] 6 [3, 14] 4 [2, 7] < 0.001 In-hospital mortality; N (%) 835 ( 13 ) 363 (12.1) 472 (13.8) 0.044 30-day mortality; N (%) 1,054 (16.4) 444 (14.8) 610 (17.8) 0.001 Univariate and Multivariate analysis In a univariate analysis (Table 2 ), in-hospital hypomagnesemia was associated with increased risk for in-hospital VTE by 45% (OR = 1.45, 95% CI [1.06, 1.99]; p = 0.02). In a multivariate analysis, controlling for age, gender, background malignancy, chronic kidney disease and thrombophilia, hypomagnesemia was still, independently associated with increased occurrence of 30-days VTE [OR = 1.42, CI95% 1.04–1.96; P = 0.029]. Table 2 Logistic regression analysis for 30-days VTE occurrence. Variable OR [95% CI] P-value Univariate model Hypomagnesemia 1.45 [1.06, 1.99] 0.02 Multivariate model Age (per year) 1.01 [0.99, 1.03] 0.358 Male gender 0.65 [0.47, 0.89] 0.007 Hypomagnesemia 1.42 [1.04, 1.96] 0.029 Chronic kidney disease 1.67 [0.81, 3.07] 0.128 Malignancy 1.7 [0.94, 2.84] 0.057 Thrombophilia 3.56 [0.57, 12.42] 0.088 Discussion Previously recognized VTE risk factors . Venous-thromboembolism (VTE), being a significant contributor for in-hospital morbidity and mortality, deserve a significant portion of literature relating to the risk factors for this phenomenon: in their systematic review and meta-analysis of 17 studies, Darzi et al. identified the following risk factors for VTE in hospitalized patients: older age; elevated inflammation markers, elevated blood components suggestive of active fibrinolysis, tachycardia, leg edema and decreased mobility ( 14 ). Gao et al. in their later meta-analysis of 42 studies did not add significantly to the already known VTE risk factors in patients hospitalized in intensive care units ( 15 ). Several authors concentrated on risk factors in unique patients’ populations, e.g. cancer patients ( 16 ), post major surgery ( 17 ), and metabolic derangements ( 18 ). A thorough literature search did not recover previous publications identifying hypomagnesemia as a risk factor for VTE. Hypomagnesemia amongst critically ill patients . Hypomagnesemia is long known to be associated with worse prognosis in critically ill patients. It is considered the more prevalent type of dysmagnesemia, defined as hypo- and hypermagnesemia together ( 19 ). In their study of 65,974 patients, Cheungpasitporn and co. defined dysmagnesemia as a risk factor for in-patient deterioration with hypomagnesemia (below 1.7 mg/dL) serving as a risk factor for increased mortality ( 20 ). In our study cohort, hypermagnesemia rather than hypomagnesemia, was associated with longer in-hospital stay and mortality. The discrepancies between our findings and Cheungpasitporn could be stemming from the different age groups of patients. In both studies, malignancy was more prevalent in patients with hypomagnesemia. In both studies, elevated magnesium levels were associated with increased risk of mortality. Upala et al. in their systematic review and meta-analysis of 6 studies showed that hypomagnesemia (in the range of serum magnesium lower than 1.5 to 1.8 mg/dL) was associated with 90% increased risk of in-hospital mortality, 65% increased risk for need of mechanical ventilation and with a prolonged ICU length of stay ( 21 ). They did not assess the potential association between hypomagnesemia and VTE. In the introduction of this manuscript, the potential association between hypomagnesemia and increased risk of pathologic coagulation was described. Nevertheless, a direct association between hypomagnesemia and increased incidence of VTE was not previously published. In their publication ( 22 ), Wang et al. described a combination of hypomagnesemia and increased incidence of VTE but without a causative relation. They described both, as consequences of platinum-based chemotherapy. The authors of the current manuscript would like to emphasize the importance of our findings: the combination of an easily correctable phenomenon (hypomagnesemia) and a life-threatening occurrence amongst critically ill, elderly patients (VTE) should be kept in mind of all practicing physicians, taking care of these patients. Conclusions Hypomagnesemia amongst critically ill, elderly patients is an independent risk factor for venous thromboembolism. In-hospital practicing physicians should be aware of this association. The question of the potential benefit of hypomagnesemia correction as means for lowering patients’ risk for VTE remains open. Limitations This was a retrospective analysis of patients from a single medical center. Therefore, our findings should be carefully re-investigated in more heterogenous patients’ populations. We describe an association, but causative relation cannot be inferred. Declarations Ethics approval and consent to participate : The electronic medical records of patients were addressed only after approval of an Institutional Review Board (IRB) at the Chaim Sheba Medical Center (approval # SMC-1104-24-D). The IRB waived the need for informed consent due to the retrospective, non-interventional nature of this study. Consent for publication Not applicable, as this was a retrospective study. Availability of data and material The data on which this study rely will be available as anonymized data upon request from the principal investigator / corresponding author of this manuscript. Competing interests All authors declare they have no competing interests regarding this study and the publication of this manuscript. Funding Non applicable. This study did not receive any external funding to be reported. Authors' contributions All authors contributed significantly to this study and manuscript: conception, design, data mining, data analysis, draft writing and writing and approval of the final manuscript version submitted. Acknowledgements Non applicable. References Tangvoraphonkchai K, Davenport A. Magnesium and Cardiovascular Disease. Adv Chronic Kidney Dis [Internet]. 2018 May 1 [cited 2024 Feb 8];25(3):251–60. https://pubmed.ncbi.nlm.nih.gov/29793664/ . Pickering G, Mazur A, Trousselard M, Bienkowski P, Yaltsewa N, Amessou M et al. Magnesium Status and Stress: The Vicious Circle Concept Revisited. Nutrients [Internet]. 2020 Dec 1 [cited 2024 Jan 25];12(12):1–21. Available from: /pmc/articles/PMC7761127/. Maier JA, Castiglioni S, Locatelli L, Zocchi M, Mazur A. Magnesium and inflammation: Advances and perspectives. Semin Cell Dev Biol [Internet]. 2021 Jul 1 [cited 2024 Feb 8];115:37–44. https://pubmed.ncbi.nlm.nih.gov/33221129/ . Barbagallo M, Veronese N, Dominguez LJ. Magnesium in Aging, Health and Diseases. Nutrients [Internet]. 2021 Feb 1 [cited 2024 Feb 22];13(2):1–20. Available from: /pmc/articles/PMC7912123/. Veronese N, Demurtas J, Pesolillo G, Celotto S, Barnini T, Calusi G et al. Magnesium and health outcomes: an umbrella review of systematic reviews and meta-analyses of observational and intervention studies. Eur J Nutr [Internet]. 2020 Feb 1 [cited 2024 Feb 8];59(1):263–72. https://pubmed.ncbi.nlm.nih.gov/30684032/ . Velissaris D, Karamouzos V, Pierrakos C, Aretha D, Karanikolas M. Hypomagnesemia in Critically Ill Sepsis Patients. J Clin Med Res [Internet]. 2015 [cited 2024 Feb 8];7(12):911–8. https://pubmed.ncbi.nlm.nih.gov/26566403/ . Wang D, Zheng J, Hu Q, Zhao C, Chen Q, Shi P et al. Magnesium protects against sepsis by blocking gasdermin D N-terminal-induced pyroptosis. Cell Death Differ [Internet]. 2020 Feb 1 [cited 2024 Feb 8];27(2):466. /pmc/articles/PMC7206066/ . Tonai K, Katayama S, Koyama K, Sata N, Tomioka Y, Imahase H et al. Association between hypomagnesemia and coagulopathy in sepsis: a retrospective observational study. BMC Anesthesiol [Internet]. 2022 Dec 1 [cited 2024 Feb 8];22(1). https://pubmed.ncbi.nlm.nih.gov/36424547/ . Kostov K, Halacheva L. Role of Magnesium Deficiency in Promoting Atherosclerosis, Endothelial Dysfunction, and Arterial Stiffening as Risk Factors for Hypertension. Int J Mol Sci [Internet]. 2018 Jun 11 [cited 2024 Apr 17];19(6). https://pubmed.ncbi.nlm.nih.gov/29891771/ . Maier JAM, Malpuech-Brugère C, Zimowska W, Rayssiguier Y, Mazur A. Low magnesium promotes endothelial cell dysfunction: implications for atherosclerosis, inflammation and thrombosis. Biochim Biophys Acta [Internet]. 2004 May 1 [cited 2024 Apr 17];1689(1):13–21. https://europepmc.org/article/MED/15158909 . Locatelli L, Fedele G, Castiglioni S, Maier JA. Magnesium Deficiency Induces Lipid Accumulation in Vascular Endothelial Cells via Oxidative Stress—The Potential Contribution of EDF-1 and PPARγ. International Journal of Molecular Sciences. 2021, Vol 22, Page 1050 [Internet]. 2021 Jan 21 [cited 2024 Apr 17];22(3):1050. https://www.mdpi.com/1422-0067/22/3/1050/htm . Patil PSG, Aslam SS. Study of Serum Magnesium Levels in Patients Admitted with Sepsis in Intensive Care Unit. Kathmandu Univ Med J (KUMJ) [Internet]. 2023 Jan 1 [cited 2024 Jan 25];21(81):23–7. https://pubmed.ncbi.nlm.nih.gov/37800421/ . Gu WJ, Duan XJ, Liu XZ, Cen Y, Tao LY, Lyu J et al. Association of magnesium sulfate use with mortality in critically ill patients with sepsis: a retrospective propensity score-matched cohort study. Br J Anaesth [Internet]. 2023 Nov 1 [cited 2024 Jan 25];131(5):861–70. https://pubmed.ncbi.nlm.nih.gov/37684164/ . Darzi AJ, Karam SG, Charide R, Etxeandia-Ikobaltzeta I, Cushman M, Gould MK et al. Prognostic factors for VTE and bleeding in hospitalized medical patients: a systematic review and meta-analysis. Blood [Internet]. 2020 May 4 [cited 2024 Jun 2];135(20):1788–810. https://pubmed.ncbi.nlm.nih.gov/32092132/ . Gao X, Zeng L, Wang H, Zeng S, Tian J, Chen L et al. Prevalence of Venous Thromboembolism in Intensive Care Units: A Meta-Analysis. J Clin Med [Internet]. 2022 Nov 1 [cited 2024 Jun 2];11(22). https://pubmed.ncbi.nlm.nih.gov/36431168/ . Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer [Internet]. 2007 Nov 15 [cited 2024 Jun 2];110(10):2339–46. https://pubmed.ncbi.nlm.nih.gov/17918266/ . Heijkoop B, Parker N, Kiroff G, Spernat D. Effectiveness and safety of inpatient versus extended venous thromboembolism (VTE) prophylaxis with heparin following major pelvic surgery for malignancy: protocol for a systematic review. Syst Rev [Internet]. 2019 Oct 30 [cited 2024 Jun 2];8(1). https://pubmed.ncbi.nlm.nih.gov/31666130/ . van Haalen FM, Kaya M, Pelsma ICM, Dekkers OM, Biermasz NR, Cannegieter SC et al. Current clinical practice for thromboprophylaxis management in patients with Cushing’s syndrome across reference centers of the European Reference Network on Rare Endocrine Conditions (Endo-ERN). Orphanet J Rare Dis [Internet]. 2022 Dec 1 [cited 2024 Jun 2];17(1). https://pubmed.ncbi.nlm.nih.gov/35505430/ . Al Shukri Z, Al-Maqbali JS, Al Alawi AM, Al Riyami N, Al Riyami S, Al Alawi H et al. Incidence of Dysmagnesemia among Medically Hospitalized Patients and Associated Clinical Characteristics: A Prospective Cohort Study. Int J Endocrinol [Internet]. 2023 [cited 2024 Jun 23];2023. https://pubmed.ncbi.nlm.nih.gov/37829115/ . Cheungpasitporn W, Thongprayoon C, Qian Q. Dysmagnesemia in Hospitalized Patients: Prevalence and Prognostic Importance. Mayo Clin Proc [Internet]. 2015 Aug 1 [cited 2024 Jun 2];90(8):1001–10. https://pubmed.ncbi.nlm.nih.gov/26250725/ . Upala S, Jaruvongvanich V, Wijarnpreecha K, Sanguankeo A. Hypomagnesemia and mortality in patients admitted to intensive care unit: a systematic review and meta-analysis. QJM [Internet]. 2016 Jul 1 [cited 2024 Jun 2];109(7):453–9. https://pubmed.ncbi.nlm.nih.gov/27016536/ . Wang L, Liao C, Li M, Zhang S, Yi F, Wei Y et al. Necitumumab plus platinum-based chemotherapy versus chemotherapy alone as first-line treatment for stage IV non-small cell lung cancer: a meta-analysis based on randomized controlled trials. Ann Palliat Med [Internet]. 2021 [cited 2024 Jun 23];10(2):1154166–1151166. https://apm.amegroups.org/article/view/51805/html . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Nov, 2025 Read the published version in BMC Geriatrics → Version 1 posted Editorial decision: Revision requested 31 Jul, 2025 Reviews received at journal 26 Jul, 2025 Reviewers agreed at journal 16 Jul, 2025 Reviews received at journal 09 Sep, 2024 Reviewers agreed at journal 01 Sep, 2024 Reviewers invited by journal 23 Aug, 2024 Editor invited by journal 02 Jul, 2024 Editor assigned by journal 29 Jun, 2024 Submission checks completed at journal 29 Jun, 2024 First submitted to journal 23 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Center","correspondingAuthor":true,"prefix":"","firstName":"Gad","middleName":"","lastName":"Segal","suffix":""},{"id":325256347,"identity":"0b5ea203-4a08-4553-b99e-bea778692c89","order_by":9,"name":"Adva Vaisman","email":"","orcid":"","institution":"Chaim Sheba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Adva","middleName":"","lastName":"Vaisman","suffix":""}],"badges":[],"createdAt":"2024-06-23 18:09:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4626225/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4626225/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12877-025-06644-8","type":"published","date":"2025-11-18T15:57:03+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60811415,"identity":"6731dc9a-47f9-4409-b5a8-ec0e33a5b8a1","added_by":"auto","created_at":"2024-07-22 10:55:14","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":145323,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT flow of patients.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4626225/v1/3aecc1d164b6e207e2e08408.jpeg"},{"id":96649993,"identity":"8f4d7d02-0ca0-432e-8194-cf9bd3023476","added_by":"auto","created_at":"2025-11-24 16:04:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":716689,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4626225/v1/149fa280-606e-4979-a7e7-d26260bb3d3d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eHypomagnesemia is a Risk Factor for Venous Thromboembolism (VTE) in Acutely Ill, Hospitalized Elderly Patients. \u003c/strong\u003eA Retrospective Cohort Analysis of 6,428 Patients.\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eRole of magnesium in events of physiologic stress\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eBeing the most common bivalent cation in the intra-cellular domain, Magnesium has dominant roles in many, essential, physiologic processes (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Previous publications focused on the bilateral relationship between low magnesium blood levels and physiologic stress (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Low magnesium levels were shown to be a pro-inflammatory agent: acting on both innate and acquired immunity cells, hypomagnesemia ignite the oxidative surge on behalf of phagocytic cells and increase the cytokines production by the cellular elements of the adaptive immunity (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). In their extensive and thorough review, Veronse et al. found out that explicit beneficial effects of magnesium supplementation (versus placebo or no intervention) were found in the following scenarios: hospitalization prevention of pregnant women and reduction of the risk for Migraine attacks (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eDeranged magnesium metabolism in septic patients\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eHypomagnesemia is known to be both common in patients hospitalized in Intensive Care Units (ICUs) and to have a negative effect on significant clinical outcomes, including survival, respiratory insufficiency and increased length of ICU stay (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Wang et al. suggested a mechanism which may render patients with hypomagnesemia to be in a greater risk for sepsis, septic shock and death during their ICU stay. They describe a pathophysiologic mechanism that associates hypomagnesemia with lower monocyte counts and increased tendency for septic shock evolution in terms of gram-negative bacteremia (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Alongside its direct effects on immunity and inflammation, magnesium deficiency also accelerates coagulation in favor over fibrinolysis. Tonai et al. found out, in their observational study, that septic patients with low blood magnesium levels were at increased risk of events of disseminated intravascular coagulation (DIC) (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHypomagnesemia also has deleterious effects on the structure and physiology of vascular walls. A previous study showed evidence that magnesium regulates elastin and collagen turnover in the vessel walls. This contributes to the protective effect against atherosclerosis by maintaining the elasticity of the endothelium and decreasing calcium deposition in the elastic fibers (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Maier et al. found a correlation between low magnesium and increased risk of cardiovascular diseases, mediated by the fact that hypomagnesemia might reversibly inhibit endothelial cell proliferation, therefore increasing the risk of thrombosis and atherosclerosis (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Locatelli et al. suggested that low magnesium can elevate lipid accumulation intracellularly and furthermore disrupt endothelial homeostasis and exacerbate atherosclerosis (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eBeneficial effects of magnesium administration in critically ill patients\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eIn their prospective observation, Patil and Aslam showed that hypomagnesemia is indeed associated with worse clinical outcomes (Sequential Organ Failure Assessment score (SOFA), ICU length of hospitalization and mortality) in a statistically significant manner. However, they did not present the relative contribution of hypomagnesemia in a multivariate model (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). In their retrospective analysis of over 6,000 ICU patients, Gu et al. showed that magnesium administration was beneficial, in terms of 28-days mortality rate reduction, even without consideration of the baseline magnesium blood levels of patients. The beneficial effects of magnesium supplementation increased when patients with hypomagnesemia were compared to patients with normal magnesium blood levels (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAim of the current study\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eIn the current study we aimed to assess the potential association between hypomagnesemia and the relative risk for VTE amongst hospitalized, elderly patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eStudy cohort\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eAfter approval of an Institutional Review Board (IRB) at the Chaim Sheba Medical Center (approval # SMC-1104-24-D) the electronic medical records (EMRs) of patients were addressed. The CONSORT flow of patients in this study is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eStatistical analysis\u003c/span\u003e.\u003c/h2\u003e \u003cp\u003eContinuous variables were tested for distribution by q-q plots. Normally distributed variables were described by mean and standard deviations while those with abnormal distribution were described as median and Inter-Quartile Range (IQR). Categorial variables were described as numbers and percentages. Correlations between patients\u0026rsquo; characteristics and clinical outcomes were analyzed: categorial variables\u0026rsquo; correlations were assessed using chi-square testing. Continuous, normally distributed variables were analyzed using students\u0026rsquo; T-tests while those with anormal distribution were analyzed with non-parametric tests (Willcoxon-Signed ranked test). The association between hypomagnesemia and the primary clinical outcome (VTE) was assessed using Logistic Regression and Odds Ratio (OR) calculation. P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered as statistically significant. All statistical analyses were executed by R-Studio software.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePatients\u0026rsquo; characteristics according to blood magnesium levels\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e present our patients\u0026rsquo; characteristics according to their magnesium blood levels: the whole study cohort included 6,428 patients of whom 3,007 (46.8%) had magnesium levels below 1.8 mg/dL while the other 3,421 (53.2%) had normal magnesium levels. Amongst patients with hypomagnesemia, males were less prevalent (1,645 (54,7%) vs. 2,073 (60.6%); p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The median age was lower amongst patients with hypomagnesemia (76 [IQR 70\u0026ndash;82] vs. 78 [IQR 72\u0026ndash;84]; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Thrombophilia was more prevalent amongst the hypomagnesemia group, although without statistical significance 13 (0.4%) vs. 10 (0.3%); (p\u0026thinsp;=\u0026thinsp;0.466). Background Malignancy was evident in 348 (5.4%) patients, of whom 202 (6.7%) were with hypomagnesemia vs. 146 (4.3%) with normal magnesium levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). the prevalence of chronic kidney diseases was not significantly different between our study cohort groups: 107 (3.6%) in the hypomagnesemia group vs. 139 (4.1%) in patients with normal magnesium levels. With relation to chronic medications that are potentially associated with hypomagnesemia: Proton pump inhibitors were used by 2,970 (46.2%) patients, of whom 1,499 (49.9%) had hypomagnesemia and 1,471 (43%) patients with normal magnesium levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Diuretics were used by 2,390 (37.2%) patients in the whole study cohort, of whom 1,016 (33.8%) had low magnesium levels while 1,374 (40.25%) had normal magnesium levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). H\u003csub\u003e2\u003c/sub\u003e blockers were used by 207 (6.9%) patients with hypomagnesemia vs. 269 (7.9%) in patients with normal magnesium levels (p\u0026thinsp;=\u0026thinsp;0.148).\u003c/p\u003e \u003cp\u003eBy 30 days after hospital admission, VTE occurred in 91 (3%) patients with hypomagnesemia vs. 72 (2.1%) of patients with normal range serum magnesium (p\u0026thinsp;=\u0026thinsp;0.023). The median length of hospitalization was 6 days (IQR 3\u0026ndash;14) in patients with hypomagnesemia vs. 4 days (IQR 2\u0026ndash;7) for patients with normal magnesium levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In-hospital mortality occurred in 363 (12.1%) patients with hypomagnesemia vs. 472 (13.8%) patients with normal magnesium levels (p\u0026thinsp;=\u0026thinsp;0.044). Mortality by 30 days after admission was lower amongst patients with hypomagnesemia 444 (14.8%) vs. 610 (16.4%) in patients with normal magnesium (p\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 01\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eWhole study cohort patients\u0026rsquo; characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatients' Characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;6,428\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMg\u0026thinsp;\u0026lt;\u0026thinsp;1.8 mg/dL\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;3,007 (46.8%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMg\u0026thinsp;\u0026ge;\u0026thinsp;1.8 mg/dL\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;3,421 (53.2%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP - value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003ePatients' Demographics\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender; Male, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,718 (57.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,645 (54.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,073 (60.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (median [IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77 [71, 84]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76 [70, 82]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78 [72, 84]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombophilia; N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.466\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignancy; N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e348 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e202 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e146 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic Kidney Disease; N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e246 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e139 (4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.323\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChronic Medications\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProton pump inhibitors; N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,970 (46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,499 (49.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,471 (43.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eH2 blockers; N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e476 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e207 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e269 (7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.148\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiuretics; N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,390 (37.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,016 (33.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,374 (40.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical Outcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVTE by day 30 from admission; N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e163 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of hospital stay; days (median [IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 [2, 10]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 [3, 14]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 [2, 7]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIn-hospital mortality; N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e835 (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e363 (12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e472 (13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30-day mortality; N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,054 (16.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e444 (14.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e610 (17.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eUnivariate and Multivariate analysis\u003c/h2\u003e \u003cp\u003eIn a univariate analysis (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), in-hospital hypomagnesemia was associated with increased risk for in-hospital VTE by 45% (OR\u0026thinsp;=\u0026thinsp;1.45, 95% CI [1.06, 1.99]; p\u0026thinsp;=\u0026thinsp;0.02). In a multivariate analysis, controlling for age, gender, background malignancy, chronic kidney disease and thrombophilia, hypomagnesemia was still, independently associated with increased occurrence of 30-days VTE [OR\u0026thinsp;=\u0026thinsp;1.42, CI95% 1.04\u0026ndash;1.96; P\u0026thinsp;=\u0026thinsp;0.029].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLogistic regression analysis for 30-days VTE occurrence.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR [95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eUnivariate model\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypomagnesemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.45 [1.06, 1.99]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMultivariate model\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (per year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.01 [0.99, 1.03]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.358\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale gender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.65 [0.47, 0.89]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypomagnesemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.42 [1.04, 1.96]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic kidney disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.67 [0.81, 3.07]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.128\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.7 [0.94, 2.84]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.057\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombophilia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.56 [0.57, 12.42]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePreviously recognized VTE risk factors\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eVenous-thromboembolism (VTE), being a significant contributor for in-hospital morbidity and mortality, deserve a significant portion of literature relating to the risk factors for this phenomenon: in their systematic review and meta-analysis of 17 studies, Darzi et al. identified the following risk factors for VTE in hospitalized patients: older age; elevated inflammation markers, elevated blood components suggestive of active fibrinolysis, tachycardia, leg edema and decreased mobility (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Gao et al. in their later meta-analysis of 42 studies did not add significantly to the already known VTE risk factors in patients hospitalized in intensive care units (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Several authors concentrated on risk factors in unique patients\u0026rsquo; populations, e.g. cancer patients (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), post major surgery (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), and metabolic derangements (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). A thorough literature search did not recover previous publications identifying hypomagnesemia as a risk factor for VTE.\u003c/p\u003e \u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eHypomagnesemia amongst critically ill patients\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eHypomagnesemia is long known to be associated with worse prognosis in critically ill patients. It is considered the more prevalent type of dysmagnesemia, defined as hypo- and hypermagnesemia together (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). In their study of 65,974 patients, Cheungpasitporn and co. defined dysmagnesemia as a risk factor for in-patient deterioration with hypomagnesemia (below 1.7 mg/dL) serving as a risk factor for increased mortality (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). In our study cohort, hypermagnesemia rather than hypomagnesemia, was associated with longer in-hospital stay and mortality. The discrepancies between our findings and Cheungpasitporn could be stemming from the different age groups of patients. In both studies, malignancy was more prevalent in patients with hypomagnesemia. In both studies, elevated magnesium levels were associated with increased risk of mortality. Upala et al. in their systematic review and meta-analysis of 6 studies showed that hypomagnesemia (in the range of serum magnesium lower than 1.5 to 1.8 mg/dL) was associated with 90% increased risk of in-hospital mortality, 65% increased risk for need of mechanical ventilation and with a prolonged ICU length of stay (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). They did not assess the potential association between hypomagnesemia and VTE.\u003c/p\u003e \u003cp\u003eIn the introduction of this manuscript, the potential association between hypomagnesemia and increased risk of pathologic coagulation was described. Nevertheless, a direct association between hypomagnesemia and increased incidence of VTE was not previously published. In their publication (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), Wang et al. described a combination of hypomagnesemia and increased incidence of VTE but without a causative relation. They described both, as consequences of platinum-based chemotherapy.\u003c/p\u003e \u003cp\u003eThe authors of the current manuscript would like to emphasize the importance of our findings: the combination of an easily correctable phenomenon (hypomagnesemia) and a life-threatening occurrence amongst critically ill, elderly patients (VTE) should be kept in mind of all practicing physicians, taking care of these patients.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eHypomagnesemia amongst critically ill, elderly patients is an independent risk factor for venous thromboembolism. In-hospital practicing physicians should be aware of this association. The question of the potential benefit of hypomagnesemia correction as means for lowering patients\u0026rsquo; risk for VTE remains open.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThis was a retrospective analysis of patients from a single medical center. Therefore, our findings should be carefully re-investigated in more heterogenous patients\u0026rsquo; populations. We describe an association, but causative relation cannot be inferred.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cu\u003eEthics approval and consent to participate\u003c/u\u003e:\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe electronic medical records of patients were addressed only after approval of an Institutional Review Board (IRB) at the Chaim Sheba Medical Center (approval # SMC-1104-24-D). The IRB waived the need for informed consent due to the retrospective, non-interventional nature of this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConsent for publication\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable, as this was a retrospective study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAvailability of data and material\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe data on which this study rely will be available as anonymized data upon request from the principal investigator / corresponding author of this manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCompeting interests\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare they have no competing interests regarding this study and the publication of this manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eFunding\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNon applicable. This study did not receive any external funding to be reported. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAuthors\u0026apos; contributions\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed significantly to this study and manuscript: conception, design, data mining, data analysis, draft writing and writing and approval of the final manuscript version submitted.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAcknowledgements\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNon applicable.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTangvoraphonkchai K, Davenport A. Magnesium and Cardiovascular Disease. Adv Chronic Kidney Dis [Internet]. 2018 May 1 [cited 2024 Feb 8];25(3):251\u0026ndash;60. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/29793664/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/29793664/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePickering G, Mazur A, Trousselard M, Bienkowski P, Yaltsewa N, Amessou M et al. Magnesium Status and Stress: The Vicious Circle Concept Revisited. Nutrients [Internet]. 2020 Dec 1 [cited 2024 Jan 25];12(12):1\u0026ndash;21. Available from: /pmc/articles/PMC7761127/.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaier JA, Castiglioni S, Locatelli L, Zocchi M, Mazur A. Magnesium and inflammation: Advances and perspectives. Semin Cell Dev Biol [Internet]. 2021 Jul 1 [cited 2024 Feb 8];115:37\u0026ndash;44. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/33221129/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/33221129/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarbagallo M, Veronese N, Dominguez LJ. Magnesium in Aging, Health and Diseases. Nutrients [Internet]. 2021 Feb 1 [cited 2024 Feb 22];13(2):1\u0026ndash;20. Available from: /pmc/articles/PMC7912123/.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVeronese N, Demurtas J, Pesolillo G, Celotto S, Barnini T, Calusi G et al. Magnesium and health outcomes: an umbrella review of systematic reviews and meta-analyses of observational and intervention studies. Eur J Nutr [Internet]. 2020 Feb 1 [cited 2024 Feb 8];59(1):263\u0026ndash;72. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/30684032/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/30684032/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVelissaris D, Karamouzos V, Pierrakos C, Aretha D, Karanikolas M. Hypomagnesemia in Critically Ill Sepsis Patients. J Clin Med Res [Internet]. 2015 [cited 2024 Feb 8];7(12):911\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/26566403/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/26566403/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang D, Zheng J, Hu Q, Zhao C, Chen Q, Shi P et al. Magnesium protects against sepsis by blocking gasdermin D N-terminal-induced pyroptosis. Cell Death Differ [Internet]. 2020 Feb 1 [cited 2024 Feb 8];27(2):466. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e/pmc/articles/PMC7206066/\u003c/span\u003e\u003cspan address=\"http:///pmc/articles/PMC7206066/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTonai K, Katayama S, Koyama K, Sata N, Tomioka Y, Imahase H et al. Association between hypomagnesemia and coagulopathy in sepsis: a retrospective observational study. BMC Anesthesiol [Internet]. 2022 Dec 1 [cited 2024 Feb 8];22(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/36424547/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/36424547/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKostov K, Halacheva L. Role of Magnesium Deficiency in Promoting Atherosclerosis, Endothelial Dysfunction, and Arterial Stiffening as Risk Factors for Hypertension. Int J Mol Sci [Internet]. 2018 Jun 11 [cited 2024 Apr 17];19(6). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/29891771/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/29891771/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaier JAM, Malpuech-Brug\u0026egrave;re C, Zimowska W, Rayssiguier Y, Mazur A. Low magnesium promotes endothelial cell dysfunction: implications for atherosclerosis, inflammation and thrombosis. Biochim Biophys Acta [Internet]. 2004 May 1 [cited 2024 Apr 17];1689(1):13\u0026ndash;21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://europepmc.org/article/MED/15158909\u003c/span\u003e\u003cspan address=\"https://europepmc.org/article/MED/15158909\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLocatelli L, Fedele G, Castiglioni S, Maier JA. Magnesium Deficiency Induces Lipid Accumulation in Vascular Endothelial Cells via Oxidative Stress\u0026mdash;The Potential Contribution of EDF-1 and PPARγ. International Journal of Molecular Sciences. 2021, Vol 22, Page 1050 [Internet]. 2021 Jan 21 [cited 2024 Apr 17];22(3):1050. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.mdpi.com/1422-0067/22/3/1050/htm\u003c/span\u003e\u003cspan address=\"https://www.mdpi.com/1422-0067/22/3/1050/htm\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePatil PSG, Aslam SS. Study of Serum Magnesium Levels in Patients Admitted with Sepsis in Intensive Care Unit. Kathmandu Univ Med J (KUMJ) [Internet]. 2023 Jan 1 [cited 2024 Jan 25];21(81):23\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/37800421/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/37800421/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGu WJ, Duan XJ, Liu XZ, Cen Y, Tao LY, Lyu J et al. Association of magnesium sulfate use with mortality in critically ill patients with sepsis: a retrospective propensity score-matched cohort study. Br J Anaesth [Internet]. 2023 Nov 1 [cited 2024 Jan 25];131(5):861\u0026ndash;70. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/37684164/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/37684164/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDarzi AJ, Karam SG, Charide R, Etxeandia-Ikobaltzeta I, Cushman M, Gould MK et al. Prognostic factors for VTE and bleeding in hospitalized medical patients: a systematic review and meta-analysis. Blood [Internet]. 2020 May 4 [cited 2024 Jun 2];135(20):1788\u0026ndash;810. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/32092132/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/32092132/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGao X, Zeng L, Wang H, Zeng S, Tian J, Chen L et al. Prevalence of Venous Thromboembolism in Intensive Care Units: A Meta-Analysis. J Clin Med [Internet]. 2022 Nov 1 [cited 2024 Jun 2];11(22). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/36431168/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/36431168/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer [Internet]. 2007 Nov 15 [cited 2024 Jun 2];110(10):2339\u0026ndash;46. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/17918266/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/17918266/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeijkoop B, Parker N, Kiroff G, Spernat D. Effectiveness and safety of inpatient versus extended venous thromboembolism (VTE) prophylaxis with heparin following major pelvic surgery for malignancy: protocol for a systematic review. Syst Rev [Internet]. 2019 Oct 30 [cited 2024 Jun 2];8(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/31666130/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/31666130/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Haalen FM, Kaya M, Pelsma ICM, Dekkers OM, Biermasz NR, Cannegieter SC et al. Current clinical practice for thromboprophylaxis management in patients with Cushing\u0026rsquo;s syndrome across reference centers of the European Reference Network on Rare Endocrine Conditions (Endo-ERN). Orphanet J Rare Dis [Internet]. 2022 Dec 1 [cited 2024 Jun 2];17(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/35505430/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/35505430/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAl Shukri Z, Al-Maqbali JS, Al Alawi AM, Al Riyami N, Al Riyami S, Al Alawi H et al. Incidence of Dysmagnesemia among Medically Hospitalized Patients and Associated Clinical Characteristics: A Prospective Cohort Study. Int J Endocrinol [Internet]. 2023 [cited 2024 Jun 23];2023. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/37829115/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/37829115/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheungpasitporn W, Thongprayoon C, Qian Q. Dysmagnesemia in Hospitalized Patients: Prevalence and Prognostic Importance. Mayo Clin Proc [Internet]. 2015 Aug 1 [cited 2024 Jun 2];90(8):1001\u0026ndash;10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/26250725/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/26250725/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUpala S, Jaruvongvanich V, Wijarnpreecha K, Sanguankeo A. Hypomagnesemia and mortality in patients admitted to intensive care unit: a systematic review and meta-analysis. QJM [Internet]. 2016 Jul 1 [cited 2024 Jun 2];109(7):453\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/27016536/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/27016536/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang L, Liao C, Li M, Zhang S, Yi F, Wei Y et al. Necitumumab plus platinum-based chemotherapy versus chemotherapy alone as first-line treatment for stage IV non-small cell lung cancer: a meta-analysis based on randomized controlled trials. Ann Palliat Med [Internet]. 2021 [cited 2024 Jun 23];10(2):1154166\u0026ndash;1151166. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://apm.amegroups.org/article/view/51805/html\u003c/span\u003e\u003cspan address=\"https://apm.amegroups.org/article/view/51805/html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-geriatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bgtc","sideBox":"Learn more about [BMC Geriatrics](http://bmcgeriatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bgtc/default.aspx","title":"BMC Geriatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Hypomagnesemia, Venous Thromboembolism, Coagulopathy, Elderly, Hospitalized patients, Risk factor","lastPublishedDoi":"10.21203/rs.3.rs-4626225/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4626225/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground. \u003c/strong\u003eHypomagnesemia, known to be associated with physiologic stress and states of inflammation, is also known to be common in acutely ill, hospitalized patients. The potential association between hypomagnesemia and increased risk for VTE (venous thromboembolism) is not well established.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods.\u003c/strong\u003e This was a retrospective analysis of acutely ill, hospitalized elderly patients in a tertiary medical center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults. \u003c/strong\u003eA cohort of 6,428 elderly hospitalized patients (57.8% males, median age 77 years (IQR 71 - 84)) included 3,007 (46.8%) with hypomagnesemia (Mg \u0026lt; 1.8 mg/dL). Amongst the hypomagnesemia group of patients, the median age was 76 (IQR 70 – 82). There was no significant difference in the rates of background thrombophilia between both study groups (0.4% vs. 0.3%; p = 0.47). Background malignancy more common in the hypomagnesemia group (6.7% vs. 4.3%; p \u0026lt; 0.001). Usage of proton pump inhibitors was more prevalent in the hypomagnesemia group (49.9% vs. 43%; p \u0026lt; 0.001). The occurrence of VTE by 30 days of admission was significantly higher amongst patients with hypomagnesemia (3% vs. 2.1%, OR = 1.45 CI95% 1.06 – 1.99; p = 0.02). In a multivariate analysis, controlling for age, gender, background malignancy, chronic kidney disease and thrombophilia, hypomagnesemia was still, independently associated with increased occurrence of 30-days VTE [OR = 1.42, CI95% 1.04 – 1.96; P = 0.029].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions.\u003c/strong\u003eAmongst hospitalized, acutely ill, elderly patients, hypomagnesemia is independently associated with an increased risk of VTE.\u003c/p\u003e","manuscriptTitle":"Hypomagnesemia is a Risk Factor for Venous Thromboembolism (VTE) in Acutely Ill, Hospitalized Elderly Patients. A Retrospective Cohort Analysis of 6,428 Patients.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-22 10:55:10","doi":"10.21203/rs.3.rs-4626225/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-31T18:42:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-26T13:02:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"245974279538125119338189870424407992751","date":"2025-07-16T11:52:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-09T16:37:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"326027633294385661592334004996117283450","date":"2024-09-01T17:08:03+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-23T11:59:09+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-07-02T09:56:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-29T05:55:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-29T05:54:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Geriatrics","date":"2024-06-23T18:07:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-geriatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bgtc","sideBox":"Learn more about [BMC Geriatrics](http://bmcgeriatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bgtc/default.aspx","title":"BMC Geriatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cc34d7fd-fff6-4ac6-8cd9-5da0fae0db91","owner":[],"postedDate":"July 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-24T15:59:54+00:00","versionOfRecord":{"articleIdentity":"rs-4626225","link":"https://doi.org/10.1186/s12877-025-06644-8","journal":{"identity":"bmc-geriatrics","isVorOnly":false,"title":"BMC Geriatrics"},"publishedOn":"2025-11-18 15:57:03","publishedOnDateReadable":"November 18th, 2025"},"versionCreatedAt":"2024-07-22 10:55:10","video":"","vorDoi":"10.1186/s12877-025-06644-8","vorDoiUrl":"https://doi.org/10.1186/s12877-025-06644-8","workflowStages":[]},"version":"v1","identity":"rs-4626225","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4626225","identity":"rs-4626225","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}