Antithrombin III at Admission as a New Predictive Factor for Mortality in ECMO for Cardiogenic Shock Caused by Acute Myocardial Infarction

Antithrombin III at Admission as a New Predictive Factor for Mortality in ECMO for Cardiogenic Shock Caused by Acute Myocardial Infarction | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Antithrombin III at Admission as a New Predictive Factor for Mortality in ECMO for Cardiogenic Shock Caused by Acute Myocardial Infarction Jing-bin Huang, Zhuo Wei, Zhai Huang, Xiao-gang Tang, De-fu Zeng, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8827716/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Objectives: Extracorporeal membrane oxygenation (ECMO) is a technique increasingly used in the practice of intensive therapy for extracorporeal gas exchange and/or circulatory support in patients with acute respiratory and/or cardiac failure, when conventional treatment modalities are ineffective. We aimed to investigate impacts of antithrombin III at admission on ECMO outcomes in cardiogenic shockcomplicated by acute myocardial infarction. Methods: We retrospectively studied patients with acute myocardial infarctioncomplicated by cardiogenic shock undergoing ECMO in four hospitals in China. Results: The in-hospital mortality rate was 47.8% (194/406). The antithrombin III at admission of the in-hospital death group (n=194) and the survival group (n=212) were 45.70 ± 21.57 and 50.97 ± 25.37 ng/L, respectively. We decided to take 46 ng/L of antithrombin III at admission as the cut-off value for grouping and comparing the differences between the two groups. The AT III at admission＜ and ≥ 46 ng/Lgroups were similar in male gender, age, weight, Killip 3, Killip 4, hypertension, diabetes and atrial fibrillation,serum troponin, and serum creatine kinase isoenzyme. In-hospital mortalityand acute kidney injury, and serum creatinine in the AT III at admission＜46 ng/L group were significantly higher than that in the AT III at admission ≥ 46 ng/L group. By univariate and multivariate analysis, serum albumin ＜30 g/L, AT III at admission＜46 ng/L, and serum lactate were found to be related to in-hospital mortality. Conclusions: Our investigation demonstrated that low antithrombin III at admission was associated with in-hospital in cardiogenic shock secondary to acute myocardial infarction on ECMO, suggesting that monitoring AT III plasma levels may be important in the management of ECMO. Health sciences/Biomarkers Health sciences/Cardiology Health sciences/Diseases Health sciences/Medical research Antithrombin III at admission ECMO Cardiogenic Shock Acute Myocardial Infarction Figures Figure 1 Figure 2 Introduction Extracorporeal membrane oxygenation (ECMO) is a temporary circulatory and life support technique used to provide respiratory and cardiac support. Research has shown that the application of this complex life-saving measure has significantly increased in recent years. It is crucial to evaluate solutions that provide consistent ECMO support. Bleeding and thrombosis are important risks factors for ECMO supported patients; These events may be caused by the activation of procoagulant and anticoagulant factors when the catheter comes into contact with the endothelial surface of the blood vessel. [ 1 – 3 ] Therefore, the anticoagulation guidelines for extracorporeal life support recommend the use of antithrombotic therapy during ECMO, but the guidelines allow each institution to develop its own titration strategy. Heparin is the most commonly used anticoagulant in ECMO. In history, activated clotting time (ACT) has been used to determine the therapeutic effect of heparin anticoagulation during ECMO. The treatment range is generally defined as 180–220 seconds. Activated clotting time may be influenced by multiple factors, including platelet count, urine output, fibrinogen levels, body temperature, blood dilution, lack of other clotting factors, and renal replacement therapy. However, some institutions have changed their protocols and no longer rely solely on activated clotting time to determine the coagulation status during ECMO. Activated partial thromboplastin time (aPTT) is used to measure the onset time of fibrin formation in platelet poor plasma, typically used to determine the degree of heparin induced anticoagulation, but is subject to interference from high levels of factor VIII and other components such as alpha 2-macroglobulin. [ 4 – 6 ] Diffuse intravascular coagulation (DIC) is an acquired clinical syndrome characterized by systemic activation of intravascular coagulation, leading to the formation of fibrin in blood vessels. It is typically associated with severe infections, major trauma, and immune and hematological disorders. Diffuse intravascular coagulation may ultimately lead to thrombotic occlusion of blood vessels, worsening tissue oxygen supply, and is the main cause of death in critically ill patients. Generally speaking, due to the exposure of the patient's blood to the non-endothelial surface of the extracorporeal membrane oxygenation (ECMO) circuit, this non-physiological contact induces systemic inflammatory response and activation of the coagulation system. [ 7 – 10 ] In previous studies, the incidence of DIC was high, with over 40% of patients supported by ECMO; However, the prognostic role of DIC in ECMO environment is still inconclusive, as previous observational studies were conducted on specific target populations, such as septic shock or cardiac surgery patients, and the number of patients was very limited. In addition, clinical antithrombin (AT) deficiency may be caused by activated coagulation and long-term anticoagulation, impaired synthesis, and DIC, especially acquired antithrombin deficiency, which is common in ECMO supported patients. The clinical importance of monitoring AT III as a biomarker has not been fully elucidated, as studies have shown that low AT III supplementation (93.0-123.0%) does not improve clinical outcomes and prognosis in patients with acute respiratory failure receiving ECMO, although it may help reduce the imbalance between procoagulant and anticoagulant factors. [ 11 – 14 ] Limited data are available on the relationship of antithrombin (AT) III with mortality in patients receiving extracorporeal membrane oxygenation (ECMO). Thus, we investigated the association of antithrombin (AT) III with clinical outcomes in patients with cardiogenic shock caused by acute myocardial infarction undergoing ECMO. Materials and methods We conducted a retrospective cohort study on the medical records of patients with acute myocardial infarction combined with cardiogenic shock who received ECMO treatment in four hospitals in Guangxi, China from 2019 to 2023. The protocol of this study follows the guidelines set forth in the Helsinki Declaration, and the experimental protocol has been approved by the institutional review committees of four medical institutions. Eligible adult patients (aged ≥ 18 years) diagnosed with cardiogenic shock caused by acute myocardial infarction and undergoing venous arterial extracorporeal membrane oxygenation (VA-ECMO) were included in this study. Patients with stroke, previous percutaneous coronary intervention or coronary artery bypass grafting, and those who died within 24 hours of admission were excluded from this study. Definition The in-hospital all-cause mortality rate was defined as the ratio of the total number of deaths caused by various reasons during hospitalization to the number of patients. Cardiogenic shock wass defined as a clinical syndrome characterized by significant reduction in cardiac output and severe acute peripheral circulation failure, caused by extreme decline in cardiac function. Gastrointestinal bleeding in this study referred to the rupture and bleeding of gastrointestinal blood vessels between the esophagus and anus due to various reasons. This article defined it as a positive fecal occult blood test. Detection of Antithrombin III at admission AT III plasma levels were measured in the AT activity concentration of the plasma sample using the STA-R Max (Stago, France) equipment. This is a chromogenic assay-based test that measures the absorbance at 405 nm after adding bovine thrombin to a patient’s platelet-poor plasma. [15] Primary outcomes The primary outcome was in-hospital mortality. Secondary outcomes The secondary outcomes included all-cause mortality in follow-up and the incidence of complications, such as serum troponin, serum creatine kinase isoenzyme, serum lactate, serum albumin, IABP, gastrointestinal bleeding, lower limb ischemia, pump thrombosis, cerebral hemorrhage, acute kidney injury, mechanical ventilation time, ECMO time, hemodialysis time, length of ICU stay, hospital stay，frozen plasma transfusion, and red blood cells transfusion, red blood cell distribution width, PT, and all-cause mortality in follow-up. Variables We conducted an investigation on the parameters. Variables included age, serum troponin, serum creatine kinase isoenzyme, serum lactate, serum albumin, IABP, in-hospital mortality, gastrointestinal bleeding, lower limb ischemia, pump thrombosis, cerebral hemorrhage, acute kidney injury, mechanical ventilation time, ECMO time, hemodialysis time, length of ICU stay, hospital stay，frozen plasma transfusion, and red blood cells transfusion, red blood cell distribution width, PT, and all-cause mortality in follow-up. Follow-up From discharge to death or the end of the study, all surviving and discharged patients undergo echocardiography, electrocardiography, and chest X-ray examinations every 1 to 3 months. During the final follow-up, surviving patients were followed up at the outpatient department or contacted through phone or WeChat for follow-up. The routine X-ray, electrocardiogram, and echocardiogram monitoring data of discharged patients are obtained from the outpatient record system. We used multiple imputation (MI) to fill in these missing follow-up data. Statistical analyses We analyzed continuous variables using Wilcoxon rank sum test and reported them as median and interquartile range. We also presented categorical data in the form of frequency and percentage, and investigated it using chi square test or Fisher's exact test. We used logistic regression and created Kaplan Meier curves and compared them using logarithmic rank test. Cox proportional risk model was used. All tests are bilateral, and statistical significance is defined by a p-value less than 0.05. IBM SPSS 24.0 software (IBM SPSS Inc., New York, USA) was used to complete the analysis. Results 406 patients with acute myocardial infarction complicated by cardiogenic shock under ECMO were included. The in-hospital mortality rate was 47.8% (194/406). We conducted ROC analysis but did not find any positive results, so we cannot determine the cut-off value of antithrombin III. We have also consulted relevant literature, but so far we have not found any relevant publications of the cut-off value of antithrombin III. The antithrombin III at admission of the in-hospital death group (n=194) and the survival group (n=212) were 45.70 ± 21.57 and 50.97 ± 25.37 ng/L, respectively (P<0.001). We decided to take 46 ng/L of antithrombin III at admission as the cut-off value for grouping and comparing the differences between the two groups. (Figure 1) Characteristics of the population The AT III at admission＜ and ≥ 46 ng/L groups were similar in male gender, age, weight, Killip 3, Killip 4, hypertension, diabetes and atrial fibrillation, serum troponin, and serum creatine kinase isoenzyme. (all P＞0.05). Serum creatinine (196.86±106.73 vs 172.26±70.07 μmol/L, P=0.006) in the AT III at admission＜ 46 ng/L group were significantly greater than those in the AT III at admission ≥ 46 ng/L group. (Table 1) Primary Outcomes In-hospital mortality in the AT III at admission＜46 ng/L group was significantly greater than that in the AT III at admission ≥ 46 ng/L group (76.0% vs 39.5%, P＜0.001). (Table 2) Secondary Outcomes The AT III at admission＜and ≥ 46 ng/L groups were similar in gastrointestinal bleeding, lower limb ischemia, pump thrombosis, and cerebral hemorrhage (all P ＞ 0.05). (Table 2) Acute kidney injury (80.9% vs 49.8%, P＜0.001) in the AT III at admission＜46 ng/L group were significantly higher than that in the AT III at admission ≥ 46 ng/L group. Mechanical ventilation time (177.98±155.58 vs 320.41±344.14 hours, P＜0.001), ECMO time (99.91±104.64 vs 125.74±123.31 hours, P = 0.025), length of ICU stay (13.23±11.91 vs 22.09±25.82 days, P＜0.001), hospital stay (15.37±14.03 vs 30.13±24.40 days, P＜0.001), and red blood cells transfusion (6.32±6.84 vs 9.50±12.02 units, P＜0.001) in the AT III at admission＜46 ng/L group were significantly less than those in the AT III at admission ≥ 46 ng/L group. (Table 2) Both hemodialysis time and frozen plasma transfusion in the two groups were similar (both P ＞ 0.05). (Table 2) Factors related to in-hospital mortality By univariate analysis, serum albumin ＜30 g/L (OR: 2.542, 95% CI: 1.697-3.808, P＜0.001), AT III at admission＜46 ng/L (OR: 4.846, 95% CI: 3.145-7.469, P＜0.001), and serum lactate at admission (OR: 2.335, 95% CI: 1.547-3.525, P＜0.001) were found to be related to in-hospital mortality. By multivariate analyses, serum albumin ＜30 g/L (OR: 2.082, 95% CI: 1.322-3.279, P=0.002), AT III at admission＜46 ng/L (OR: 3.812, 95% CI: 2.397-6.064, P＜0.001), and serum lactate at admission (OR: 4.276, 95% CI: 2.399-7.623, P＜0.001) were found to be related to in-hospital mortality. (Table 3) Discussion We retrospectively studied patients with acute myocardial infarction complicated by cardiogenic shock undergoing ECMO in four hospitals in China. The in-hospital mortality rate was 47.8% (194/406). The antithrombin III at admission of the in-hospital death group (n = 194) and the survival group (n = 212) were 45.70 ± 21.57 and 50.97 ± 25.37 ng/L, respectively. We decided to take 46 ng/L of antithrombin III at admission as the cut-off value for grouping and comparing the differences between the two groups. In-hospital mortality and acute kidney injury, and serum creatinine in the AT III at admission<46 ng/L group were significantly higher than that in the AT III at admission ≥ 46 ng/L group. By univariate and multivariate analysis, serum albumin <30 g/L, AT III at admission<46 ng/L, and serum lactate at admission were found to be related to in-hospital mortality. Research has shown that DIC is a common outcome of severe inflammation in critically ill patients. It is reported that the incidence rate of DIC in patients receiving ECMO ranges from 41% to 50%. The initiation of ECMO is associated with immediate and complex inflammatory responses, similar to those observed in systemic inflammatory response syndrome. [ 16 – 21 ] When the patient's blood is exposed to the artificial surface of the ECMO circuit, the coagulation fibrinolysis system and inflammatory response are immediately activated. These reactions are closely related to the network of bodily fluids and cellular components, leading to DIC clinical syndrome. Several studies have evaluated the relationship between pre ECMO DIC scores and in-hospital mortality in patients undergoing ECMO. Research has shown that the pre ECMO disseminated intravascular coagulation score is associated with 90-day mortality and is an important risk factor for in-hospital mortality in patients with septic shock. In DIC patients who require vasopressors, mechanical ventilation and CRRT are used more frequently, indicating a higher severity of shock. ECMO technology has made significant progress in recent years, including hollow fiber polyethylene oxygenators, biologically passive surfaces of circuits, and enhanced pump and sleeve designs, which may have an impact on reducing the frequency of bleeding and thrombosis. [ 22 – 24 ] The anticoagulation management during ECMO in clinical practice is usually based on continuous infusion of unfractionated heparin, which strictly depends on the AT activity in the patient's plasma. AT inhibits thrombin and activates coagulation factor X; however, in clinical practice, doctors typically do not measure this level when diagnosing DIC. Studies have shown that in comparative studies of activated clotting time and anti Xa factor levels in patients receiving ECMO support for anticoagulant management evaluation, anti Xa protein measurement has been proven to be a more suitable detection method for anticoagulant monitoring than activated clotting time. According to reports, the 28-day survival rate of patients with severe AT deficiency is significantly lower than that of patients without AT deficiency. [ 25 – 27 ] AT III is associated with DIC and may be a valuable clinical indicator for predicting DIC in ECMO patients. [ 28 , 29 ] Clinical doctors have been seeking the optimal balance between anticoagulation and hemostasis in patients supported by extracorporeal circulation (ECMO). The ideal state we pursue is to limit the formation of thrombi within the ECMO circuit, which may prolong the lifespan of the ECMO circuit, reduce the risk of embolism transmission to patients, and minimize the risk of bleeding. Heparin is the most widely used anticoagulant method in ECMO support for patients. Heparin has a relatively short half-life and exerts its anticoagulant effect by binding with antithrombin (AT). Antithrombin is a potent endogenous anticoagulant, and AT is a natural glycoprotein produced by the liver, which is the main inhibitor of coagulation in the body. AT irreversibly binds to factors IIa and Xa to inhibit coagulation, and to a lesser extent inhibits coagulation by inhibiting factors IXa, XIa, and XIIa. When heparin binds to AT, it causes conformational changes in the AT molecule, exposes reaction sites, and accelerates the formation of thrombin antithrombin (TAT) complexes by over a thousand times. When patients receive ECMO treatment, the consumption of endogenous AT is caused by the contact between blood and the artificial surface of the ECMO circuit and heparin. If this consumption continues without treatment, it will lead to AT deficiency, resulting in heparin resistance. Recent studies have shown that using AT supplements to maintain normal levels of AT activity may reduce the consumption of clotting factors and platelets, as well as weaken the associated inflammatory reactions caused by insufficient anticoagulation. The artificial surface of the ECMO circuit in contact with the patient's blood activates the hemostatic system, leading to the production and consumption of TAT complexes, which also shortens the half-life of circulating AT. In the presence of heparin, the half-life of AT will be significantly shortened. [ 30 – 32 ] The medical treatment concept and technology for end-stage heart failure continue to make progress, but the number of patients requiring mechanical circulatory support (MCS) is still rapidly increasing. Mechanical circulatory support provided by extracorporeal membrane oxygenation or ventricular assist devices has become the main treatment strategy for patients with end-stage heart failure. After stable hemodynamic recovery with sufficient cardiac output supported by mechanical circulation, pre-existing comorbid multiple organ failure is often associated with poor prognosis. Treating multiple organ failure is a key measure to reverse the condition of critically ill patients and achieve good clinical outcomes. [ 33 – 35 ] Antithrombin III is entirely produced by liver cells and plays a crucial role as an endogenous anticoagulant by inhibiting thrombin, a central coagulant with multiple functions. In clinical practice, monitoring antithrombin III levels is particularly important in ECMO environments. According to research reports, the reduction of antithrombin III is associated with impaired liver microcirculation, which may further explain the important roles of "post congestion" and "pre ischemia" in liver parenchyma. In addition, studies have shown that antithrombin III also plays an important role in preventing cell apoptosis and ischemia induced inflammatory responses. In a rat ischemia-reperfusion model, treatment with antithrombin III upon portal vein admission is associated with a significant reduction in cell apoptosis and inflammation. Due to its ability to rapidly reverse thrombin induced endothelial cell rolling, but not histamine induced endothelial epithelial cell rolling, antithrombin III appears to have great potential in reducing MCS induced systemic inflammatory response syndrome (SIRS). We know that systemic inflammatory response syndrome is a clinical activation of the immune system similar to sepsis, and is a typical manifestation of end-stage long-term cardiogenic shock. Previous studies have shown that the level of antithrombin III is an independent predictor of in-hospital mortality in patients with systemic inflammatory response syndrome, and its depletion is an early sensitive biomarker for the development of systemic inflammatory response syndrome. Pathophysiological mechanisms suggest that antithrombin III plays a crucial role in anticoagulation by increasing the inactivation of thrombin, factor Xa, and factor IXa. In clinical practice, in the presence of heparin, the structure of antithrombin undergoes conformational changes, resulting in a 100-fold increase in enzyme activity. Acquired ATIII deficiency in young patients, extracorporeal circulation, ECMO, sepsis and long-term heparin treatment are common. ATIII deficiency manifests as heparin resistance, often leading to frequent and significant dose increases, making it difficult to achieve therapeutic anticoagulation goals. [ 36 – 38 ] In our study, in-hospital mortality and acute kidney injury, and serum creatinine in the AT III at admission<46 ng/L group were significantly higher than that in the AT III at admission ≥ 46 ng/L group, and AT III at admission<46 ng/L was found to be related to in-hospital mortality. Our study suggests that antithrombin, a potent endogenous anticoagulant, is an indicator of coagulation dysfunction, assessment of shock severity, prediction of clinical prognosis, and a potential target for clinical treatment. Limitations The limitations of this research comprised its retrospective design, which may lead to bias of selection due to the retrospective nature of the research. Long term recruitment of patients may have adverse effects on the accuracy of the results. Prospective randomized controlled trials are needed, and plans to reduce the incidence rate and mortality of infectious endocarditis in hospital are needed. Conclusions Our investigation demonstrated that low antithrombin III at admission was associated with in-hospital in cardiogenic shock secondary to acute myocardial infarction on ECMO, suggesting that monitoring AT III plasma levels may be important in the management of ECMO. Abbreviations AT III = Antithrombin III at admission; CI = confidence interval; CS = Cardiogenic shock; cum. = cumulative; ECPR = extracorporeal cardiopulmonary resuscitation; IBM = International Business Machines; ICU = intensive care unit; OR = odds ratio; SPSS = Statistical Package for Social Sciences; VA ECMO = venoarterial extracorporeal membrane oxygenation; vs = versus. Declarations Author Contribution Author ContributionsJing-bin Huang and Zhai Huang designed the research study. Zhuo Wei , Xiao-gang Tang, De-fu Zeng, Ke-qiang Huang, and Jian Li performed the research. Xiao-gang Tang, De-fu Zeng, Ke-qiang Huang, and Jian Li analyzed the data. All authors read and approved the final manuscript. Ethical Approval The experiment protocol for involving humans was in accordance to Helsinki Statement and national guidelines and was approved by the Medical Ethics Committee of The People’s Hospital of Guangxi Zhuang Autonomous Region (no. PGRT0216), the Medical Ethics Committee of The Second People's Hospital of Qinzhou City (no. QZ201811), the Medical Ethics Committee of The People's Hospital of Lingshan (no. L1826), and the Medical Ethics Committee of The People's Hospital of Pubei (no.PB 201826). Informed consent was obtained from all subjects and/or their legal guardian(s). Funding This work was supported by the Natural Science Foundation of China (No: 81360014), the Natural Science Foundation of Guangxi (No: 2014GXNSFAA118234), the Guangxi key scientific and technological project (No: 2013BC26236), and the Projects in Guangxi Health Department (No: GZPT13-27). Availability of Data and Materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Clinical trial number Not applicable. Competing interests None. Acknowledgments None. References Gerke, A. K. et al. 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Baseline patient characteristics (n=406) Variable AT III at admission＜46 ng/L group (n=183) AT III at admission ≥ 46 ng/L group (n=223) P value Male gender, n (%) 154 (84.2%) 191 (85.7%) 0.674 Age, years 61.852±9.3665 61.596±8.7605 0.777 Weight, kg 65.021±5.7094 65.356±5.8807 0.563 Killip classification Killip 3, n (%) 14 (7.7%) 19 (8.5%) 0.750 Killip 4, n (%) 169 (92.3%) 204 (91.5%) 0.750 Hypertension, n (%) 49 (26.8%) 55 (24.7%) 0.628 Diabetes, n (%) 51 (27.9%) 58 (26.0%) 0.674 Atrial fibrillation, n (%) 8 (4.4%) 13 (5.8%) 0.509 Serum creatinine, μmol/L 196.86±106.73 172.26±70.07 0.006 Serum troponin, ng/mL 5.387±3.937 5.20±3.9056 0.638 Serum creatine kinase isoenzyme, U/L 120.80±123.04 109.61±125.52 0.368 Table 2 . Endpoints comparison between the two groups (n=406) Variable AT III at admission＜46 ng/L group (n=183) AT III at admission ≥ 46 ng/L group (n=223) P In-hospital mortality, n (%) 139 (76.0%) 88 (39.5%) ＜0.001 Gastrointestinal bleeding, n (%) 111 (60.7%) 153 (68.6%) 0.094 Lower limb ischemia, n (%) 21 (11.5%) 16 (7.2%) 0.134 Pump thrombosis, n (%) 20 (10.9%) 32 (14.3%) 0.305 Cerebral hemorrhage, n (%) 7 (3.8%) 8 (3.6%) 0.899 Acute kidney injury, n (%) 148 (80.9%) 111 (49.8%) ＜0.001 Mechanical ventilation time, hours 177.98±155.58 320.41±344.14 ＜0.001 ECMO time, hours 99.91±104.64 125.74±123.31 0.025 Hemodialysis time, hours 100.10±141.54 119.03±235.85 0.341 Length of ICU stay, days 13.23±11.91 22.09±25.82 ＜0.001 Hospital stay, days 15.37±14.03 30.13±24.40 ＜0.001 Frozen plasma transfusion, ml 1442.95±1954.96 1751.88±1613.11 0.082 Red blood cells transfusion, units 6.32±6.84 9.50±12.02 0.002 Table 3. Factors related to in-hospital mortality (n=406) Model OR 95% CI P value Univariate analysis Serum albumin ＜30 g/L 2.542 1.697-3.808 ＜0.001 AT III at admission＜46 ng/L 4.846 3.145-7.469 ＜0.001 Serum lactate at admission 2.335 1.547-3.525 ＜0.001 Multivariate analysis Serum albumin ＜30 g/L 2.082 1.322-3.279 0.002 AT III at admission＜46 ng/L 3.812 2.397-6.064 ＜0.001 Serum lactate at admission 4.276 2.399-7.623 ＜0.001 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 24 Mar, 2026 Reviews received at journal 16 Mar, 2026 Reviews received at journal 13 Mar, 2026 Reviewers agreed at journal 11 Mar, 2026 Reviewers agreed at journal 10 Mar, 2026 Reviews received at journal 07 Mar, 2026 Reviewers agreed at journal 07 Mar, 2026 Reviewers invited by journal 03 Mar, 2026 Editor invited by journal 16 Feb, 2026 Editor assigned by journal 11 Feb, 2026 Submission checks completed at journal 11 Feb, 2026 First submitted to journal 09 Feb, 2026 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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Huang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYBACA4YzDAcSDGzk+NkbGx9+IFIL44MHFWnGkj2Hm40liNPCw2z44MzhxA030tsEeIjRYs549phEYhszY8PNh20MEgx2croNBLRYNpxLA2phY2acndj2oIAh2djsACGHHThjBtTCw8YsndhuIMFwIHEbkVokeNgkDwJJIrUYGyScMZDgkWAkWsu5xAcJFQlAPYnAQDYgxi83zh44+MPgf/3+48cfPvxQYSdHUAuDBIoKA0LKQYC/gRhVo2AUjIJRMKIBACQHSlGIJy1ZAAAAAElFTkSuQmCC","orcid":"","institution":"The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Jing-bin","middleName":"","lastName":"Huang","suffix":""},{"id":601300980,"identity":"9bb93770-d1c5-4269-946b-5f09d92f8312","order_by":1,"name":"Zhuo Wei","email":"","orcid":"","institution":"Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Zhuo","middleName":"","lastName":"Wei","suffix":""},{"id":601300981,"identity":"1b38d0d3-8d35-4b0d-a64c-86ab283e2a34","order_by":2,"name":"Zhai Huang","email":"","orcid":"","institution":"The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Zhai","middleName":"","lastName":"Huang","suffix":""},{"id":601300982,"identity":"c6fad2ee-339d-4ddb-a441-ad06befc5862","order_by":3,"name":"Xiao-gang Tang","email":"","orcid":"","institution":"The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Xiao-gang","middleName":"","lastName":"Tang","suffix":""},{"id":601300983,"identity":"61bf4cf5-6485-4079-a8bb-2bcbe9b1997d","order_by":4,"name":"De-fu Zeng","email":"","orcid":"","institution":"The Second People's Hospital of Qinzhou City","correspondingAuthor":false,"prefix":"","firstName":"De-fu","middleName":"","lastName":"Zeng","suffix":""},{"id":601300984,"identity":"42099e24-4dc6-45fa-ab9a-3e44556af699","order_by":5,"name":"Ke-qiang Huang","email":"","orcid":"","institution":"The People's Hospital of Lingshan","correspondingAuthor":false,"prefix":"","firstName":"Ke-qiang","middleName":"","lastName":"Huang","suffix":""},{"id":601300985,"identity":"0eeb8653-7ade-4c81-afcc-af22e735f6bf","order_by":6,"name":"Jian Li","email":"","orcid":"","institution":"The People's Hospital of Pubei","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2026-02-09 08:23:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8827716/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8827716/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104204020,"identity":"ce3bbd22-06e6-4507-8a91-d5fd5d6bf7fb","added_by":"auto","created_at":"2026-03-09 06:26:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":64769,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of patients\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8827716/v1/6b6bf63c52f1f4ffe6d02053.png"},{"id":104204037,"identity":"649f8827-da03-42ba-a49a-bcbecaca7c6d","added_by":"auto","created_at":"2026-03-09 06:26:59","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":41253,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve for survival\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8827716/v1/44a3d27903e0b0e9400fcf14.png"},{"id":104204067,"identity":"975871ad-5308-4f09-b30e-04c68e856337","added_by":"auto","created_at":"2026-03-09 06:27:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":772091,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8827716/v1/fec65d07-1b74-4662-bce9-ad471c0ae839.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eAntithrombin III at Admission as a New Predictive Factor for Mortality in ECMO for Cardiogenic Shock Caused by Acute Myocardial Infarction\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eExtracorporeal membrane oxygenation (ECMO) is a temporary circulatory and life support technique used to provide respiratory and cardiac support. Research has shown that the application of this complex life-saving measure has significantly increased in recent years. It is crucial to evaluate solutions that provide consistent ECMO support. Bleeding and thrombosis are important risks factors for ECMO supported patients; These events may be caused by the activation of procoagulant and anticoagulant factors when the catheter comes into contact with the endothelial surface of the blood vessel. [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Therefore, the anticoagulation guidelines for extracorporeal life support recommend the use of antithrombotic therapy during ECMO, but the guidelines allow each institution to develop its own titration strategy. Heparin is the most commonly used anticoagulant in ECMO. In history, activated clotting time (ACT) has been used to determine the therapeutic effect of heparin anticoagulation during ECMO. The treatment range is generally defined as 180\u0026ndash;220 seconds. Activated clotting time may be influenced by multiple factors, including platelet count, urine output, fibrinogen levels, body temperature, blood dilution, lack of other clotting factors, and renal replacement therapy. However, some institutions have changed their protocols and no longer rely solely on activated clotting time to determine the coagulation status during ECMO. Activated partial thromboplastin time (aPTT) is used to measure the onset time of fibrin formation in platelet poor plasma, typically used to determine the degree of heparin induced anticoagulation, but is subject to interference from high levels of factor VIII and other components such as alpha 2-macroglobulin. [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eDiffuse intravascular coagulation (DIC) is an acquired clinical syndrome characterized by systemic activation of intravascular coagulation, leading to the formation of fibrin in blood vessels. It is typically associated with severe infections, major trauma, and immune and hematological disorders. Diffuse intravascular coagulation may ultimately lead to thrombotic occlusion of blood vessels, worsening tissue oxygen supply, and is the main cause of death in critically ill patients. Generally speaking, due to the exposure of the patient's blood to the non-endothelial surface of the extracorporeal membrane oxygenation (ECMO) circuit, this non-physiological contact induces systemic inflammatory response and activation of the coagulation system. [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] In previous studies, the incidence of DIC was high, with over 40% of patients supported by ECMO; However, the prognostic role of DIC in ECMO environment is still inconclusive, as previous observational studies were conducted on specific target populations, such as septic shock or cardiac surgery patients, and the number of patients was very limited. In addition, clinical antithrombin (AT) deficiency may be caused by activated coagulation and long-term anticoagulation, impaired synthesis, and DIC, especially acquired antithrombin deficiency, which is common in ECMO supported patients. The clinical importance of monitoring AT III as a biomarker has not been fully elucidated, as studies have shown that low AT III supplementation (93.0-123.0%) does not improve clinical outcomes and prognosis in patients with acute respiratory failure receiving ECMO, although it may help reduce the imbalance between procoagulant and anticoagulant factors. [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eLimited data are available on the relationship of antithrombin (AT) III with mortality in patients receiving extracorporeal membrane oxygenation (ECMO). Thus, we investigated the association of antithrombin (AT) III with clinical outcomes in patients with cardiogenic shock caused by acute myocardial infarction undergoing ECMO.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eWe conducted a retrospective cohort study on the medical records of patients with acute myocardial infarction combined with cardiogenic shock who received ECMO treatment in four hospitals in Guangxi, China from 2019 to 2023. The protocol of this study follows the guidelines set forth in the Helsinki Declaration, and the experimental protocol has been approved by the institutional review committees of four medical institutions. Eligible adult patients (aged \u0026ge; 18 years) diagnosed with cardiogenic shock caused by acute myocardial infarction and undergoing venous arterial extracorporeal membrane oxygenation (VA-ECMO) were included in this study. Patients with stroke, previous percutaneous coronary intervention or coronary artery bypass grafting, and those who died within 24 hours of admission were excluded from this study. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinition \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe in-hospital all-cause mortality rate was defined as the ratio of the total number of deaths caused by various reasons during hospitalization to the number of patients. \u003c/p\u003e\n\u003cp\u003eCardiogenic shock wass defined as a clinical syndrome characterized by significant reduction in cardiac output and severe acute peripheral circulation failure, caused by extreme decline in cardiac function. \u003c/p\u003e\n\u003cp\u003eGastrointestinal bleeding in this study referred to the rupture and bleeding of gastrointestinal blood vessels between the esophagus and anus due to various reasons. This article defined it as a positive fecal occult blood test. \u003c/p\u003e\n\u003cp\u003eDetection of Antithrombin III at admission\u003c/p\u003e\n\u003cp\u003eAT III plasma levels were measured in the AT activity concentration of the plasma sample using the STA-R Max (Stago, France) equipment. This is a chromogenic assay-based test that measures the absorbance at 405 nm after adding bovine thrombin to a patient\u0026rsquo;s platelet-poor plasma. [15]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome was in-hospital mortality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe secondary outcomes included all-cause mortality in follow-up and the incidence of complications, such as serum troponin, serum creatine kinase isoenzyme, serum lactate, serum albumin, IABP, gastrointestinal bleeding, lower limb ischemia, pump thrombosis, cerebral hemorrhage, acute kidney injury, mechanical ventilation time, ECMO time, hemodialysis time, length of ICU stay, hospital stay，frozen plasma transfusion, and red blood cells transfusion, red blood cell distribution width, PT, and all-cause mortality in follow-up. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted an investigation on the parameters. Variables included age, serum troponin, serum creatine kinase isoenzyme, serum lactate, serum albumin, IABP, in-hospital mortality, gastrointestinal bleeding, lower limb ischemia, pump thrombosis, cerebral hemorrhage, acute kidney injury, mechanical ventilation time, ECMO time, hemodialysis time, length of ICU stay, hospital stay，frozen plasma transfusion, and red blood cells transfusion, red blood cell distribution width, PT, and all-cause mortality in follow-up. \u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFollow-up\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom discharge to death or the end of the study, all surviving and discharged patients undergo echocardiography, electrocardiography, and chest X-ray examinations every 1 to 3 months. During the final follow-up, surviving patients were followed up at the outpatient department or contacted through phone or WeChat for follow-up. The routine X-ray, electrocardiogram, and echocardiogram monitoring data of discharged patients are obtained from the outpatient record system. We used multiple imputation (MI) to fill in these missing follow-up data.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eStatistical analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe analyzed continuous variables using Wilcoxon rank sum test and reported them as median and interquartile range. We also presented categorical data in the form of frequency and percentage, and investigated it using chi square test or Fisher\u0026apos;s exact test. We used logistic regression and created Kaplan Meier curves and compared them using logarithmic rank test. Cox proportional risk model was used. All tests are bilateral, and statistical significance is defined by a p-value less than 0.05. IBM SPSS 24.0 software (IBM SPSS Inc., New York, USA) was used to complete the analysis.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e406 patients with acute myocardial infarction complicated by cardiogenic shock under ECMO were included. The in-hospital mortality rate was 47.8% (194/406). We conducted ROC analysis but did not find any positive results, so we cannot determine the cut-off value of antithrombin III. We have also consulted relevant literature, but so far we have not found any relevant publications of the cut-off value of antithrombin III. The antithrombin III at admission of the in-hospital death group (n=194) and the survival group (n=212) were 45.70 \u0026plusmn; 21.57 and 50.97 \u0026plusmn; 25.37 ng/L, respectively (P\u0026lt;0.001). We decided to take 46 ng/L of antithrombin III at admission as the cut-off value for grouping and comparing the differences between the two groups. (Figure 1) \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCharacteristics of the population \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe AT III at admission＜ and \u0026ge; 46 ng/L groups were similar in male gender, age, weight, Killip 3, Killip 4, hypertension, diabetes and atrial fibrillation, serum troponin, and serum creatine kinase isoenzyme. (all P＞0.05). \u003c/p\u003e\n\u003cp\u003eSerum creatinine (196.86\u0026plusmn;106.73 vs 172.26\u0026plusmn;70.07\u003cem\u003e \u003c/em\u003e\u0026mu;mol/L, P=0.006) in the AT III at admission＜ 46 ng/L group were significantly greater than those in the AT III at admission \u0026ge; 46 ng/L group. (Table 1) \u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePrimary Outcomes \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn-hospital mortality in the AT III at admission＜46 ng/L group was significantly greater than that in the AT III at admission \u0026ge; 46 ng/L group (76.0% vs 39.5%, P＜0.001). (Table 2)\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eSecondary Outcomes \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe AT III at admission＜and \u0026ge; 46 ng/L groups were similar in gastrointestinal bleeding, lower limb ischemia, pump thrombosis, and cerebral hemorrhage (all P ＞ 0.05). (Table 2) \u003c/p\u003e\n\u003cp\u003eAcute kidney injury (80.9% vs 49.8%, P＜0.001) in the AT III at admission＜46 ng/L group were significantly higher than that in the AT III at admission \u0026ge; 46 ng/L group. Mechanical ventilation time (177.98\u0026plusmn;155.58 vs 320.41\u0026plusmn;344.14\u003cem\u003e \u003c/em\u003ehours, P＜0.001), ECMO time (99.91\u0026plusmn;104.64 vs 125.74\u0026plusmn;123.31\u003cem\u003e \u003c/em\u003ehours, P = 0.025), length of ICU stay (13.23\u0026plusmn;11.91 vs 22.09\u0026plusmn;25.82\u003cem\u003e \u003c/em\u003edays, P＜0.001), hospital stay (15.37\u0026plusmn;14.03 vs 30.13\u0026plusmn;24.40\u003cem\u003e \u003c/em\u003edays, P＜0.001), and red blood cells transfusion (6.32\u0026plusmn;6.84 vs 9.50\u0026plusmn;12.02 units, P＜0.001) in the AT III at admission＜46 ng/L group were significantly less than those in the AT III at admission \u0026ge; 46 ng/L group. (Table 2) Both hemodialysis time and frozen plasma transfusion in the two groups were similar (both P ＞ 0.05). (Table 2)\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFactors \u003c/strong\u003e\u003cstrong\u003erelated to\u003c/strong\u003e\u003cstrong\u003e in-hospital mortality\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBy univariate analysis, serum albumin ＜30 g/L (OR: 2.542, 95% CI: 1.697-3.808, P＜0.001), AT III at admission＜46 ng/L (OR: 4.846, 95% CI: 3.145-7.469, P＜0.001), and serum lactate at admission (OR: 2.335, 95% CI: 1.547-3.525, P＜0.001) were found to be related to in-hospital mortality. By multivariate analyses, serum albumin ＜30 g/L (OR: 2.082, 95% CI: 1.322-3.279, P=0.002), AT III at admission＜46 ng/L (OR: 3.812, 95% CI: 2.397-6.064, P＜0.001), and serum lactate at admission (OR: 4.276, 95% CI: 2.399-7.623, P＜0.001) were found to be related to in-hospital mortality. (Table 3)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe retrospectively studied patients with acute myocardial infarction complicated by cardiogenic shock undergoing ECMO in four hospitals in China. The in-hospital mortality rate was 47.8% (194/406). The antithrombin III at admission of the in-hospital death group (n\u0026thinsp;=\u0026thinsp;194) and the survival group (n\u0026thinsp;=\u0026thinsp;212) were 45.70\u0026thinsp;\u0026plusmn;\u0026thinsp;21.57 and 50.97\u0026thinsp;\u0026plusmn;\u0026thinsp;25.37 ng/L, respectively. We decided to take 46 ng/L of antithrombin III at admission as the cut-off value for grouping and comparing the differences between the two groups. In-hospital mortality and acute kidney injury, and serum creatinine in the AT III at admission\u0026lt;46 ng/L group were significantly higher than that in the AT III at admission\u0026thinsp;\u0026ge;\u0026thinsp;46 ng/L group. By univariate and multivariate analysis, serum albumin \u0026lt;30 g/L, AT III at admission\u0026lt;46 ng/L, and serum lactate at admission were found to be related to in-hospital mortality.\u003c/p\u003e \u003cp\u003eResearch has shown that DIC is a common outcome of severe inflammation in critically ill patients. It is reported that the incidence rate of DIC in patients receiving ECMO ranges from 41% to 50%. The initiation of ECMO is associated with immediate and complex inflammatory responses, similar to those observed in systemic inflammatory response syndrome. [\u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] When the patient's blood is exposed to the artificial surface of the ECMO circuit, the coagulation fibrinolysis system and inflammatory response are immediately activated. These reactions are closely related to the network of bodily fluids and cellular components, leading to DIC clinical syndrome. Several studies have evaluated the relationship between pre ECMO DIC scores and in-hospital mortality in patients undergoing ECMO. Research has shown that the pre ECMO disseminated intravascular coagulation score is associated with 90-day mortality and is an important risk factor for in-hospital mortality in patients with septic shock. In DIC patients who require vasopressors, mechanical ventilation and CRRT are used more frequently, indicating a higher severity of shock. ECMO technology has made significant progress in recent years, including hollow fiber polyethylene oxygenators, biologically passive surfaces of circuits, and enhanced pump and sleeve designs, which may have an impact on reducing the frequency of bleeding and thrombosis. [\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe anticoagulation management during ECMO in clinical practice is usually based on continuous infusion of unfractionated heparin, which strictly depends on the AT activity in the patient's plasma. AT inhibits thrombin and activates coagulation factor X; however, in clinical practice, doctors typically do not measure this level when diagnosing DIC. Studies have shown that in comparative studies of activated clotting time and anti Xa factor levels in patients receiving ECMO support for anticoagulant management evaluation, anti Xa protein measurement has been proven to be a more suitable detection method for anticoagulant monitoring than activated clotting time. According to reports, the 28-day survival rate of patients with severe AT deficiency is significantly lower than that of patients without AT deficiency. [\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] AT III is associated with DIC and may be a valuable clinical indicator for predicting DIC in ECMO patients. [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eClinical doctors have been seeking the optimal balance between anticoagulation and hemostasis in patients supported by extracorporeal circulation (ECMO). The ideal state we pursue is to limit the formation of thrombi within the ECMO circuit, which may prolong the lifespan of the ECMO circuit, reduce the risk of embolism transmission to patients, and minimize the risk of bleeding. Heparin is the most widely used anticoagulant method in ECMO support for patients. Heparin has a relatively short half-life and exerts its anticoagulant effect by binding with antithrombin (AT). Antithrombin is a potent endogenous anticoagulant, and AT is a natural glycoprotein produced by the liver, which is the main inhibitor of coagulation in the body. AT irreversibly binds to factors IIa and Xa to inhibit coagulation, and to a lesser extent inhibits coagulation by inhibiting factors IXa, XIa, and XIIa. When heparin binds to AT, it causes conformational changes in the AT molecule, exposes reaction sites, and accelerates the formation of thrombin antithrombin (TAT) complexes by over a thousand times. When patients receive ECMO treatment, the consumption of endogenous AT is caused by the contact between blood and the artificial surface of the ECMO circuit and heparin. If this consumption continues without treatment, it will lead to AT deficiency, resulting in heparin resistance. Recent studies have shown that using AT supplements to maintain normal levels of AT activity may reduce the consumption of clotting factors and platelets, as well as weaken the associated inflammatory reactions caused by insufficient anticoagulation. The artificial surface of the ECMO circuit in contact with the patient's blood activates the hemostatic system, leading to the production and consumption of TAT complexes, which also shortens the half-life of circulating AT. In the presence of heparin, the half-life of AT will be significantly shortened. [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe medical treatment concept and technology for end-stage heart failure continue to make progress, but the number of patients requiring mechanical circulatory support (MCS) is still rapidly increasing. Mechanical circulatory support provided by extracorporeal membrane oxygenation or ventricular assist devices has become the main treatment strategy for patients with end-stage heart failure. After stable hemodynamic recovery with sufficient cardiac output supported by mechanical circulation, pre-existing comorbid multiple organ failure is often associated with poor prognosis. Treating multiple organ failure is a key measure to reverse the condition of critically ill patients and achieve good clinical outcomes. [\u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAntithrombin III is entirely produced by liver cells and plays a crucial role as an endogenous anticoagulant by inhibiting thrombin, a central coagulant with multiple functions. In clinical practice, monitoring antithrombin III levels is particularly important in ECMO environments. According to research reports, the reduction of antithrombin III is associated with impaired liver microcirculation, which may further explain the important roles of \"post congestion\" and \"pre ischemia\" in liver parenchyma. In addition, studies have shown that antithrombin III also plays an important role in preventing cell apoptosis and ischemia induced inflammatory responses. In a rat ischemia-reperfusion model, treatment with antithrombin III upon portal vein admission is associated with a significant reduction in cell apoptosis and inflammation. Due to its ability to rapidly reverse thrombin induced endothelial cell rolling, but not histamine induced endothelial epithelial cell rolling, antithrombin III appears to have great potential in reducing MCS induced systemic inflammatory response syndrome (SIRS). We know that systemic inflammatory response syndrome is a clinical activation of the immune system similar to sepsis, and is a typical manifestation of end-stage long-term cardiogenic shock. Previous studies have shown that the level of antithrombin III is an independent predictor of in-hospital mortality in patients with systemic inflammatory response syndrome, and its depletion is an early sensitive biomarker for the development of systemic inflammatory response syndrome. Pathophysiological mechanisms suggest that antithrombin III plays a crucial role in anticoagulation by increasing the inactivation of thrombin, factor Xa, and factor IXa. In clinical practice, in the presence of heparin, the structure of antithrombin undergoes conformational changes, resulting in a 100-fold increase in enzyme activity. Acquired ATIII deficiency in young patients, extracorporeal circulation, ECMO, sepsis and long-term heparin treatment are common. ATIII deficiency manifests as heparin resistance, often leading to frequent and significant dose increases, making it difficult to achieve therapeutic anticoagulation goals. [\u003cspan additionalcitationids=\"CR37\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn our study, in-hospital mortality and acute kidney injury, and serum creatinine in the AT III at admission\u0026lt;46 ng/L group were significantly higher than that in the AT III at admission\u0026thinsp;\u0026ge;\u0026thinsp;46 ng/L group, and AT III at admission\u0026lt;46 ng/L was found to be related to in-hospital mortality. Our study suggests that antithrombin, a potent endogenous anticoagulant, is an indicator of coagulation dysfunction, assessment of shock severity, prediction of clinical prognosis, and a potential target for clinical treatment.\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThe limitations of this research comprised its retrospective design, which may lead to bias of selection due to the retrospective nature of the research. Long term recruitment of patients may have adverse effects on the accuracy of the results. Prospective randomized controlled trials are needed, and plans to reduce the incidence rate and mortality of infectious endocarditis in hospital are needed.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur investigation demonstrated that low antithrombin III at admission was associated with in-hospital in cardiogenic shock secondary to acute myocardial infarction on ECMO, suggesting that monitoring AT III plasma levels may be important in the management of ECMO.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAT III = Antithrombin III at admission; CI = confidence interval; CS = Cardiogenic shock; cum. = cumulative; ECPR = extracorporeal cardiopulmonary resuscitation; IBM = International Business Machines; ICU = intensive care unit; OR = odds ratio; SPSS = Statistical Package for Social Sciences; VA ECMO = venoarterial extracorporeal membrane oxygenation; vs = versus.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAuthor ContributionsJing-bin Huang and Zhai Huang designed the research study. Zhuo Wei , Xiao-gang Tang, De-fu Zeng, Ke-qiang Huang, and Jian Li performed the research. Xiao-gang Tang, De-fu Zeng, Ke-qiang Huang, and Jian Li analyzed the data. All authors read and approved the final manuscript.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthical Approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe experiment protocol for involving humans was in accordance to Helsinki Statement and national guidelines and was approved by the Medical Ethics Committee of The People\u0026rsquo;s Hospital of Guangxi Zhuang Autonomous Region (no. PGRT0216), the Medical Ethics Committee of The Second People\u0026apos;s Hospital of Qinzhou City (no. QZ201811), the Medical Ethics Committee of \u0026nbsp;The People\u0026apos;s Hospital of Lingshan (no. L1826), and the Medical Ethics Committee of The People\u0026apos;s Hospital of Pubei (no.PB 201826). Informed consent was obtained from all subjects and/or their legal guardian(s).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Natural Science Foundation of China (No: 81360014), the Natural Science Foundation of Guangxi (No: 2014GXNSFAA118234), the Guangxi key scientific and technological project (No: 2013BC26236), and the Projects in Guangxi Health Department (No: GZPT13-27).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGerke, A. 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Hereditary and acquired anti thrombin deficiency: epidemiology, pathogenesis and treatment options. \u003cem\u003eDrugs\u003c/em\u003e \u003cb\u003e67\u003c/b\u003e (10), 1429\u0026ndash;1440 (2007).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eColman, E. et al. Evaluation of a heparin monitoring protocol for extracorporeal membrane oxygenation and review of the literature. \u003cem\u003eJ. Thorac. Dis.\u003c/em\u003e \u003cb\u003e11\u003c/b\u003e (8), 3325\u0026ndash;3335 (2019).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1\u003cstrong\u003e.\u003c/strong\u003e Baseline patient characteristics (n=406)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"541\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003eAT III at admission＜46 ng/L group (n=183)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003eAT III at admission \u0026ge; 46 ng/L group (n=223)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eMale gender, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e154 (84.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e191 (85.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.674\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eAge, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e61.852\u0026plusmn;9.3665\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e61.596\u0026plusmn;8.7605\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.777\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eWeight, kg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e65.021\u0026plusmn;5.7094\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e65.356\u0026plusmn;5.8807\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.563\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eKillip classification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eKillip 3, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e14 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e19 (8.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.750\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eKillip 4, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e169 (92.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e204 (91.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.750\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eHypertension, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e49 (26.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e55 (24.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.628\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eDiabetes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e51 (27.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e58 (26.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.674\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eAtrial fibrillation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e8 (4.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e13 (5.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.509\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eSerum creatinine, \u0026mu;mol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e196.86\u0026plusmn;106.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e172.26\u0026plusmn;70.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eSerum troponin, ng/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e5.387\u0026plusmn;3.937\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e5.20\u0026plusmn;3.9056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.638\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eSerum creatine kinase isoenzyme, U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e120.80\u0026plusmn;123.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e109.61\u0026plusmn;125.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.368\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2\u003cstrong\u003e.\u003c/strong\u003e Endpoints comparison between the two groups (n=406)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"548\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003eAT III at admission＜46 ng/L group (n=183)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003eAT III at admission \u0026ge; 46 ng/L group (n=223)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eIn-hospital mortality, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;139 (76.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e88 (39.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eGastrointestinal bleeding, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;111 (60.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e153 (68.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.094\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eLower limb ischemia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;21 (11.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e16 (7.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.134\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003ePump thrombosis, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;20 (10.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e32 (14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.305\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eCerebral hemorrhage, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;7 (3.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e8 (3.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.899\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eAcute kidney injury, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp;148 (80.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e111 (49.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eMechanical ventilation time, hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e177.98\u0026plusmn;155.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e320.41\u0026plusmn;344.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eECMO time, hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e99.91\u0026plusmn;104.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e125.74\u0026plusmn;123.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eHemodialysis time, hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e100.10\u0026plusmn;141.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e119.03\u0026plusmn;235.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.341\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eLength of ICU stay, days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e13.23\u0026plusmn;11.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e22.09\u0026plusmn;25.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eHospital stay, days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e15.37\u0026plusmn;14.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e30.13\u0026plusmn;24.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eFrozen plasma transfusion, ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e1442.95\u0026plusmn;1954.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e1751.88\u0026plusmn;1613.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.082\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003eRed blood cells transfusion, units\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003e6.32\u0026plusmn;6.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e9.50\u0026plusmn;12.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 3. Factors related to in-hospital mortality (n=406)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"574\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eModel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 574px;\"\u003e\n \u003cp\u003eUnivariate analysis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eSerum albumin ＜30 g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e2.542\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e1.697-3.808\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eAT III at admission＜46 ng/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e4.846\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e3.145-7.469\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eSerum lactate at admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e2.335\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e1.547-3.525\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 574px;\"\u003e\n \u003cp\u003eMultivariate analysis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eSerum albumin ＜30 g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e2.082\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e1.322-3.279\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eAT III at admission＜46 ng/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e3.812\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e2.397-6.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eSerum lactate at admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e4.276\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e2.399-7.623\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Antithrombin III at admission, ECMO, Cardiogenic Shock, Acute Myocardial Infarction","lastPublishedDoi":"10.21203/rs.3.rs-8827716/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8827716/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives:\u003c/strong\u003e Extracorporeal membrane oxygenation (ECMO) is a technique increasingly used in the practice of intensive therapy for extracorporeal gas exchange and/or circulatory support in patients with acute respiratory and/or cardiac failure, when conventional treatment modalities are ineffective. We aimed to investigate impacts of antithrombin III at admission on ECMO outcomes in cardiogenic shockcomplicated by acute myocardial infarction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We retrospectively studied patients with acute myocardial infarctioncomplicated by cardiogenic shock undergoing ECMO in four hospitals in China.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe in-hospital mortality rate was 47.8% (194/406). The antithrombin III at admission of the in-hospital death group (n=194) and the survival group (n=212) were 45.70 ± 21.57 and 50.97 ± 25.37 ng/L, respectively. We decided to take 46 ng/L of antithrombin III at admission as the cut-off value for grouping and comparing the differences between the two groups. The AT III at admission＜ and ≥ 46 ng/Lgroups were similar in male gender, age, weight, Killip 3, Killip 4, hypertension, diabetes and atrial fibrillation,serum troponin, and \u0026nbsp;serum creatine kinase isoenzyme. In-hospital mortalityand acute kidney injury, and serum creatinine in the AT III at admission＜46 ng/L group were significantly higher than that in the AT III at admission ≥ 46 ng/L group. By univariate and multivariate analysis, serum albumin ＜30 g/L, AT III at admission＜46 ng/L, and serum lactate were found to be related to in-hospital mortality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eOur investigation demonstrated that low antithrombin III at admission was associated with in-hospital in cardiogenic shock secondary to acute myocardial infarction on ECMO, suggesting that monitoring AT III plasma levels may be important in the management of ECMO.\u003c/p\u003e","manuscriptTitle":"Antithrombin III at Admission as a New Predictive Factor for Mortality in ECMO for Cardiogenic Shock Caused by Acute Myocardial Infarction","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-09 06:25:04","doi":"10.21203/rs.3.rs-8827716/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-24T09:34:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-16T08:54:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-13T11:08:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"68200608190590571170332438086228135110","date":"2026-03-11T07:22:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"118485495046177873317695093642988187331","date":"2026-03-11T00:49:12+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-07T17:56:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"34437863628244133421723501114352735136","date":"2026-03-07T17:17:46+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-03T11:02:48+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-16T11:05:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-11T14:31:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-11T14:27:14+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-02-09T08:11:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b7ef6728-363a-4b28-85d8-d455a2eb6f5d","owner":[],"postedDate":"March 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":64070549,"name":"Health sciences/Biomarkers"},{"id":64070550,"name":"Health sciences/Cardiology"},{"id":64070551,"name":"Health sciences/Diseases"},{"id":64070552,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2026-05-11T14:54:09+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-09 06:25:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8827716","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8827716","identity":"rs-8827716","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}