{"paper_id":"8ba9f176-429d-4616-ad11-8845f7c251e3","body_text":"The Risk of Upper Gastrointestinal Bleeding and Coagulopathy in IBD Patients with Cirrhosis | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Risk of Upper Gastrointestinal Bleeding and Coagulopathy in IBD Patients with Cirrhosis Medha Rajamanuri, Sreeram Pannala, Sophia Dar, Anirudh Danduboyina, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4266765/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction : In cirrhotic patients, systemic inflammation disrupts the delicate balance of hemostatic variables, akin to what occurs in inflammatory bowel disease (IBD), potentially resulting in a shift towards either a procoagulant or anticoagulant state. Current guidelines advocating for anticoagulation use in hospitalized IBD patients lack strong evidence, and there is a notable absence of guidelines tailored specifically for those with underlying cirrhosis. This study seeks to explore how underlying cirrhosis impacts the risk of coagulopathy and gastrointestinal bleeding in IBD patients, aiming to provide insights for making well-informed decisions regarding anticoagulation therapy. Patients and Methods : Utilizing the National Inpatient Sample database, we identified hospitalizations with a primary or secondary diagnosis of IBD and cirrhosis based on ICD-10 codes from 2016 to 2020. This retrospective cohort study excluded pregnant women, patients requiring chronic anticoagulation, and those with malignancies to mitigate confounding. A meticulous 1:1 matching for significant comorbidities between cohorts was performed. Primary outcome studied is incidence of upper GI bleed, secondary outcomes include mortality, venous thromboembolism, length of stay. Results : Of the total IBD patients, 5,375 had cirrhosis. Following 1:1 matching, both the cirrhotic and non-cirrhotic groups comprised 4,195 patients. In the matched cohorts, IBD patients with cirrhosis exhibited an increased risk of upper gastrointestinal bleeding (RR-3.60, p < 0.0001) and mortality (RR-2.78, p < 0.002), while there was no significant difference in venous thromboembolism (VTE) events (RR-1.70, p-0.446). Length of stay did not significantly differ between the groups. Conclusion : This study uncovers a markedly elevated incidence of upper gastrointestinal bleeding among IBD patients with cirrhosis. Our results underscore the importance of diligent monitoring and close follow-up for individuals with both conditions. The efficacy of anticoagulation in preventing thromboembolic events remains uncertain in these patients, given the heightened propensity for bleeding observed in our study among those with IBD and cirrhosis. Future randomized clinical trials are warranted to investigate the effect of anticoagulation in this population, taking into account the varying severity of underlying cirrhosis. Cirrhosis coagulopathy Inflammatory bowel disease venous thromboembolism upper gastrointestinal bleeding Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Inflammatory bowel disease (IBD) represents a persistent inflammatory condition affecting the gastrointestinal tract, manifesting as Crohn's disease or ulcerative colitis. This condition arises in genetically predisposed individuals due to an amplified immune reaction to typically benign triggers like food and gut microbiota [1]. Being a pro-inflammatory condition, IBD increases the susceptibility to both arterial and venous thrombosis through analogous prothrombotic mechanisms. These mechanisms involve the activation of coagulation, partially mediated by the compromised intestinal barrier and the release of bacterial components [2]. In comparison to the general population, individuals with IBD face a threefold higher risk of venous thromboembolism (VTE) [3]. Previous studies have revealed that the presence of cirrhosis independently adversely affects outcomes in hospitalized IBD patients, manifesting as heightened in-hospital mortality and increased admission costs. Coagulopathy in cirrhosis is intricate due to the liver's role in clotting factor production [4]. Cirrhotic patients may transition to a procoagulant state in the presence of systemic inflammation, resulting in a higher risk of VTE compared to those without liver disease. There is paucity of data on VTE or hemorrhagic events in IBD patients with underlying cirrhosis [4,5]. The current guidelines regarding anticoagulation in IBD patients are based on international consensus statements (2021) and Canadian association of gastroenterology (2014) with weak levels of evidence which indicates a need for further studies [6,7]. They broadly suggest that thromboprophylaxis should be administered to IBD patients during hospitalization for “any cause”. This report also suggests that thromboprophylaxis does not elevate the risk of gastrointestinal bleeding in IBD patients with active disease (evidence level 2+) [7]. While these statements are supported by limited data, there is a notable absence of studies examining outcomes in IBD patients with underlying cirrhosis. Understanding the risk of VTE or gastrointestinal bleeding in these complex cases is crucial to improve outcomes and prevent harm. The cirrhotics with IBD may require closer monitoring including screening esophagogastroduodenoscopies (EGDs) to prevent adverse events from anticoagulation and hemodynamic fluctuations. Our study aims to address this gap in knowledge and contribute to a higher level of evidence, offering insights to refine consensus statements and guide management in patients with both cirrhosis and IBD. Methods We conducted a retrospective review of the Nationwide Inpatient Sample (NIS) database spanning from 2016 to 2020. The NIS is a comprehensive inpatient hospital database derived from hospitals' billing data, covering approximately 97% of the United States (US) population. It comprises a 20% stratified sample of participating hospitals across 48 states and includes patient and hospital-level discharge information. Each discharge is coded with one primary and multiple secondary diagnoses using the International Classification of Diseases, 9th and 10th Revision, Clinical Modification (ICD-10-CM) coding system. The NIS is part of the Healthcare Cost and Utilization Project under the Agency for Healthcare Research and Quality. We included patients with a primary diagnosis of inflammatory bowel disease (IBD) without active flare and examined baseline characteristics and outcomes in patients with and without underlying cirrhosis. Employing 1:1 matching, each patient with IBD and cirrhosis was matched against a patient with IBD without cirrhosis based on age, sex, ethnicity, and comorbidities, including coronary artery disease (CAD), diabetes mellitus (DM), hypertension (HTN), and chronic kidney disease (CKD). We excluded patients requiring chronic anticoagulation, such as those with a history of deep vein thrombosis (DVT) or pulmonary embolism (PE), mechanical heart valve, atrial fibrillation, and those predisposed to a procoagulant state like malignancy or pregnancy. The primary outcome studied was the incidence of upper GI bleed, with secondary outcomes including venous thromboembolism (VTE), mortality, and hospital length of stay. Statistical analyses were performed using linear and logistic regression models for continuous and categorical variables, respectively, to obtain standard errors, p-values, and 95% confidence intervals for each predictor variable. Results Baseline Characteristics and Comorbidities: We identified a total of 277,280 hospitalized patients with IBD between 2016 and 2020, among whom 5,375 had both IBD and cirrhosis. Patients with concurrent IBD and cirrhosis were older, with a mean age of 58 compared to 51 in those with IBD alone. After 1:1 matching, both groups were similar in gender, race, age, and comorbidities, including CAD, CKD, hypertension, and diabetes. In the unmatched cohorts, patients with IBD alone had a higher proportion of females (59% vs. 52%) and a racial distribution of Whites (75.9%), Blacks (11.6%), Hispanics (5.7%), Asian (1.1%), Native American (0.3%), and other (2.1%), similar to patients with IBD and cirrhosis. Baseline comorbidities were more prevalent in patients with cirrhosis, including type 2 DM (30.1% vs. 13.1%, p < 0.05), hypertension (35.6% vs. 27.5%, p < 0.05), CKD (22.8% vs. 12.4%, p < 0.05), and CAD (14% vs. 12%, p = 0.089). In the matched sample, racial distribution consisted of Whites (85.5%), Blacks (5.3%), Hispanics (6.4%), Asian (0.7%), Native American (0.3%), and other (1.5%), with similar comorbidity rates in each group (Table 1 ). In-Hospital Outcomes: Mortality: In both matched cohorts, inpatient mortality was higher in patients with IBD and cirrhosis compared to those without cirrhosis. The mortality rates were 3.2% vs. 0.7% (RR = 2.78, p < 0.05) (Table 2 ), (Fig. 1 ). Upper GI Bleeding: The risk of upper GI bleed, including variceal and nonvariceal bleed, was significantly higher in patients with IBD and cirrhosis compared to those without cirrhosis. The risk was 7.8% vs. 1.3% (RR = 3.6, p < 0.05) (Table 2 ), (Fig. 2 ). Venous Thromboembolism (VTE): The risk of VTE events in both matched and unmatched cohorts was noted to be discordant; however, neither showed statistical significance. The risk of VTE was slightly elevated in the IBD with cirrhosis group (also not statistically significant) (1.9% vs. 1.4%, RR = 1.7, p = 0.44) (Table 2 ), (Fig. 3 ). Hospital Length of Stay: The total length of stay was higher in the unmatched cohort among patients with IBD and cirrhosis compared to those without cirrhosis (6.07 days vs. 5.28, p < 0.05); however, after matching, this difference was no longer statistically significant (5.92 days vs. 5.26, p = 0.116) (Table 2 ), (Fig. 4 ). Table 1 Baseline characteristics BEFORE MATCHING AFTER MATCHING IBD without cirrhosis ((N = 271,905) IBD with cirrhosis (N = 5,375) P-value IBD without cirrhosis (N = 4,195) IBD with cirrhosis (N = 4,195) P-value Demographics Demographics Age (mean, std. dev.) 51.95, 46.11 58.12, 30.64 < .0001 Age group 1.00 19–32 205(4.8%) 205 33–46 680(16.2%) 680 47–59 1,425(33.9%) 1,425 60–72 1,490(35.5%) 1,490 over 73 395(9.4%) 395 Sex- M/F (%) 160,940 (59.1%) 2,800(52%) < .0001 Sex- M/F (%) 2,165(51.6%) 2,165 1.00 Ethnicity < .0001 Ethnicity 1.00 White (%) 206,530 (75.9%) 4,510(83.9%) White (%) 3,590(85.5%) 3,590 Black 31,735(11.6%) 375(6.9%) Black 225(5.3%) 225 Hispanic 15,640(5.7%) 310(5.7%) Hispanic 270(6.4%) 270 Asian PI 3,260(1.1%) 55(1.02%) Asian PI 30(0.7%) 30 Native American 860(0.3%) 35(0.6%) Native American 15(0.3%) 15 Other 5,805(2.1%) 115(2.1%) Other 66(1.5%) 66 Diagnoses(%) Diagnoses(%) CAD 32,545(11.9%) 755(14%) 0.0895 CAD 425(10.1%) 425 1.00 DM2 35,810(13.17%) 1,620(30.1%) < .0001 DM2 1,220(29.1%) 1,220 1.00 HTN 75,000(27.5%) 1,915(35.6%) < .0001 HTN 1,480(35.2%) 1,480 1.00 CKD 33,875 (12.4%) 1,230(22.8%) < .0001 CKD 870(20.7%) 870 1.00 Table 1 : Baseline Characteristics Before and After Matching: This table presents the baseline characteristics of patients with Inflammatory Bowel Disease (IBD) both before and after matching, with and without cirrhosis. The data are weighted to provide a representative sample. Demographics: Age (mean and standard deviation) and age group distribution, Sex distribution (% male and female), Ethnicity distribution (% White, Black, Hispanic, Asian Pacific Islander, Native American, Other) and Prevalence of comorbidities such as Coronary Artery Disease (CAD), Type 2 Diabetes Mellitus (DM2), Hypertension (HTN), and Chronic Kidney Disease (CKD). Abbreviations: IBD - Inflammatory Bowel Disease; CAD - Coronary Artery Disease; DM2 - Type 2 Diabetes Mellitus; HTN - Hypertension; CKD - Chronic Kidney Disease; std. dev. - standard deviation; PI - Pacific Islander. P-values indicate statistical significance levels, with values < 0.05 considered statistically significant.\" Table 2 Outcomes (data are weighted) MATCHED DATA IBD without cirrhosis (%) IBD with cirrhosis Relative risk with CI P- value VTE (Acute PE/DVT) 60 (1.4%) 80 (1.9%) 1.70 (0.760–1.80) 0.446 GI bleed 55 (1.3%) 330 (7.8%) 3.60 (2.08–6.27) < .0001 Mortality 30 (0.7%) 135 (3.2%) 2.78 (1.35–5.75) 0.002 Hospital LOS (mean, std. dev.) 5.26, 23.98 5.92, 12.970 n/a 0.1163 Table 2 : This table illustrates the outcomes associated with Inflammatory Bowel Disease (IBD) with and without cirrhosis with data presented as percentages. The data are weighted to ensure representativeness. The following outcomes are included: 1. VTE (Venous Thromboembolism), encompassing Acute Pulmonary Embolism (PE) and Deep Vein Thrombosis (DVT) 2. GI bleed (Gastrointestinal bleed) 3. Mortality rate 4. Hospital LOS (Length of Stay), represented by mean and standard deviation.For each outcome, the RR (Relative Risk) with confidence intervals (CI) and corresponding p-values are provided, indicating statistical significance levels. Discussion Inflammatory bowel disease (IBD) has been associated with an elevated risk of thrombosis, attributed to an upsurge in tissue factor, plasminogen activator inhibitor-1, and platelet count, along with a reduction in tissue plasminogen activator levels [8]. Additionally, mesenteric vein thrombosis and portal vein thrombosis have demonstrated higher prevalence in individuals with IBD compared to those without IBD [9]. This evidence underscores the imperative need for anticoagulant administration in IBD patients to mitigate the recurrence of thrombosis. Studies indicate that the timely initiation of thromboprophylaxis within 24 hours of admission reduces the likelihood of venous thromboembolism (VTE) by half [10]. Recognizing this, international consensus guidelines recommend administering thromboprophylaxis to hospitalized IBD patients for \"any cause\" [7]. However, the safety and benefits of thromboprophylaxis in IBD patients with cirrhosis remain uncertain, as systemic inflammation in cirrhosis, while promoting a procoagulant state, is also associated with an elevated risk of upper gastrointestinal (GI) bleeding [11]. Hence, the rationale for thromboprophylaxis in admitted IBD patients with cirrhosis warrants further investigation. In our study, the incidence of upper GI bleeding is significantly elevated in patients with both cirrhosis and IBD compared to those with IBD alone. In cirrhosis, the risk of upper GI hemorrhage from non-variceal causes, predominantly ulcers, contributes to 30–40% of cases, with varices accounting for the remainder [5]. In liver disease alone, upper GI bleeding is influenced by various interacting factors commonly encountered in decompensated cirrhosis. These factors encompass portal hypertension, endothelial dysfunction characterized by the hyperdynamic state, release of endogenous heparinoids especially during infection, renal failure leading to volume overload, vascular congestion, uremic platelet dysfunction, alterations in pro- and anticoagulant factors associated with cirrhosis, dysfibrinogenemia, changes in phospholipid metabolism, and thrombocytopenia [12]. The increased risk of upper GI bleeding in cirrhosis is not only due to higher portal hypertension causing variceal bleeding but also because cirrhotic patients are prone to non-variceal bleeding from ulcers due to coagulation disorders and thrombocytopenia. Despite similar frequencies of gastroduodenal ulcers compared to non-cirrhotic individuals, cirrhotic patients exhibit a higher presence of \"high-risk\" bleeding characteristics at the ulcer base (53% vs. 44%), necessitating more frequent endoscopic intervention (100% vs. 74%) [13]. Some studies also suggest that while patients with liver disease may encounter bleeding complications, a significant portion of these bleeds are not associated with hemostatic failure. Rather, they arise due to portal hypertension or mechanical vessel injury, which could occur due to accidental vessel puncture during invasive procedures [14]. Although IBD patients may occasionally report symptoms of upper GI hemorrhage, data indicate that there is no significant association between IBD and upper GI hemorrhage [15]. Consequently, cirrhosis emerges as a primary contributing factor to the heightened incidence of upper GI hemorrhage in IBD patients with cirrhosis in our study. Our investigation further reveals elevated mortality rates in patients with both cirrhosis and IBD compared to those with IBD alone. There is minimal data found on the impact of cirrhosis on the mortality of patients with IBD. However, when studied separately, the all-cause mortality for patients with IBD alone was 1.16 whereas the all-cause mortality rate was found to be six times higher in patients with compensated cirrhosis and about 10 times higher in those with decompensated cirrhosis in another study [16],[13]. The relative risk is higher in the matched sample, with a hazard ratio of approximately 3.0 in the matched controls, emphasizing the impact of cirrhosis on the mortality of IBD patients. In a recent study of notable indicators of mortality at the individual level, specific complications and accompanying conditions related to cirrhosis were. These included the clinical manifestation of bleeding, confirmed portal hypertension, hepatitis C infection, alcoholic liver disease, and the APR-DRG risk score, all of which demonstrated significance as predictors of mortality (all, P ≤ 0.005) [17]. As suggested by the existing literature and the results of our study, we propose that the mortality risk in IBD is exacerbated by the presence of cirrhosis of varying severity and accompanied by various complications. Notably, the incidence of VTE does not differ significantly between the two groups in our study. In cirrhosis alone, several suggested mechanisms indicate the overcoming of the anticoagulant effect, resulting in hypercoagulability: Thrombocytopenia, stemming from splenic sequestration and decreased TPO, is offset by increased vWF. Additionally, liver-derived procoagulant factors decrease, while concomitantly diminished anticoagulant factors possibly contribute to a hypercoagulable state [18]. Meanwhile, thromboembolism in IBD appears multifactorial, largely due to coagulation activation and platelet aggregation during systemic inflammation [19]. We hypothesize that deficiencies in coagulation factors and platelets may counterbalance the additive procoagulant effect of cirrhosis in patients with IBD. Furthermore, studies indicate that as cirrhosis progresses, there is incremental resistance to the native anticoagulation system, contributing to a relative hypercoagulable state [20]. Hence, further research is necessary to elucidate the role of various stages of cirrhosis in coagulopathy among patients with IBD [20]. Regarding the length of hospital stay, our study reveals no statistically significant difference between matched cohorts of IBD and IBD with cirrhosis. While the mean duration of hospitalization in US adults with chronic liver disease is reported to be 6.3 days, the median length of stay is 4 days in patients with IBD [11, 21]. Our findings suggest that the presence of cirrhosis does not significantly prolong the length of hospital stay in patients with IBD. Our study stands out as it explores novel territory, delving into the correlation between IBD and cirrhosis and its influence on patient outcomes, particularly regarding coagulopathy manifesting as GI bleeding. We aim to challenge the reliability of existing consensus guidelines regarding the use of anticoagulation in patients with IBD who also have underlying cirrhosis. By harnessing a comprehensive database like the NIS, we bolstered our study with a substantial sample size, thus augmenting its statistical power. Additionally, employing a 1:1 matching strategy enabled us to minimize bias in our observational study. Despite the novel insights and strengths of our study, several limitations must be acknowledged. Firstly, the retrospective nature of the study and reliance on the National Inpatient Sample (NIS) hinder our ability to establish causation between risk factors and outcomes. Additionally, the inability to stratify outcomes based on the stages of cirrhosis is a notable limitation, as this factor could substantially impact results. These limitations underscore the need for further prospective studies with more detailed data collection methods to better elucidate the relationships Declarations COI Statement: The authors of this manuscript do not have any conflicts of interest to disclose Author Contribution Medha Rajamanuri- Literature search, manuscript writingSreeram pannala- Data illustrationAnirudh Danduboyina- assisted with discussion writingSophia Dar- Assisted with manuscript editingSteve Scaife- Data analysisHafiz Muhammad Sharjeel Arshad- Manuscript editing References McDowell C, Farooq U, Haseeb M. Inflammatory Bowel Disease. [Updated 2023 Aug 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. 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Inflammatory Bowel Disease and Thrombosis: A National Inpatient Sample Study. TH Open. 2020;04(01):e51-58. Kaddourah O, Numan L, Jeepalyam S, Abughanimeh O, Ghanimeh MA, Abuamr K. Venous thromboembolism prophylaxis in inflammatory bowel disease flare-ups. Ann Gastroenterol [Internet]. 2019 Nov 15 [cited 2023 Dec 31];32(6):578-583. Available from: [https://pubmed.ncbi.nlm.nih.gov/31700234/](https://pubmed.ncbi.nlm.nih.gov/31700234/). Hirode G, Saab S, Wong RJ. Trends in the Burden of Chronic Liver Disease Among Hospitalized US Adults. JAMA Netw Open [Internet]. 2020 Apr 1 [cited 2024 Jan 1];3(4). Available from: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118516/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118516/). Caldwell S, Intagliata N. Dismantling the myth of \"autoanticoagulation\" in cirrhosis: An old dogma dies hard. 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All-cause hospitalizations for inflammatory bowel diseases: Can the reason for admission provide information on inpatient resource use? A study from a large veteran affairs hospital. Mil Med Res [Internet]. 2016 Sep 6 [cited 2024 Jan 1];3(1). Available from: /pmc/articles/PMC5011983/ Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-4266765\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":292947642,\"identity\":\"03588967-8784-4229-b468-c5c023648b60\",\"order_by\":0,\"name\":\"Medha Rajamanuri\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIiWNgGAWjYJACAwjF2P7zQwUDD4gpwcDATJSWBmmJM0RqgQMJ3jYoA58W3dmHHxT8zLHLM7h9uMFAcl6djMG1wwdvMFRYJzbg0GJ2Ls3AsHdbcrHBucSGhMJth3kMbqclWzCcScet5QyDgQHvNubEDWcYGw5IbjsA1JJjJsHYdhiPFvYPhn+31YO0NDbwzqkDasn/JsH4D58WHgNj3m2HQVqaGXgbmEG2sEkwNuDVUmAsu+144swzjG3MEscO80jeTjO2SDiWbozHYdsM326rTuw7w/6M8UNNnT3f7eSHNz7UWMvi0gIEbAaYYgm4lYMA8wP88qNgFIyCUTDiAQAFx1zPZYTgbwAAAABJRU5ErkJggg==\",\"orcid\":\"\",\"institution\":\"Southern Illinois University School of Medicine\",\"correspondingAuthor\":true,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Medha\",\"middleName\":\"\",\"lastName\":\"Rajamanuri\",\"suffix\":\"\"},{\"id\":292947643,\"identity\":\"dd02740d-4aee-4758-a224-1514b0e0fec5\",\"order_by\":1,\"name\":\"Sreeram Pannala\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Staten Island University Hospital\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Sreeram\",\"middleName\":\"\",\"lastName\":\"Pannala\",\"suffix\":\"\"},{\"id\":292947644,\"identity\":\"cccece24-0765-473a-ac85-36eda8488a38\",\"order_by\":2,\"name\":\"Sophia Dar\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Southern Illinois University School of Medicine\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Sophia\",\"middleName\":\"\",\"lastName\":\"Dar\",\"suffix\":\"\"},{\"id\":292947645,\"identity\":\"2f592f28-e835-45e4-8e4c-2d74e00dd14c\",\"order_by\":3,\"name\":\"Anirudh Danduboyina\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Gandhi Medical College\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Anirudh\",\"middleName\":\"\",\"lastName\":\"Danduboyina\",\"suffix\":\"\"},{\"id\":292947646,\"identity\":\"7d1d417b-5bc0-4c68-ac02-8103a337834a\",\"order_by\":4,\"name\":\"Steve scaife\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Southern Illinois University School of Medicine\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Steve\",\"middleName\":\"\",\"lastName\":\"scaife\",\"suffix\":\"\"},{\"id\":292947647,\"identity\":\"ceed62b6-ae0f-43dc-9f02-8e1fdd5539d1\",\"order_by\":5,\"name\":\"Hafiz Muhammad Sharjeel Arshad\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Southern Illinois University School of Medicine\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hafiz\",\"middleName\":\"Muhammad Sharjeel\",\"lastName\":\"Arshad\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2024-04-15 02:29:14\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-4266765/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-4266765/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":55117538,\"identity\":\"7000040d-ee3b-4ee8-9f70-8b7218eb8685\",\"added_by\":\"auto\",\"created_at\":\"2024-04-22 20:54:09\",\"extension\":\"jpeg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":107942,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eThis graph illustrates the proportions of mortality among patients diagnosed with Inflammatory Bowel Disease (IBD), both with and without cirrhosis, before and after propensity score matching. The graph reveals a higher proportion of mortality in the IBD cohort with cirrhosis compared to those without cirrhosis, underscoring the increased risk of mortality associated with cirrhosis in patients with IBD.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage1.jpeg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4266765/v1/de638b7637e93a50e3f5038c.jpeg\"},{\"id\":55117440,\"identity\":\"c85f1e1f-08c7-4bbc-9505-ac2084cef005\",\"added_by\":\"auto\",\"created_at\":\"2024-04-22 20:46:09\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":40215,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eThis graph illustrates the proportions of gastrointestinal (GI) bleeding events among patients diagnosed with Inflammatory Bowel Disease (IBD), both with and without cirrhosis, before and after propensity score matching. The graph highlights a higher proportion of GI bleeding events in the IBD cohort with cirrhosis compared to those without cirrhosis, indicating an increased risk of GI bleeding associated with cirrhosis in patients with IBD.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4266765/v1/b16c1d4d27cfcabdec4f333a.png\"},{\"id\":55117437,\"identity\":\"1005c223-8d99-4878-a770-c605b3675c8d\",\"added_by\":\"auto\",\"created_at\":\"2024-04-22 20:46:09\",\"extension\":\"jpeg\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":126090,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eThis graph illustrates the proportions of Venous Thromboembolism (VTE) events, encompassing Acute Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE), among patients diagnosed with Inflammatory Bowel Disease (IBD), both with and without cirrhosis, before and after propensity score matching. The graph depicts a higher proportion of VTE events in the unmatched IBD cohort with cirrhosis compared to those without cirrhosis, highlighting the elevated risk of VTE associated with cirrhosis in patients with IBD, however, this association was not found in the matched cohort.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage3.jpeg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4266765/v1/9115e96cef7e09bda4a57948.jpeg\"},{\"id\":55117715,\"identity\":\"a5da5f99-6e3c-4c45-9cd3-99b5a1e87674\",\"added_by\":\"auto\",\"created_at\":\"2024-04-22 21:02:09\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":35418,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eThis graph illustrates the mean length of stay in days for patients diagnosed with Inflammatory Bowel Disease (IBD), both with and without cirrhosis, before and after propensity score matching. The graph demonstrates a higher mean length of stay in the IBD cohort with cirrhosis compared to those without cirrhosis, indicating the impact of cirrhosis on hospitalization duration.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage4.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4266765/v1/d042ce2a1b49062b4f5aa5ad.png\"},{\"id\":55599144,\"identity\":\"d95232b9-b30d-47f2-9d1f-5fab857d0f04\",\"added_by\":\"auto\",\"created_at\":\"2024-04-30 11:19:14\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":591187,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4266765/v1/83f4d646-4f3e-4dff-b246-c489aecda91c.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"The Risk of Upper Gastrointestinal Bleeding and Coagulopathy in IBD Patients with Cirrhosis\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eInflammatory bowel disease (IBD) represents a persistent inflammatory condition affecting the gastrointestinal tract, manifesting as Crohn's disease or ulcerative colitis. This condition arises in genetically predisposed individuals due to an amplified immune reaction to typically benign triggers like food and gut microbiota [1]. Being a pro-inflammatory condition, IBD increases the susceptibility to both arterial and venous thrombosis through analogous prothrombotic mechanisms. These mechanisms involve the activation of coagulation, partially mediated by the compromised intestinal barrier and the release of bacterial components [2]. In comparison to the general population, individuals with IBD face a threefold higher risk of venous thromboembolism (VTE) [3]. Previous studies have revealed that the presence of cirrhosis independently adversely affects outcomes in hospitalized IBD patients, manifesting as heightened in-hospital mortality and increased admission costs. Coagulopathy in cirrhosis is intricate due to the liver's role in clotting factor production [4]. Cirrhotic patients may transition to a procoagulant state in the presence of systemic inflammation, resulting in a higher risk of VTE compared to those without liver disease. There is paucity of data on VTE or hemorrhagic events in IBD patients with underlying cirrhosis [4,5]. The current guidelines regarding anticoagulation in IBD patients are based on international consensus statements (2021) and Canadian association of gastroenterology (2014) with weak levels of evidence which indicates a need for further studies [6,7]. They broadly suggest that thromboprophylaxis should be administered to IBD patients during hospitalization for \\u0026ldquo;any cause\\u0026rdquo;. This report also suggests that thromboprophylaxis does not elevate the risk of gastrointestinal bleeding in IBD patients with active disease (evidence level 2+) [7]. While these statements are supported by limited data, there is a notable absence of studies examining outcomes in IBD patients with underlying cirrhosis. Understanding the risk of VTE or gastrointestinal bleeding in these complex cases is crucial to improve outcomes and prevent harm. The cirrhotics with IBD may require closer monitoring including screening esophagogastroduodenoscopies (EGDs) to prevent adverse events from anticoagulation and hemodynamic fluctuations. Our study aims to address this gap in knowledge and contribute to a higher level of evidence, offering insights to refine consensus statements and guide management in patients with both cirrhosis and IBD.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003e We conducted a retrospective review of the Nationwide Inpatient Sample (NIS) database spanning from 2016 to 2020. The NIS is a comprehensive inpatient hospital database derived from hospitals' billing data, covering approximately 97% of the United States (US) population. It comprises a 20% stratified sample of participating hospitals across 48 states and includes patient and hospital-level discharge information. Each discharge is coded with one primary and multiple secondary diagnoses using the International Classification of Diseases, 9th and 10th Revision, Clinical Modification (ICD-10-CM) coding system. The NIS is part of the Healthcare Cost and Utilization Project under the Agency for Healthcare Research and Quality.\\u003c/p\\u003e \\u003cp\\u003eWe included patients with a primary diagnosis of inflammatory bowel disease (IBD) without active flare and examined baseline characteristics and outcomes in patients with and without underlying cirrhosis. Employing 1:1 matching, each patient with IBD and cirrhosis was matched against a patient with IBD without cirrhosis based on age, sex, ethnicity, and comorbidities, including coronary artery disease (CAD), diabetes mellitus (DM), hypertension (HTN), and chronic kidney disease (CKD). We excluded patients requiring chronic anticoagulation, such as those with a history of deep vein thrombosis (DVT) or pulmonary embolism (PE), mechanical heart valve, atrial fibrillation, and those predisposed to a procoagulant state like malignancy or pregnancy. The primary outcome studied was the incidence of upper GI bleed, with secondary outcomes including venous thromboembolism (VTE), mortality, and hospital length of stay. Statistical analyses were performed using linear and logistic regression models for continuous and categorical variables, respectively, to obtain standard errors, p-values, and 95% confidence intervals for each predictor variable.\\u003c/p\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eBaseline Characteristics and Comorbidities:\\u003c/h2\\u003e \\u003cp\\u003eWe identified a total of 277,280 hospitalized patients with IBD between 2016 and 2020, among whom 5,375 had both IBD and cirrhosis. Patients with concurrent IBD and cirrhosis were older, with a mean age of 58 compared to 51 in those with IBD alone. After 1:1 matching, both groups were similar in gender, race, age, and comorbidities, including CAD, CKD, hypertension, and diabetes. In the unmatched cohorts, patients with IBD alone had a higher proportion of females (59% vs. 52%) and a racial distribution of Whites (75.9%), Blacks (11.6%), Hispanics (5.7%), Asian (1.1%), Native American (0.3%), and other (2.1%), similar to patients with IBD and cirrhosis. Baseline comorbidities were more prevalent in patients with cirrhosis, including type 2 DM (30.1% vs. 13.1%, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05), hypertension (35.6% vs. 27.5%, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05), CKD (22.8% vs. 12.4%, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05), and CAD (14% vs. 12%, p\\u0026thinsp;=\\u0026thinsp;0.089). In the matched sample, racial distribution consisted of Whites (85.5%), Blacks (5.3%), Hispanics (6.4%), Asian (0.7%), Native American (0.3%), and other (1.5%), with similar comorbidity rates in each group (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eIn-Hospital Outcomes:\\u003c/h2\\u003e \\u003cp\\u003eMortality: In both matched cohorts, inpatient mortality was higher in patients with IBD and cirrhosis compared to those without cirrhosis. The mortality rates were 3.2% vs. 0.7% (RR\\u0026thinsp;=\\u0026thinsp;2.78, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05) (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e), (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eUpper GI Bleeding: The risk of upper GI bleed, including variceal and nonvariceal bleed, was significantly higher in patients with IBD and cirrhosis compared to those without cirrhosis. The risk was 7.8% vs. 1.3% (RR\\u0026thinsp;=\\u0026thinsp;3.6, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05) (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e), (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eVenous Thromboembolism (VTE): The risk of VTE events in both matched and unmatched cohorts was noted to be discordant; however, neither showed statistical significance. The risk of VTE was slightly elevated in the IBD with cirrhosis group (also not statistically significant) (1.9% vs. 1.4%, RR\\u0026thinsp;=\\u0026thinsp;1.7, p\\u0026thinsp;=\\u0026thinsp;0.44) (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e), (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eHospital Length of Stay: The total length of stay was higher in the unmatched cohort among patients with IBD and cirrhosis compared to those without cirrhosis (6.07 days vs. 5.28, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05); however, after matching, this difference was no longer statistically significant (5.92 days vs. 5.26, p\\u0026thinsp;=\\u0026thinsp;0.116) (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e), (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e).\\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 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eBaseline characteristics\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"8\\\"\\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 \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c7\\\" colnum=\\\"7\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c8\\\" colnum=\\\"8\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"3\\\" nameend=\\\"c4\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003eBEFORE MATCHING\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"3\\\" nameend=\\\"c8\\\" namest=\\\"c6\\\"\\u003e \\u003cp\\u003eAFTER MATCHING\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eIBD without cirrhosis ((N\\u0026thinsp;=\\u0026thinsp;271,905)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eIBD with cirrhosis (N\\u0026thinsp;=\\u0026thinsp;5,375)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eP-value\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eIBD without cirrhosis (N\\u0026thinsp;=\\u0026thinsp;4,195)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003eIBD with cirrhosis (N\\u0026thinsp;=\\u0026thinsp;4,195)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003eP-value\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eDemographics\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eDemographics\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eAge (mean, std. dev.)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e51.95, 46.11\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e58.12, 30.64\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u0026lt;\\u0026thinsp;.0001\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eAge group\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e19\\u0026ndash;32\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e205(4.8%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e205\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e33\\u0026ndash;46\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e680(16.2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e680\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e47\\u0026ndash;59\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1,425(33.9%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1,425\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e60\\u0026ndash;72\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1,490(35.5%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1,490\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eover 73\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e395(9.4%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e395\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eSex- M/F (%)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e160,940 (59.1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2,800(52%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u0026lt;\\u0026thinsp;.0001\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eSex- M/F (%)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e2,165(51.6%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e2,165\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eEthnicity\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u0026lt;\\u0026thinsp;.0001\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eEthnicity\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eWhite (%)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e206,530 (75.9%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e4,510(83.9%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eWhite (%)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e3,590(85.5%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e3,590\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eBlack\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e31,735(11.6%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e375(6.9%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eBlack\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e225(5.3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e225\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eHispanic\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e15,640(5.7%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e310(5.7%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eHispanic\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e270(6.4%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e270\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eAsian PI\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e3,260(1.1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e55(1.02%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eAsian PI\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e30(0.7%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e30\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eNative American\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e860(0.3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e35(0.6%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eNative American\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e15(0.3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e15\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eOther\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e5,805(2.1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e115(2.1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eOther\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e66(1.5%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e66\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eDiagnoses(%)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eDiagnoses(%)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eCAD\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e32,545(11.9%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e755(14%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.0895\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eCAD\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e425(10.1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e425\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eDM2\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e35,810(13.17%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1,620(30.1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u0026lt;\\u0026thinsp;.0001\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eDM2\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1,220(29.1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1,220\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eHTN\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e75,000(27.5%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1,915(35.6%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u0026lt;\\u0026thinsp;.0001\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eHTN\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1,480(35.2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1,480\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eCKD\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e33,875 (12.4%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1,230(22.8%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u0026lt;\\u0026thinsp;.0001\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eCKD\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e870(20.7%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e870\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e \\u003cp\\u003e1.00\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eTable\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e: Baseline Characteristics Before and After Matching: This table presents the baseline characteristics of patients with Inflammatory Bowel Disease (IBD) both before and after matching, with and without cirrhosis. The data are weighted to provide a representative sample. Demographics: Age (mean and standard deviation) and age group distribution, Sex distribution (% male and female), Ethnicity distribution (% White, Black, Hispanic, Asian Pacific Islander, Native American, Other) and Prevalence of comorbidities such as Coronary Artery Disease (CAD), Type 2 Diabetes Mellitus (DM2), Hypertension (HTN), and Chronic Kidney Disease (CKD). Abbreviations: IBD - Inflammatory Bowel Disease; CAD - Coronary Artery Disease; DM2 - Type 2 Diabetes Mellitus; HTN - Hypertension; CKD - Chronic Kidney Disease; std. dev. - standard deviation; PI - Pacific Islander. P-values indicate statistical significance levels, with values\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 considered statistically significant.\\\"\\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\\u003eOutcomes (data are weighted)\\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\\\" colspan=\\\"5\\\" nameend=\\\"c5\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003eMATCHED DATA\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eIBD without cirrhosis (%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eIBD with cirrhosis\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eRelative risk with CI\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eP- value\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eVTE (Acute PE/DVT)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e60 (1.4%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e80 (1.9%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.70 (0.760\\u0026ndash;1.80)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.446\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eGI bleed\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e55 (1.3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e330 (7.8%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e3.60 (2.08\\u0026ndash;6.27)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u0026lt;\\u0026thinsp;.0001\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eMortality\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e30 (0.7%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e135 (3.2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e2.78 (1.35\\u0026ndash;5.75)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.002\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eHospital LOS (mean, std. dev.)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e5.26, 23.98\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e5.92, 12.970\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003en/a\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.1163\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eTable\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e: This table illustrates the outcomes associated with Inflammatory Bowel Disease (IBD) with and without cirrhosis with data presented as percentages. The data are weighted to ensure representativeness. The following outcomes are included: 1. VTE (Venous Thromboembolism), encompassing Acute Pulmonary Embolism (PE) and Deep Vein Thrombosis (DVT) 2. GI bleed (Gastrointestinal bleed) 3. Mortality rate 4. Hospital LOS (Length of Stay), represented by mean and standard deviation.For each outcome, the RR (Relative Risk) with confidence intervals (CI) and corresponding p-values are provided, indicating statistical significance levels.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eInflammatory bowel disease (IBD) has been associated with an elevated risk of thrombosis, attributed to an upsurge in tissue factor, plasminogen activator inhibitor-1, and platelet count, along with a reduction in tissue plasminogen activator levels [8]. Additionally, mesenteric vein thrombosis and portal vein thrombosis have demonstrated higher prevalence in individuals with IBD compared to those without IBD [9]. This evidence underscores the imperative need for anticoagulant administration in IBD patients to mitigate the recurrence of thrombosis. Studies indicate that the timely initiation of thromboprophylaxis within 24 hours of admission reduces the likelihood of venous thromboembolism (VTE) by half [10]. Recognizing this, international consensus guidelines recommend administering thromboprophylaxis to hospitalized IBD patients for \\\"any cause\\\" [7]. However, the safety and benefits of thromboprophylaxis in IBD patients with cirrhosis remain uncertain, as systemic inflammation in cirrhosis, while promoting a procoagulant state, is also associated with an elevated risk of upper gastrointestinal (GI) bleeding [11]. Hence, the rationale for thromboprophylaxis in admitted IBD patients with cirrhosis warrants further investigation.\\u003c/p\\u003e \\u003cp\\u003eIn our study, the incidence of upper GI bleeding is significantly elevated in patients with both cirrhosis and IBD compared to those with IBD alone. In cirrhosis, the risk of upper GI hemorrhage from non-variceal causes, predominantly ulcers, contributes to 30\\u0026ndash;40% of cases, with varices accounting for the remainder [5].\\u003c/p\\u003e \\u003cp\\u003eIn liver disease alone, upper GI bleeding is influenced by various interacting factors commonly encountered in decompensated cirrhosis. These factors encompass portal hypertension, endothelial dysfunction characterized by the hyperdynamic state, release of endogenous heparinoids especially during infection, renal failure leading to volume overload, vascular congestion, uremic platelet dysfunction, alterations in pro- and anticoagulant factors associated with cirrhosis, dysfibrinogenemia, changes in phospholipid metabolism, and thrombocytopenia [12]. The increased risk of upper GI bleeding in cirrhosis is not only due to higher portal hypertension causing variceal bleeding but also because cirrhotic patients are prone to non-variceal bleeding from ulcers due to coagulation disorders and thrombocytopenia. Despite similar frequencies of gastroduodenal ulcers compared to non-cirrhotic individuals, cirrhotic patients exhibit a higher presence of \\\"high-risk\\\" bleeding characteristics at the ulcer base (53% vs. 44%), necessitating more frequent endoscopic intervention (100% vs. 74%) [13]. Some studies also suggest that while patients with liver disease may encounter bleeding complications, a significant portion of these bleeds are not associated with hemostatic failure. Rather, they arise due to portal hypertension or mechanical vessel injury, which could occur due to accidental vessel puncture during invasive procedures [14].\\u003c/p\\u003e \\u003cp\\u003eAlthough IBD patients may occasionally report symptoms of upper GI hemorrhage, data indicate that there is no significant association between IBD and upper GI hemorrhage [15]. Consequently, cirrhosis emerges as a primary contributing factor to the heightened incidence of upper GI hemorrhage in IBD patients with cirrhosis in our study.\\u003c/p\\u003e \\u003cp\\u003eOur investigation further reveals elevated mortality rates in patients with both cirrhosis and IBD compared to those with IBD alone. There is minimal data found on the impact of cirrhosis on the mortality of patients with IBD. However, when studied separately, the all-cause mortality for patients with IBD alone was 1.16 whereas the all-cause mortality rate was found to be six times higher in patients with compensated cirrhosis and about 10 times higher in those with decompensated cirrhosis in another study [16],[13]. The relative risk is higher in the matched sample, with a hazard ratio of approximately 3.0 in the matched controls, emphasizing the impact of cirrhosis on the mortality of IBD patients. In a recent study of notable indicators of mortality at the individual level, specific complications and accompanying conditions related to cirrhosis were. These included the clinical manifestation of bleeding, confirmed portal hypertension, hepatitis C infection, alcoholic liver disease, and the APR-DRG risk score, all of which demonstrated significance as predictors of mortality (all, P\\u0026thinsp;\\u0026le;\\u0026thinsp;0.005) [17]. As suggested by the existing literature and the results of our study, we propose that the mortality risk in IBD is exacerbated by the presence of cirrhosis of varying severity and accompanied by various complications.\\u003c/p\\u003e \\u003cp\\u003eNotably, the incidence of VTE does not differ significantly between the two groups in our study. In cirrhosis alone, several suggested mechanisms indicate the overcoming of the anticoagulant effect, resulting in hypercoagulability: Thrombocytopenia, stemming from splenic sequestration and decreased TPO, is offset by increased vWF. Additionally, liver-derived procoagulant factors decrease, while concomitantly diminished anticoagulant factors possibly contribute to a hypercoagulable state [18]. Meanwhile, thromboembolism in IBD appears multifactorial, largely due to coagulation activation and platelet aggregation during systemic inflammation [19]. We hypothesize that deficiencies in coagulation factors and platelets may counterbalance the additive procoagulant effect of cirrhosis in patients with IBD. Furthermore, studies indicate that as cirrhosis progresses, there is incremental resistance to the native anticoagulation system, contributing to a relative hypercoagulable state [20]. Hence, further research is necessary to elucidate the role of various stages of cirrhosis in coagulopathy among patients with IBD [20].\\u003c/p\\u003e \\u003cp\\u003eRegarding the length of hospital stay, our study reveals no statistically significant difference between matched cohorts of IBD and IBD with cirrhosis. While the mean duration of hospitalization in US adults with chronic liver disease is reported to be 6.3 days, the median length of stay is 4 days in patients with IBD [11, 21]. Our findings suggest that the presence of cirrhosis does not significantly prolong the length of hospital stay in patients with IBD.\\u003c/p\\u003e \\u003cp\\u003eOur study stands out as it explores novel territory, delving into the correlation between IBD and cirrhosis and its influence on patient outcomes, particularly regarding coagulopathy manifesting as GI bleeding. We aim to challenge the reliability of existing consensus guidelines regarding the use of anticoagulation in patients with IBD who also have underlying cirrhosis. By harnessing a comprehensive database like the NIS, we bolstered our study with a substantial sample size, thus augmenting its statistical power. Additionally, employing a 1:1 matching strategy enabled us to minimize bias in our observational study.\\u003c/p\\u003e \\u003cp\\u003eDespite the novel insights and strengths of our study, several limitations must be acknowledged. Firstly, the retrospective nature of the study and reliance on the National Inpatient Sample (NIS) hinder our ability to establish causation between risk factors and outcomes. Additionally, the inability to stratify outcomes based on the stages of cirrhosis is a notable limitation, as this factor could substantially impact results. These limitations underscore the need for further prospective studies with more detailed data collection methods to better elucidate the relationships\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003ch2\\u003eCOI Statement: \\u003c/h2\\u003e\\n\\u003cp\\u003eThe authors of this manuscript do not have any conflicts of interest to disclose\\u003c/p\\u003e\\n\\u003ch2\\u003eAuthor Contribution\\u003c/h2\\u003e\\u003cp\\u003eMedha Rajamanuri- Literature search, manuscript writingSreeram pannala- Data illustrationAnirudh Danduboyina- assisted with discussion writingSophia Dar- Assisted with manuscript editingSteve Scaife- Data analysisHafiz Muhammad Sharjeel Arshad- Manuscript editing\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eMcDowell C, Farooq U, Haseeb M. Inflammatory Bowel Disease. [Updated 2023 Aug 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: [https://www.ncbi.nlm.nih.gov/books/NBK470312/](https://www.ncbi.nlm.nih.gov/books/NBK470312/)\\u003c/li\\u003e\\n\\u003cli\\u003eStadnicki A, Stadnicka I. Venous and arterial thromboembolism in patients with inflammatory bowel diseases. World J Gastroenterol. 2021;27(40):6757-6774. doi:10.3748/wjg.v27.i40.6757. PMID: 34790006.\\u003c/li\\u003e\\n\\u003cli\\u003eNguyen GC, Bernstein CN, Bitton A, et al. Consensus statements on the risk, prevention, and treatment of venous thromboembolism in inflammatory bowel disease: Canadian Association of Gastroenterology. Gastroenterology. 2014;146(3):835-848.e6. doi:10.1053/j.gastro.2014.01.042\\u003c/li\\u003e\\n\\u003cli\\u003eTaneja V, Stein DJ, Feuerstein JD. Impact of Cirrhosis on Outcomes in Inflammatory Bowel Disease Hospitalizations. J Clin Gastroenterol. 2022 Sep 1;56(8):718-723. doi:10.1097/MCG.0000000000001640. Epub 2022 Feb 14. PMID: 35152240.\\u003c/li\\u003e\\n\\u003cli\\u003eSingh AD, Mucha SR, Lindenmeyer CC. Cleveland Clinic Journal of Medicine. 2022 Sep;89(9):523-533. doi:10.3949/ccjm.89a.21018\\u003c/li\\u003e\\n\\u003cli\\u003eD\\u0026apos;Ardes D, Boccatonda A, Cocco G, Fabiani S, Rossi I, Bucci M, Guagnano MT, Schiavone C, Cipollone F. Impaired coagulation, liver dysfunction and COVID-19: Discovering an intriguing relationship. World J Gastroenterol. 2022 Mar 21;28(11):1102-1112. doi:10.3748/wjg.v28.i11.1102. PMID: 35431501; PMCID: PMC8985482.\\u003c/li\\u003e\\n\\u003cli\\u003eOlivera PA, Zuily S, Kotze PG, et al. International consensus on the prevention of venous and arterial thrombotic events in patients with inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2021;18(12):857-873. doi:10.1038/s41575-021-00492-8.\\u003c/li\\u003e\\n\\u003cli\\u003eSenchenkova E, Seifert H, Granger DN. Hypercoagulability and Platelet Abnormalities in Inflammatory Bowel Disease. Semin Thromb Hemost [Internet]. 2015 Aug 13 [cited 2023 Dec 31];41(6):582-589. Available from: [https://pubmed.ncbi.nlm.nih.gov/26270113/](https://pubmed.ncbi.nlm.nih.gov/26270113/).\\u003c/li\\u003e\\n\\u003cli\\u003eCohen JB, Comer DM, Yabes JG, Ragni M V. Inflammatory Bowel Disease and Thrombosis: A National Inpatient Sample Study. TH Open. 2020;04(01):e51-58.\\u003c/li\\u003e\\n\\u003cli\\u003eKaddourah O, Numan L, Jeepalyam S, Abughanimeh O, Ghanimeh MA, Abuamr K. Venous thromboembolism prophylaxis in inflammatory bowel disease flare-ups. Ann Gastroenterol [Internet]. 2019 Nov 15 [cited 2023 Dec 31];32(6):578-583. Available from: [https://pubmed.ncbi.nlm.nih.gov/31700234/](https://pubmed.ncbi.nlm.nih.gov/31700234/).\\u003c/li\\u003e\\n\\u003cli\\u003eHirode G, Saab S, Wong RJ. Trends in the Burden of Chronic Liver Disease Among Hospitalized US Adults. JAMA Netw Open [Internet]. 2020 Apr 1 [cited 2024 Jan 1];3(4). Available from: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118516/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118516/).\\u003c/li\\u003e\\n\\u003cli\\u003eCaldwell S, Intagliata N. Dismantling the myth of \\u0026quot;autoanticoagulation\\u0026quot; in cirrhosis: An old dogma dies hard. Hepatology. 2012; [First published: April 19, 2012]. doi:10.1002/hep.25623\\u003c/li\\u003e\\n\\u003cli\\u003eGonz\\u0026aacute;lez-Gonz\\u0026aacute;lez JA, Garc\\u0026iacute;a-Compean D, V\\u0026aacute;zquez-Elizondo G, Garza-Galindo A, J\\u0026aacute;quez-Quintana JO, Maldonado-Garza H. Nonvariceal upper gastrointestinal bleeding in patients with liver cirrhosis: Clinical features, outcomes and predictors of in-hospital mortality. A prospective study. Ann Hepatol. 2011;10(3):287-295.\\u003c/li\\u003e\\n\\u003cli\\u003eVilla E, Bianchini M, Blasi A, Denys A, Giannini EG, de Gottardi A, Lisman T, de Raucourt E, Ripoll C, Rautou PE. EASL Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis. J Hepatol. 2022;76(5):1151-1184. doi:10.1016/j.jhep.2021.09.003\\u003c/li\\u003e\\n\\u003cli\\u003eLi, Fangyu, et al. \\u0026ldquo;The Association between Inflammatory Bowel Disease and All-Cause and Cause-Specific Mortality in the UK Biobank.\\u0026rdquo; Annals of Epidemiology, Elsevier BV, Dec. 2023, pp. 15\\u0026ndash;22. Crossref, doi:10.1016/j.annepidem.2023.10.008.\\u003c/li\\u003e\\n\\u003cli\\u003eFleming KM, Aithal GP, Card TR, West J. All-cause mortality in people with cirrhosis compared with the general population: A population-based cohort study. Liver Int. 2012;32(1):79\\u0026ndash;84. \\u003c/li\\u003e\\n\\u003cli\\u003eMathur AK, Chakrabarti AK, Mellinger JL, et al. Hospital resource intensity and cirrhosis mortality in United States. World J Gastroenterol. 2017;23(10):1857-1865. doi:10.3748/wjg.v23.i10.1857\\u003c/li\\u003e\\n\\u003cli\\u003eO\\u0026apos;Leary JG, Greenberg CS, Patton HM, Caldwell SH. AGA Clinical Practice Update: Coagulation in Cirrhosis. Gastroenterology. 2019;157(1):34-43.e1. doi:10.1053/j.gastro.2019.03.070\\u003c/li\\u003e\\n\\u003cli\\u003eStadnicki A. Involvement of Coagulation and Hemostasis in Inflammatory Bowel Diseases. Curr Vasc Pharmacol. 2012;10(5):585-590. doi:10.2174/157016112801784495\\u003c/li\\u003e\\n\\u003cli\\u003eTripodi A, Primignani M, Chantarangkul V, et al. The endogenous thrombin potential and thromboembolic risk in patients with cirrhosis: a prospective study. Hepatology. 2011;53(2):446-455. doi:10.1002/hep.25623\\u003c/li\\u003e\\n\\u003cli\\u003eMalhotra A, Mandip KC, Shaukat A, Rector T. All-cause hospitalizations for inflammatory bowel diseases: Can the reason for admission provide information on inpatient resource use? A study from a large veteran affairs hospital. Mil Med Res [Internet]. 2016 Sep 6 [cited 2024 Jan 1];3(1). Available from: /pmc/articles/PMC5011983/\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Cirrhosis, coagulopathy, Inflammatory bowel disease, venous thromboembolism, upper gastrointestinal bleeding\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-4266765/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-4266765/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eIntroduction\\u003c/strong\\u003e: In cirrhotic patients, systemic inflammation disrupts the delicate balance of hemostatic variables, akin to what occurs in inflammatory bowel disease (IBD), potentially resulting in a shift towards either a procoagulant or anticoagulant state. Current guidelines advocating for anticoagulation use in hospitalized IBD patients lack strong evidence, and there is a notable absence of guidelines tailored specifically for those with underlying cirrhosis. This study seeks to explore how underlying cirrhosis impacts the risk of coagulopathy and gastrointestinal bleeding in IBD patients, aiming to provide insights for making well-informed decisions regarding anticoagulation therapy.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003ePatients and Methods\\u003c/strong\\u003e: Utilizing the National Inpatient Sample database, we identified hospitalizations with a primary or secondary diagnosis of IBD and cirrhosis based on ICD-10 codes from 2016 to 2020. This retrospective cohort study excluded pregnant women, patients requiring chronic anticoagulation, and those with malignancies to mitigate confounding. A meticulous 1:1 matching for significant comorbidities between cohorts was performed. Primary outcome studied is incidence of upper GI bleed, secondary outcomes include mortality, venous thromboembolism, length of stay.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults\\u003c/strong\\u003e: Of the total IBD patients, 5,375 had cirrhosis. Following 1:1 matching, both the cirrhotic and non-cirrhotic groups comprised 4,195 patients. In the matched cohorts, IBD patients with cirrhosis exhibited an increased risk of upper gastrointestinal bleeding (RR-3.60, p \\u0026lt; 0.0001) and mortality (RR-2.78, p \\u0026lt; 0.002), while there was no significant difference in venous thromboembolism (VTE) events (RR-1.70, p-0.446). Length of stay did not significantly differ between the groups.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion\\u003c/strong\\u003e: This study uncovers a markedly elevated incidence of upper gastrointestinal bleeding among IBD patients with cirrhosis. Our results underscore the importance of diligent monitoring and close follow-up for individuals with both conditions. The efficacy of anticoagulation in preventing thromboembolic events remains uncertain in these patients, given the heightened propensity for bleeding observed in our study among those with IBD and cirrhosis. Future randomized clinical trials are warranted to investigate the effect of anticoagulation in this population, taking into account the varying severity of underlying cirrhosis.\\u003c/p\\u003e\",\"manuscriptTitle\":\"The Risk of Upper Gastrointestinal Bleeding and Coagulopathy in IBD Patients with Cirrhosis\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-04-22 20:46:04\",\"doi\":\"10.21203/rs.3.rs-4266765/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"15d12211-fffe-45ba-894f-6e7a324243ba\",\"owner\":[],\"postedDate\":\"April 22nd, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-04-30T11:11:01+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-04-22 20:46:04\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-4266765\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-4266765\",\"identity\":\"rs-4266765\",\"version\":[\"v1\"]},\"buildId\":\"zQwnuV7TCBrMSSSToR1PI\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}