Venous Thromboembolism and Bleeding Risk in a Population with Obesity Hospitalized for Surgery and Receiving Enoxaparin for Thromboprophylaxis

Venous Thromboembolism and Bleeding Risk in a Population with Obesity Hospitalized for Surgery and Receiving Enoxaparin for Thromboprophylaxis | 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 Research Article Venous Thromboembolism and Bleeding Risk in a Population with Obesity Hospitalized for Surgery and Receiving Enoxaparin for Thromboprophylaxis Walter Ageno, Marc Carrier, Christine Stroh, Yasmina Djoudi, Mohamed Abdel-Moneim, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7274037/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Introduction: Obese patients hospitalized for surgery are at high risk of venous thromboembolism (VTE). The optimal dose and duration of thromboprophylaxis with low molecular weight heparin for these patients are uncertain. Aims To assess the time-course, rates and risk factors for VTE and major bleeding (MB) in a population of surgical patients with obesity receiving pharmacological thromboprophylaxis with enoxaparin. Methods Patients with body mass index (BMI) > 30 kg/m 2 hospitalized with surgeries between 2010 and 2019 who received thromboprophylaxis with enoxaparin were selected from the US Optum database. Exclusion criteria were VTE, MB, or surgery in previous 90-days, and ongoing anticoagulant treatment or dual antiplatelet therapy. VTE and MB event rates over a 90-day follow-up post enoxaparin initiation were estimated via the Kaplan-Meier (KM) method. Risk factors associated with outcome events were identified via Cox proportional hazard models. Results A total of 30,492 patients met selection criteria (median age 55, IQR 48–66), 12,058 patients received the standard dose, with 18,300 receiving higher doses. KM event rates at 90-days for VTE and MB were 2.5% and 1.2%, respectively. The highest VTE rates were observed in patients hospitalized for thoracic surgery (4.9%). History of VTE was the strongest predictor of post-surgery VTE (HR 5.58, 95% CI 4.69–6.63) while history of MB was the strongest predictor of post-surgery bleeding (HR 2.71, 95% CI 1.34–5.48). Conclusions The rates of VTE are non-negligible in surgical patients with obesity receiving thromboprophylaxis with enoxaparin. Individual risk stratification is warranted to identify optimal doses/duration of pharmacologic thromboprophylaxis. Figures Figure 1 Figure 2 Key Points • Patients with obesity hospitalized for surgery are at high risk of VTE and MB. • VTE rates estimated using claims data in this population were non-negligible. • History of VTE and thoracic surgery were associated with a higher risk for VTE 90 days post discharge. • Individual risk stratification is warranted to identify optimal dosage/duration. Introduction In 2024, it was estimated that more than one billion individuals (880 million adults and 159 million children) worldwide have obesity. [ 1 ] Obesity, defined as body mass index (BMI) ≥ 30 kg/m 2 , is a global epidemic linked to increased morbidity and mortality. It is also an independent risk factor for developing venous thromboembolic events (VTE). [ 2 , 3 , 4 ] Patients undergoing major surgery already face a heightened risk of developing VTE, including deep-vein thrombosis and pulmonary embolism. [ 5 ] When obesity is present, this risk further increases, making patients with obesity more vulnerable to VTE and other adverse events during and after surgery. Several factors, including patient’s pre-existing conditions and the type of surgery performed, can influence the likelihood of both VTE and bleeding complications. [ 6 , 7 , 8 ] The risk of VTE remains particularly high within the first 30 days following hospital discharge. [ 9 , 10 , 11 ] In patients with obesity, this risk is estimated to be more than twice as high as in those without obesity and is further amplified when combined with additional thrombotic risk factors. [ 12 , 13 ] Pharmacological thromboprophylaxis is generally warranted in patients undergoing major orthopedic or cancer surgery [ 5 ] However, RCTs and other studies provide very limited evidence regarding thromboprophylaxis in the population with obesity (BMI 40 kg/m 2 or more). [ 14 , 15 , 16 , 17 , 18 ] For example, the American Society for Metabolic and Bariatric Surgery (ASMBS) guidelines recommend metabolic and bariatric surgery for patients with BMI ≥ 30 kg/m 2 ; however, the ASMBS does not provide specific guidelines for thromboprophylaxis following surgery in patients with obesity. [ 19 ] While it is recognized that the risk of VTE continues for extended periods of post-surgery hospital stay, there is no consensus regarding optimal VTE prophylaxis regimen in patients with obesity. [ 4 , 20 , 21 ] An evaluation of the risk for VTE and bleeding in this population is therefore critical for guiding VTE prophylaxis. [ 22 , 23 ] In this study, we aimed to describe the dose and duration of thromboprophylaxis with the low molecular weight heparin, enoxaparin, prescribed in usual clinical practice for hospitalized surgical patients with obesity who underwent a surgical procedure, and to assess risk factors and time-course of event rates for postoperative VTE and major bleeding (MB). Methods Study Design This study used a population drawn from the Optum Market Clarity database and represents individuals in the USA enrolled in health plans including private and Medicare Advantage, the latter being a private plan that contracts with Medicare and provides all of the benefits of Medicare part A (hospital insurance), Medicare part B (supplementary medical insurance, and often Medicare part D (privately sponsored prescription drug plans). [ 24 ] The database comprises linked information from electronic health records, inpatient and outpatient claims, prescriptions, laboratory tests, and plan enrollment. Patients hospitalized for elective or emergency surgery (abdominal/pelvic, orthopedic, and thoracic) between 28th February 2010 and 30th June 2021 and receiving enoxaparin thromboprophylaxis since admission were initially selected before the application of subsequent selection criteria (Fig. 1 ). If a patient had multiple qualifying hospitalizations, one was selected at random to facilitate the interpretation of the cohort as being comprised of unique patients. [ 25 ] However, patients in this analysis had at least one, and could have more than one surgery/type of surgery during their hospitalization. Additional inclusion criteria were hospitalization for a major surgery, age ≥ 18 years, ≥ 1-year of continuous enrollment in a health plan prior to index, and BMI ≥ 30 kg/m 2 . Patients were excluded if they had VTE or a MB event 90-days prior to index, major surgery within − 2 to − 90 days prior to index, ongoing anticoagulant therapy (medication supply within − 2 to − 32 days prior to index), atrial fibrillation, chronic kidney disease (CKD) stages IV and V (identified through diagnoses codes or estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m 2 ), or dialysis. Index hospitalization was characterized by the patient’s reason for hospitalization, length of stay (LOS), and intensive care unit (ICU) stay. The index date was defined as the start of inpatient enoxaparin thromboprophylaxis. Clinical conditions were identified from medical diagnosis and procedure codes during the 1-year baseline period prior to index enoxaparin initiation. Ongoing medication use was ascertained from medication supply within 90 days of index; a 30-day grace period was allowed after the end of days of supply. Duration of thromboprophylaxis represented the time from first enoxaparin administration to either the last administration in hospital, or the last day of medication supply if the patient received post-discharge thromboprophylaxis. If there was an interruption of ≤ 2 days, the duration of thromboprophylaxis was assumed as continuous. Patients were categorized as receiving a usual or standard dose if the daily dose administered at index was ≤ 40mg, while those who received > 40mg were categorized as receiving a higher dose. The outcome of endpoint was VTE, characterized as a new onset event occurring in either the inpatient or outpatient settings, and the safety outcome was MB, characterized as a new onset event in the inpatient setting. The ascertainment of VTE and MB endpoints was based on an algorithm that utilized diagnosis codes along with information on the setting (inpatient or outpatient). To determine the VTE endpoint, we first reviewed and included all ICD-9 and ICD-10 codes that are specific to acute pulmonary embolism or deep vein thrombosis (DVT), removing all DVT codes that did not explicitly mention deep veins or identified veins that are deep (e.g., femoral). Next, we also removed codes that explicitly mentioned chronic. This set was used for identification of VTE events in inpatient setting. From this set, we then retained only those codes that explicitly mentioned acute onset event or pulmonary embolism in the definition and used these codes in outpatient setting. Further explanation as well as the final list of codes (Table S1 ) can be found in the supplement. When determining the MB endpoint, any code indicating bleeding in an area or organ (critical or non-critical) was considered as major bleed if it occurred in the primary position on a claim in an inpatient setting. A subset of these codes was then considered as major bleeding for inpatient non-primary position. Any code explicitly mentioning “chronic” was not considered for non-primary position, and conversely any code explicitly mentioning “acute” was retained for non-primary position. Compartment syndrome was considered as MB if hemorrhage or hematoma occurred during the same hospitalization. Other codes were considered non-major bleeds and were used for baseline characterization of history of non-major bleeding. Detailed explanation as well as the final list of codes (Table S2) can be found in the supplement. Statistical Analysis The algorithm summarized in Fig. 1 was informed by prior studies and refined by coauthors to ensure specificity for identifying new onset VTE and MB events. Patients were followed for VTE and MB events for up to 90 days from index, with censoring criteria defined as death, disenrollment from the health plan, or the end of the 90-day follow-up period, whichever came first. Cumulative incidence of VTE and MB events were estimated via survival analysis (1 – Kaplan-Meier [KM]). Cox proportional hazards models were utilized to investigate the association of baseline conditions with the risk of VTE and MB. The reported set of risk factors represented those that were retained after application of backward variable selection process (with p < 0.05) in the Cox models for either VTE or MB using Python (version 3.9.3) statistical software. Results Study Population A total of 30,492 patients were selected based on the study inclusion criteria (Fig. 1 ). Baseline characteristics for the surgery group stratified by the type of index surgery and enoxaparin dosage are depicted in Table 1 . Most patients were females, accounting for 67.6% of the population. A quarter (24.4%) of the patients were aged 65 and over. Patients with a BMI > 40 kg/m2 comprised 41% of the group. Hypertension was the most prevalent comorbidity at 53.5%. The most used medications were anticoagulants (within 3 months of index) (35.5%), and angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) (27.9%). Table 1 Baseline characteristics for patients with obesity undergoing surgery by type of surgery. Surgery Type a Enoxaparin Dose b Total, N = 30,492 Abdominal/Pelvic N = 17,544 Orthopedic N = 11,582 Thoracic N = 1,749 Usual Dose ≤ 40mg per day , N = 12,058 High Dose >40mg per day , N = 18,300 Demographics Female sex N (%) 73.4 60.5 54.0 68.7 67.0 67.6 Age, years (%) 18—39 years 23.6 4.7 15.2 17.6 15.2 16.12 40—64 years 62.2 55.8 56.9 59.4 59.5 59.49 65—75 years 10.9 28.2 20.6 16.4 18.8 17.88 >75 years 3.3 11.4 7.2 6.6 6.5 6.5 Index Hospitalization Characteristics Length of hospital stay (days), median (IQR) 3 (2–5) 3 (3–4) 6 (4–11) 3 (2–5) 3 (3–5) 3 (2–5) Admission to enoxaparin start (days), median (IQR) 0 (0–1) 1 (1–1) 1 (0–1) 1 (0–1) 1 (0–1) 1 (0–1) Enoxaparin starts to discharge (days), median (IQR) 3 (2–4) 2 (2–3) 6 (3–10) 3 (2–4) 3 (2–4) 3 (2–4) Duration of prophylaxis with enoxaparin, median and IQR 2 (2–4) 2 (2–3) 4 (2–9) 2 (2–3) 3 (2–8) 2 (2–4) ICU/ CCU Stay, N (%) 11.1 8.2 70.8 12.6 13.5 13.1 Patients with enoxaparin Rx post discharge, N (%) 1.6 6.0 1.3 3.8 2.8 3.2 BMI kg/m 2 (24 months prior to index), N (%) 30 to 34.9 26.7 45.7 50.2 37.7 33.3 35.0 35-39.9 21.1 28.5 24.6 23.9 24.1 24.1 >40 52.1 25.8 25.2 38.3 42.7 40.9 Clinical Conditions Stroke and CBVD Hemorrhagic stroke 0.1 0.1 0.3 0.1 0.2 0.1 Ischemic stroke 1.0 1.4 3.3 1.2 1.3 1.3 Unspecified stroke or CBVD without stroke 3.0 4.9 9.1 3.5 4.4 4.1 Thrombophilia 0.7 0.8 0.5 0.4 1.0 0.8 Severe varicosities 1.7 2.4 1.5 1.8 2.1 2.0 History of cancer 15.8 8.4 27.4 12.5 14.5 13.7 Gastroduodenal ulcer 14.3 4.0 6.1 9.7 10.1 10.0 Lower limb paralysis 0.2 0.1 0.3 0.2 0.2 0.2 Central venous catheter 2.8 1.5 4.3 2.0 2.6 2.4 Heart failure 2.2 2.8 7.3 2.6 2.8 2.7 COPD 6.5 7.5 26.4 8.3 7.8 8.0 CKD stage III 9.0 12.2 16.7 11.1 10.3 10.6 CHD 7.9 12.1 16.8 9.8 10.0 10.0 Drug misuse disorder c 14.8 13.3 31.0 14.9 15.3 15.2 HIV infection 1.2 0.6 1.2 1.3 0.8 1.0 History of tobacco use 49.1 49.3 55.6 50.9 47.9 49.6 Diabetes 24.7 21.8 27.0 23.9 23.7 23.8 Immuno-hematologic conditions d 1.0 0.5 1.5 0.8 0.9 0.8 Peripheral vascular disease 3.8 5.8 6.3 5.1 4.5 4.7 Moderate/severe chronic liver disease 11.5 4.0 7.8 8.1 8.8 8.5 History of VTE 4.2 6.3 4.3 4.0 5.9 5.2 History of Bleeding Major bleeding 0.6 0.7 1.4 0.6 0.7 0.7 Nonmajor bleeding 17.8 6.8 11.8 14.2 12.8 13.4 Medication Use d Anticoagulants e 31.3 42.7 31.3 16.5 47.9 35.5 ACEi/ ARB 23.9 34.0 27.4 26.5 28.8 27.9 Beta blockers 16.5 23.4 23.5 22.1 17.6 19.5 Calcium channel blockers (CCBs) 9.5 16.1 14.9 13.1 11.7 12.3 Statins 15.7 28.5 24.1 18.9 22.2 20.9 Antiplatelets f 0.7 1.4 2.9 1.2 1.0 1.1 Hormone replacement therapy 2.3 0.6 1.0 1.7 1.5 1.6 Abbreviations: ACEi, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor blockers; CBVD, cerebrovascular disease; COPD, chronic obstructive pulmonary disease; CKD, chronic kidney disease; CHD, coronary heart disease; HIV, human immunodeficiency virus; CCBs, calcium channel blockers; HR, hazard ratio; VTE, venous thromboembolism. a There are 30,875 surgeries for the 30,492 patients, as some were admitted for multiple surgery types. b 134 out of 30,492 patients in the surgery group had missing dosage. c Includes codes for nicotine dependence, opioid dependence, other psychoactive substance abuse, other illegal prescription drug abuse. d Includes anemia, cell aplasia, pancytopenia, bone marrow failure syndromes, agranulocytosis, genetic anomalies of leukocytes, severe combined immunodeficiency (SCID), Nezelof's syndrome, Wiskott-Aldrich syndrome, Di George's syndrome, acute graft-versus-host disease. e Within 3 months prior to index. f Within 30–90 days of index Dosage/Duration of Thromboprophylaxis For the 12,058 patients administered the standard dose of enoxaparin, 37.7% had a BMI of 30-34.9 kg/m2, 23.9% had a BMI of 35-39.9 kg/m2, and 38.3% had a BMI of 40 + kg/m 2 . Comparatively, the percentage of each group for the 18,300 patients given higher doses was 33.3%, 24.1%, and 42.7%, respectively. Median duration of thromboprophylaxis with enoxaparin was higher for the high dose population compared to the usual dose population (3 (IQR 2–8) vs. 2 (IQR 2–3) days). When comparing the subgroups of patients who received the high dose vs. the standard dose of enoxaparin, surgical patients with BMI > 40 kg/m 2 (42.7% vs. 38.3%), history of VTE (5.9% vs. 4.0%), history of cancer (14.5% vs. 12.5%), prior anticoagulant use (47.9% vs. 16.5%), and prior statin use (22.2% vs. 18.9%) received higher doses. Duration of Hospitalization and Thromboprophylaxis The median duration of hospitalization was 3 days (IQR, 2–5 days). The median duration of enoxaparin thromboprophylaxis was on average shorter than the inpatient stay − 2 days (IQR 2–4 days); 11% of patients received enoxaparin for at least 7 days, 4% received enoxaparin for at least 14 days, and only 1% of patients received enoxaparin for 30 days or more (Figure S1 ) Time-course, Event Rates and Risk Factors for VTE and MB The event rates for VTE and MB are summarized over time in Table S3. The cumulative VTE event rates were 0.6%, 1.6%, and 2.5% at 7, 30 and 90 days follow up and the MB event rates were 0.4%, 0.8%, and 1.2% respectively (Fig. 2 ). The highest cumulative incidences of both VTE and MB were observed following thoracic surgeries (4.9% and 2.5% respectively) (Figure S2), while the lowest VTE and MB event rates were observed following abdominal pelvic (1.7%) and orthopedic (0.7%) surgeries. Of these, 2.9% of VTE and 1% of MB for thoracic surgeries happened post-discharge, with 1.5% and 0.6% respectively for pelvic and orthopedic surgeries (Table S4). Results from multivariable analysis for associations between baseline characteristics and outcomes are shown in Table 2 . Hospitalization due to thoracic surgery was associated with higher rates of VTE (HR 2.61, 95% CI 2–3.4) as compared to hospitalizations with abdominal/pelvic surgeries. Patients > 75 years of age had a higher risk of both VTE and MB events, with HR 1.87 (95% CI 1.3–2.69) and HR 1.98 (95% CI 1.25–3.14), respectively. Prior history of VTE (HR 5.62, 95% CI 4.71–6.7) was a significant risk factor for VTE in the follow up. A history of cancer was similarly a significant risk factor for VTE (HR 1.6, 95% CI 1.32–1.93). History of major bleeding (HR 2.62, 95% CI 1.29–5.32), and non-major (HR 2.45, 95% CI 1.92–3.12) were most predictive of MB events in the follow-up period. Table 2 Patient Characteristics at Index Associated with the Occurrence of VTE and Major Bleeding During 1-90-days Post Index: Cox Proportional Hazards Model. N (%) VTE HR (95% CI) MB HR (95% CI) Abdominal/ Pelvic 17,544 (57.5) Reference Reference Orthopedic 11,582 (38.0) 1.86 (1.56–2.21) 0.5 (0.38–0.66) Thoracic 1,749 (5.7) 2.61 (2–3.4) 1.39 (0.97–1.98) Age, years 18–39 4,915 (16.1) Reference Reference 40–64 18,141 (59.5) 1.3 (0.99–1.72) 0.73 (0.53–0.99) 65–75 5,453 (17.9) 1.38 (1–1.91) 0.99 (0.66–1.49)a >75 1,983 (6.5) 1.87 (1.3–2.69) 1.98 (1.25–3.14) Sex, % Male 9,881 (32.4) 1.14 (0.97–1.33) 1.35 (1.07–1.69) BMI (kg/m²) 30 to 34.9 10,681 (35.0) – – 35-39.9 7,337 (24.1) 1.05 (0.88–1.26) a 1.13 (0.86–1.49) a >40 12,474 (40.9) 0.97 (0.81–1.17) a 0.97 (0.74–1.28) a Stroke and CBVD No stroke or CBVD 28,861 (94.6) Reference Reference Ischemic stroke 388 (1.3) 1.08 (0.65–1.8) a 1.87 (1.04–3.33) Unspecified stroke or CBVD without stroke 1,243 (4.1) 0.99 (0.73–1.38) a 1.73 (1.18–2.54) History of Cancer 4,170 (13.7) 1.60 (1.32–1.93) 0.97 (0.73–1.29) a Anemia 4,282 (14.0) 1.02 (0.83–1.25) a 1.13 (0.86–1.5) a CKD stage III 3,231 (10.6) 1.46 (1.2–1.78) 1.27 (0.94–1.71) a COPD 2,431 (8.0) 0.98 (0.75–1.27) a 1.52 (1.09–2.11) History of VTE 1,580 (5.2) 5.62 (4.71–6.7) 0.86 (0.52–1.40) a History of non-major bleeding 4,074 (13.4) 1.01 (0.81–1.26) a 2.45 (1.92–3.12) History of major bleeding 207 (0.7) 2 (1.13–3.55) 2.62 (1.29–5.32) ACEi/ARB 8,501 (27.9) 0.96 (0.81–1.14) a 0.97 (0.75–1.24) a Antiplatelets b 333 (1.1) 0.85 (0.45–1.62) a 2.39 (1.34–4.24) Abbreviations: HR, hazard ratio; CI, confidence interval; MB, major bleeding; CBVD, cerebrovascular disease; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; VTE, venous thromboembolism; ACEi, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor blocker a not statistically significant at 5% level b Additional variables were analyzed in the full model, but not included in the final table as they were not statistically significant at 5% level and/or clinically meaningful. The list is as follows: thrombophilia, history of tobacco use, coronary heart disease, central venous catheter, history of diabetes, lower limb paralysis, hormone replacement therapy, major hematological and immunological conditions, drug misuse disorder, anticoagulants, peripheral vascular disease, severe varicosities, history of a heart failure comorbidity, statins, hypertension, HIV, coagulation disorder, moderate or severe chronic liver disease, calcium channel blockers, gastroduodenal ulcers, beta blockers, Discussion Our study showed a non-negligible 90-day risk of VTE for patients with obesity in a surgical population (2.5%). Since there is a lack of specific guidelines’ recommendations on dosing and duration of pharmacological thromboprophylaxis in this patient population, a careful evaluation is warranted on whether prevalent practice patterns and recommended strategies are optimal for the reduction in the risk of VTE. The subgroup with the highest 90-day risk of VTE was thoracic surgery (4.9%). The highest net clinical value of VTE prophylaxis was in patients undergoing orthopedic surgeries, for whom high VTE and low MB risks were observed simultaneously. While we did not observe that VTE risk further increases with BMI among patients with obesity, similar to prior studies, we see a higher VTE risk among older patients with obesity and among patients with obesity who also have previous VTE history. [ 9 , 4 , 26 – 29 ]. Results of this study add to the limited prior evidence investigating thromboprophylaxis in patients with obesity. Average thromboprophylactic daily dose of enoxaparin in our study was 70 mg, with the highest average dose of enoxaparin observed in patients with orthopedic surgery (Figure S4). Though there are potential concerns over higher bleeding risk related to higher dose thromboprophylaxis, several previous studies have demonstrated the advantages of adjusting thromboprophylactic dosage to a patient’s weight to achieve adequate VTE control. [ 30 – 35 ] Prior studies also concluded that a higher dose of thromboprophylaxis is safe and resulted in a significant reduction of VTE risk compared to standard thromboprophylaxis in patients with obesity [ 33 , 36 , 37 ]. In our study, patients were followed for VTE and MB events for up to 90 days from the index, which is a longer follow up than seen in previous reports [ 10 , 11 ]. We have observed that around 80% of VTE events occurred post-discharge and 40% occurred between 30 and 90 days of follow-up. In the National Surgical Quality Improvement Program (NSQIP) post-discharge VTE only accounted for about a third of VTE database because the follow-up is limited to 30 days [ 38 ]; however, this study and several previous reports showed a high post-discharge incidence of VTE in surgical patients and VTE risk persists up to 90 days after surgery and beyond the hospital stay. [ 10 , 20 , 21 ] Therefore, extending VTE prophylaxis after discharge might significantly decrease the proportion of post-discharge VTE events with subsequently associated decreases in morbidity and mortality The ESAIC guidelines on peri-operative VTE prophylaxis in patients with obesity recommend higher doses of LMWH, particularly in patients with BMI > 40 or weight > 150 kg. It also recommends extending pharmacological prophylaxis for at least 10 days rather than limiting it to hospital stays for patients at high risk of VTE, such as patients with obesity. [ 39 ] A key strength of our study is the summary of characteristics and 90-day event rates from a large contemporary population. The study population was well classified in terms of clinical conditions and medications at baseline as the databases (electronic health records, claims, enrolment information, pharmacy, and labs) were linked. Linked database analysis offered high numbers of patients and covariates that increased the detection of post-discharge VTE and MB risk in patients. An extended and consistent follow-up period of 90 days was also taken to monitor VTE and MB, which evaluated the long-term postoperative VTE and MB risks following discharge from hospital in patients with obesity. We meticulously calibrated and enhanced the algorithm for the identification of VTE and MB over the methods used in other studies. Unlike most other studies which limit their population to patients with obesity who underwent bariatric surgery, our study assessed patients with obesity undergoing a broader range of surgeries. This analysis of patients in usual clinical practice may prove useful to multiple stakeholders, including payers, regulatory authorities, clinicians, and clinical guidelines committees for the purpose of identifying those at highest risk of VTE and MB despite being initiated on thromboprophylaxis. As this study was based on observational data, several limitations should be noted. First, it only included individuals in the USA who were enrolled under a commercial or Medicare Advantage health plan, which may not be an accurate representation of non-insured populations- those covered under a public insurance program other than Medicare Advantage (e.g., Medicaid and other Medicare plans), or international populations. Second, in contrast to the highly stringent criteria used in RCTs, the current analysis relied on an algorithm based on codes and other information available in the database to identify VTE and MB endpoints; therefore, we cannot completely rule out the possibility of misclassification, for example due to the impact of mechanical prophylaxis. Given that the entire population received enoxaparin, there is also the possibility of selection bias. This study did not look at death as an outcome as we did not link Optum data to the National Death Index; however, this is likely to be a minor limitation as fatal bleeds are expected to be rare. Finally, the risk factors in our study reflect patients’ status at index before follow-up; however, as the patient population represents hospitalized individuals, clinical characterization and risk factors could have changed over the course of hospitalization which are not accounted for in this study. Despite being initiated on enoxaparin prophylaxis, patients experienced a clinically meaningful 90-day risk for VTE, at 2.5%, suggesting a need for further evaluation of recommended strategies for thromboprophylaxis with special emphasis on patients hospitalized due to thoracic surgery and those with a history of cancer. Patients with prior history of VTE are more prone to developing VTE during their follow-up period. Further, select patient subgroups seem to have a beneficial risk-benefit profile for extended or high dose prophylaxis, and formal cost-effectiveness analysis would be beneficial to conduct. Risk stratification, such as using an augmented model with more clinical inputs based on these factors may help determine the optimal thromboprophylaxis strategy in surgical patients with obesity. Declarations Ethical Approval and Informed Consent This was a retrospective analysis using de-identified patient data and did not require ethical approvals. Competing Interests WA is on advisory boards for Astra Zeneca, Bayer, BMS-Pfizer, Norgine, Sanofi, and Viatris. MC reports grants from Pfizer, personal fees from BMS, Leo Pharma, Bayer, Pfizer, Anthos, Regeneron and Sanofi.YD, IK, MA are employees of Sanofi.EP is a consultant for Sanofi.JA and CS declare no interests, financial or otherwise. Funding This study was supported by Sanofi. Author Contribution All authors contributed equally as co-authors. YD, IK, and EP had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Acknowledgement We thank Dhaval Sanchala , Global Publication Lead at Sanofi, for coordination and support in the publication process, and Jared Miller, Associate at Axtria, for providing medical writing assistance for this manuscript. References World Obesity [Internet]. World Obesity Federation; c2022 [cited 2025 Feb 25]. Prevalence of Obesity; [about 3 screens]. 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Ageno W, Becattini C, Brighton T, Selby R, Kamphuisen PW. Cardiovascular risk factors and venous thromboembolism: a meta-analysis. Circulation. 2008 Jan 1;117(1):93-102. Stein PD, Beemath A, Olson RE. Obesity as a risk factor in venous thromboembolism. Am J Med. 2005 Sep;118(9):978-80. Martin K, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost. 2016 Jun;14(6):1308-13. McCaughan GJB, Favaloro EJ, Pasalic L, Curnow J. Anticoagulation at the extremes of body weight: choices and dosing. Expert Rev Hematol. 2018 Oct;11(10):817-828. Liu J, Qiao X, Wu M, Wang H, Luo H, Zhang H, et al. Strategies involving low-molecular-weight heparin for the treatment and prevention of venous thromboembolism in patients with obesity: A systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023 Mar 8;14:1084511. Brenner B, Hull R, Arya R, Beyer-Westendorf J, Douketis J, Elalamy I, et al. Evaluation of unmet clinical needs in prophylaxis and treatment of venous thromboembolism in high-risk patient groups: cancer and critically ill. Thromb J. 2019 Apr 15;17:6. Rocha AT, de Vasconcellos AG, da Luz Neto ER, Araújo DM, Alves ES, Lopes AA. Risk of venous thromboembolism and efficacy of thromboprophylaxis in hospitalized obese medical patients and in obese patients undergoing bariatric surgery. Obes Surg. 2006 Dec;16(12):1645-55. Eisenberg D, Shikora SA, Aarts E, Aminian A, Angrisani L, Cohen RV, et al. 2022 American Society for Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO): Indications for Metabolic and Bariatric Surgery. Surg Obes Relat Dis. 2022 Dec;18(12):1345-1356. Kazaure HS, Roman SA, Sosa JA. Association of postdischarge complications with reoperation and mortality in general surgery. Arch Surg. 2012 Nov;147(11):1000-7. Bouras G, Burns EM, Howell AM, Bottle A, Athanasiou T, Darzi A. Risk of Post-Discharge Venous Thromboembolism and Associated Mortality in General Surgery: A Population-Based Cohort Study Using Linked Hospital and Primary Care Data in England. PLoS One. 2015 Dec 29;10(12):e0145759. Anderson DR, Morgano GP, Bennett C, Dentali F, Francis CW, Garcia DA, et al. American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients. Blood Adv. 2019 Dec 10;3(23):3898-3944. Gould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e227S-e277S. El-Nahal W. An Overview of Medicare for Clinicians. J Gen Intern Med. 2020 Dec;35(12):3702-3706. Goldhaber SZ. Risk factors for venous thromboembolism. J Am Coll Cardiol. 2010 Jun 29;56(1):1-7. Ntinopoulou P, Ntinopoulou E, Papathanasiou IV, Fradelos EC, Kotsiou O, Roussas N, et al. Obesity as a Risk Factor for Venous Thromboembolism Recurrence: A Systematic Review. Medicina (Kaunas). 2022 Sep 16;58(9):1290. Parkin L, Sweetland S, Balkwill A, Green J, Reeves G, Beral V. Body mass index, surgery, and risk of venous thromboembolism in middle-aged women: a cohort study. Circulation. 2012 Apr 17;125(15):1897-904. Yang G, De Staercke C, Hooper WC. The effects of obesity on venous thromboembolism: A review. Open J Prev Med. 2012 Nov;2(4):499-509. Bartlett MA, Mauck KF, Daniels PR. Prevention of venous thromboembolism in patients undergoing bariatric surgery. Vasc Health Risk Manag. 2015 Aug 17;11:461-77. Karas LA, Nor Hanipah Z, Cetin D, Schauer PR, Brethauer SA, Daigle CR, et al. Assessment of empiric body mass index-based thromboprophylactic dosing of enoxaparin after bariatric surgery: evidence for dosage adjustment using anti-factor Xa in high-risk patients. Surg Obes Relat Dis. 2021 Jan;17(1):153-160.. Chang CK, Higgins RM, Rein L, Peppard WJ, Herrmann DJ, Kindel T. Effectiveness of Body Mass Index-Based Prophylactic Enoxaparin Dosing in Bariatric Surgery Patients. J Surg Res. 2023 Jul;287:168-175. Shelkrot M, Miraka J, Perez ME. Appropriate enoxaparin dose for venous thromboembolism prophylaxis in patients with extreme obesity. Hosp Pharm. 2014 Sep;49(8):740-7. Bickford A, Majercik S, Bledsoe J, Smith K, Johnston R, Dickerson J, et al. Weight-based enoxaparin dosing for venous thromboembolism prophylaxis in the obese trauma patient. Am J Surg. 2013 Dec;206(6):847-51, discussion 851-2. Deremiah E, Franco-Martinez C, Gamboa C, Sponhaltz K, Rippee L, Reveles K, et al. Effectiveness and Safety of High-Dose Thromboprophylaxis in Morbidly Obese Major Trauma Patients. Hosp Pharm. 2023 Feb;58(1):92-97. Altawil E, Alkofide H, Almohaini H, Alobeed A, Alhossan A. The use of enoxaparin as venous thromboembolism prophylaxis in bariatric surgery: A retrospective cohort study. Saudi Pharm J. 2022 Oct;30(10):1473-1478. Wang TF, Milligan PE, Wong CA, Deal EN, Thoelke MS, Gage BF. Efficacy and safety of high-dose thromboprophylaxis in morbidly obese inpatients. Thromb Haemost. 2014 Jan;111(1):88-93. Perrin A, Sheth H, Snyder V, Dailey H, Jovin F, Smith R. Evaluating Adequacy of VTE Prophylaxis Dosing with Enoxaparin for Overweight and Obese Patients on an Orthopedic-Medical Trauma Comanagement Service. South Med J. 2023 Apr;116(4):345-349. Castaldi M, George G, Turner P, McNelis J. NSQIP Impacts Patient Experience. J Patient Exp. 2020 Feb;7(1):89-95. Arcelus JI, Gouin-Thibault I, Samama CM. European guidelines on peri-operative venous thromboembolism prophylaxis: first update.: Chapter 10: Surgery in the obese patient. Eur J Anaesthesiol. 2024 Aug 1;41(8):607-611. Additional Declarations Competing interest reported. WA is on advisory boards for Astra Zeneca, Bayer, BMS-Pfizer, Norgine, Sanofi, and Viatris. MC reports grants from Pfizer, personal fees from BMS, Leo Pharma, Bayer, Pfizer, Anthos, Regeneron and Sanofi. YD, IK, MA are employees of Sanofi. EP is a consultant for Sanofi. JA and CS declare no interests, financial or otherwise. Supplementary Files SupplementaryFile.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 30 Dec, 2025 Reviews received at journal 22 Dec, 2025 Reviewers agreed at journal 10 Dec, 2025 Reviewers agreed at journal 13 Oct, 2025 Reviewers invited by journal 06 Oct, 2025 Editor assigned by journal 20 Aug, 2025 Submission checks completed at journal 20 Aug, 2025 First submitted to journal 01 Aug, 2025 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. 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12:24:02","extension":"html","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":130415,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7274037/v1/e46697681a6e543ced00353a.html"},{"id":93774238,"identity":"66a7dfc8-59c8-4f39-95bd-8798fe818036","added_by":"auto","created_at":"2025-10-17 12:24:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":129116,"visible":true,"origin":"","legend":"\u003cp\u003eSelection of the Study Population from Optum MarketClarity database\u003c/p\u003e\n\u003cp\u003eAF, atrial fibrillation; CKD, chronic kidney disease; VTE, venous thromboembolism\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7274037/v1/7fe2c756732c13034fd3b1ae.png"},{"id":93774234,"identity":"5afa745c-dfde-47bf-90cb-7f9b3568018f","added_by":"auto","created_at":"2025-10-17 12:24:02","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":49358,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier Cumulative Incidence of VTE and MB event rates\u003c/p\u003e\n\u003cp\u003eTime zero indicates enoxaparin initiation. VTE, venous thromboembolism.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7274037/v1/b4dbabae36760be244a5f769.png"},{"id":93774320,"identity":"9b4b15a2-5d04-424a-bfe2-4fe521ba50d9","added_by":"auto","created_at":"2025-10-17 12:24:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1439698,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7274037/v1/23539624-5dd3-4b66-9c3a-deb1500fb596.pdf"},{"id":93774250,"identity":"440b23e1-cc2d-4d7d-afb1-2097abaa05d1","added_by":"auto","created_at":"2025-10-17 12:24:04","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":474336,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFile.docx","url":"https://assets-eu.researchsquare.com/files/rs-7274037/v1/82dbb6a451ad195b22b497a8.docx"}],"financialInterests":"Competing interest reported. WA is on advisory boards for Astra Zeneca, Bayer, BMS-Pfizer, Norgine, Sanofi, and Viatris. \nMC reports grants from Pfizer, personal fees from BMS, Leo Pharma, Bayer, Pfizer, Anthos, Regeneron and Sanofi.\nYD, IK, MA are employees of Sanofi.\nEP is a consultant for Sanofi.\nJA and CS declare no interests, financial or otherwise.","formattedTitle":"Venous Thromboembolism and Bleeding Risk in a Population with Obesity Hospitalized for Surgery and Receiving Enoxaparin for Thromboprophylaxis","fulltext":[{"header":"Key Points","content":"\u003cp\u003e\u0026bull; Patients with obesity hospitalized for surgery are at high risk of VTE and MB.\u003c/p\u003e\u003cp\u003e\u0026bull; VTE rates estimated using claims data in this population were non-negligible.\u003c/p\u003e\u003cp\u003e\u0026bull; History of VTE and thoracic surgery were associated with a higher risk for VTE 90 days post discharge.\u003c/p\u003e\u003cp\u003e\u0026bull; Individual risk stratification is warranted to identify optimal dosage/duration.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eIn 2024, it was estimated that more than one billion individuals (880\u0026nbsp;million adults and 159\u0026nbsp;million children) worldwide have obesity. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Obesity, defined as body mass index (BMI)\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e, is a global epidemic linked to increased morbidity and mortality. It is also an independent risk factor for developing venous thromboembolic events (VTE). [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e\u003cp\u003ePatients undergoing major surgery already face a heightened risk of developing VTE, including deep-vein thrombosis and pulmonary embolism. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] When obesity is present, this risk further increases, making patients with obesity more vulnerable to VTE and other adverse events during and after surgery. Several factors, including patient\u0026rsquo;s pre-existing conditions and the type of surgery performed, can influence the likelihood of both VTE and bleeding complications. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] The risk of VTE remains particularly high within the first 30 days following hospital discharge. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] In patients with obesity, this risk is estimated to be more than twice as high as in those without obesity and is further amplified when combined with additional thrombotic risk factors. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e\u003cp\u003ePharmacological thromboprophylaxis is generally warranted in patients undergoing major orthopedic or cancer surgery [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] However, RCTs and other studies provide very limited evidence regarding thromboprophylaxis in the population with obesity (BMI 40 kg/m\u003csup\u003e2\u003c/sup\u003e or more). [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] For example, the American Society for Metabolic and Bariatric Surgery (ASMBS) guidelines recommend metabolic and bariatric surgery for patients with BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e; however, the ASMBS does not provide specific guidelines for thromboprophylaxis following surgery in patients with obesity. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] While it is recognized that the risk of VTE continues for extended periods of post-surgery hospital stay, there is no consensus regarding optimal VTE prophylaxis regimen in patients with obesity. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] An evaluation of the risk for VTE and bleeding in this population is therefore critical for guiding VTE prophylaxis. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eIn this study, we aimed to describe the dose and duration of thromboprophylaxis with the low molecular weight heparin, enoxaparin, prescribed in usual clinical practice for hospitalized surgical patients with obesity who underwent a surgical procedure, and to assess risk factors and time-course of event rates for postoperative VTE and major bleeding (MB).\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Design\u003c/h2\u003e\u003cp\u003eThis study used a population drawn from the Optum Market Clarity database and represents individuals in the USA enrolled in health plans including private and Medicare Advantage, the latter being a private plan that contracts with Medicare and provides all of the benefits of Medicare part A (hospital insurance), Medicare part B (supplementary medical insurance, and often Medicare part D (privately sponsored prescription drug plans). [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] The database comprises linked information from electronic health records, inpatient and outpatient claims, prescriptions, laboratory tests, and plan enrollment.\u003c/p\u003e\u003cp\u003ePatients hospitalized for elective or emergency surgery (abdominal/pelvic, orthopedic, and thoracic) between 28th February 2010 and 30th June 2021 and receiving enoxaparin thromboprophylaxis since admission were initially selected before the application of subsequent selection criteria (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). If a patient had multiple qualifying hospitalizations, one was selected at random to facilitate the interpretation of the cohort as being comprised of unique patients. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] However, patients in this analysis had at least one, and could have more than one surgery/type of surgery during their hospitalization. Additional inclusion criteria were hospitalization for a major surgery, age\u0026thinsp;\u0026ge;\u0026thinsp;18 years, \u0026ge; 1-year of continuous enrollment in a health plan prior to index, and BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e. Patients were excluded if they had VTE or a MB event 90-days prior to index, major surgery within \u0026minus;\u0026thinsp;2 to \u0026minus;\u0026thinsp;90 days prior to index, ongoing anticoagulant therapy (medication supply within \u0026minus;\u0026thinsp;2 to \u0026minus;\u0026thinsp;32 days prior to index), atrial fibrillation, chronic kidney disease (CKD) stages IV and V (identified through diagnoses codes or estimated glomerular filtration rate (eGFR)\u0026thinsp;\u0026lt;\u0026thinsp;30 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e), or dialysis.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eIndex hospitalization was characterized by the patient\u0026rsquo;s reason for hospitalization, length of stay (LOS), and intensive care unit (ICU) stay. The index date was defined as the start of inpatient enoxaparin thromboprophylaxis. Clinical conditions were identified from medical diagnosis and procedure codes during the 1-year baseline period prior to index enoxaparin initiation. Ongoing medication use was ascertained from medication supply within 90 days of index; a 30-day grace period was allowed after the end of days of supply. Duration of thromboprophylaxis represented the time from first enoxaparin administration to either the last administration in hospital, or the last day of medication supply if the patient received post-discharge thromboprophylaxis. If there was an interruption of \u0026le;\u0026thinsp;2 days, the duration of thromboprophylaxis was assumed as continuous. Patients were categorized as receiving a usual or standard dose if the daily dose administered at index was \u0026le;\u0026thinsp;40mg, while those who received\u0026thinsp;\u0026gt;\u0026thinsp;40mg were categorized as receiving a higher dose.\u003c/p\u003e\u003cp\u003eThe outcome of endpoint was VTE, characterized as a new onset event occurring in either the inpatient or outpatient settings, and the safety outcome was MB, characterized as a new onset event in the inpatient setting. The ascertainment of VTE and MB endpoints was based on an algorithm that utilized diagnosis codes along with information on the setting (inpatient or outpatient).\u003c/p\u003e\u003cp\u003eTo determine the VTE endpoint, we first reviewed and included all ICD-9 and ICD-10 codes that are specific to acute pulmonary embolism or deep vein thrombosis (DVT), removing all DVT codes that did not explicitly mention deep veins or identified veins that are deep (e.g., femoral). Next, we also removed codes that explicitly mentioned chronic. This set was used for identification of VTE events in inpatient setting. From this set, we then retained only those codes that explicitly mentioned acute onset event or pulmonary embolism in the definition and used these codes in outpatient setting. Further explanation as well as the final list of codes (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e) can be found in the supplement.\u003c/p\u003e\u003cp\u003eWhen determining the MB endpoint, any code indicating bleeding in an area or organ (critical or non-critical) was considered as major bleed if it occurred in the primary position on a claim in an inpatient setting. A subset of these codes was then considered as major bleeding for inpatient non-primary position. Any code explicitly mentioning \u0026ldquo;chronic\u0026rdquo; was not considered for non-primary position, and conversely any code explicitly mentioning \u0026ldquo;acute\u0026rdquo; was retained for non-primary position. Compartment syndrome was considered as MB if hemorrhage or hematoma occurred during the same hospitalization. Other codes were considered non-major bleeds and were used for baseline characterization of history of non-major bleeding. Detailed explanation as well as the final list of codes (Table S2) can be found in the supplement.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eThe algorithm summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e was informed by prior studies and refined by coauthors to ensure specificity for identifying new onset VTE and MB events. Patients were followed for VTE and MB events for up to 90 days from index, with censoring criteria defined as death, disenrollment from the health plan, or the end of the 90-day follow-up period, whichever came first. Cumulative incidence of VTE and MB events were estimated via survival analysis (1 \u0026ndash; Kaplan-Meier [KM]). Cox proportional hazards models were utilized to investigate the association of baseline conditions with the risk of VTE and MB. The reported set of risk factors represented those that were retained after application of backward variable selection process (with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in the Cox models for either VTE or MB using Python (version 3.9.3) statistical software.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStudy Population\u003c/h2\u003e\u003cp\u003eA total of 30,492 patients were selected based on the study inclusion criteria (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Baseline characteristics for the surgery group stratified by the type of index surgery and enoxaparin dosage are depicted in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Most patients were females, accounting for 67.6% of the population. A quarter (24.4%) of the patients were aged 65 and over. Patients with a BMI\u0026thinsp;\u0026gt;\u0026thinsp;40 kg/m2 comprised 41% of the group. Hypertension was the most prevalent comorbidity at 53.5%. The most used medications were anticoagulants (within 3 months of index) (35.5%), and angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) (27.9%).\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 for patients with obesity undergoing surgery by type of surgery.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eSurgery Type\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eEnoxaparin Dose \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eTotal,\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;30,492\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eAbdominal/Pelvic\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eN\u0026thinsp;=\u0026thinsp;17,544\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eOrthopedic\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eN\u0026thinsp;=\u0026thinsp;11,582\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eThoracic\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eN\u0026thinsp;=\u0026thinsp;1,749\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eUsual Dose\u0026thinsp;\u0026le;\u0026thinsp;40mg\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eper day\u003c/b\u003e,\u003c/p\u003e\u003cp\u003e\u003cb\u003eN\u0026thinsp;=\u0026thinsp;12,058\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eHigh Dose\u003c/b\u003e \u003c/p\u003e\u003cp\u003e\u003cb\u003e \u0026gt;40mg\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eper day\u003c/b\u003e,\u003c/p\u003e\u003cp\u003e\u003cb\u003eN\u0026thinsp;=\u0026thinsp;18,300\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDemographics\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale sex N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e73.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e54.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e68.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e67.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e67.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years (%)\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\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e18\u0026mdash;39 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e17.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e16.12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e40\u0026mdash;64 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e55.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e56.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e59.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e59.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e59.49\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e65\u0026mdash;75 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e18.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e17.88\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;75 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eIndex Hospitalization Characteristics\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLength of hospital stay (days), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (2\u0026ndash;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (3\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (4\u0026ndash;11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3 (2\u0026ndash;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 (3\u0026ndash;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3 (2\u0026ndash;5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdmission to enoxaparin start (days), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0\u0026ndash;1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1\u0026ndash;1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (0\u0026ndash;1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (0\u0026ndash;1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (0\u0026ndash;1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (0\u0026ndash;1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEnoxaparin starts to discharge (days), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (2\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (2\u0026ndash;3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (3\u0026ndash;10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3 (2\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 (2\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3 (2\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration of prophylaxis with enoxaparin, median and IQR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (2\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (2\u0026ndash;3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (2\u0026ndash;9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (2\u0026ndash;3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3 (2\u0026ndash;8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2 (2\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eICU/ CCU Stay, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e70.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatients with enoxaparin Rx post discharge, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e \u003cb\u003e(24 months prior to index), N (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e30 to 34.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e50.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e37.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e33.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e35.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e35-39.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e24.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e24.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e25.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e38.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e42.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e40.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eClinical Conditions\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eStroke and CBVD\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\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemorrhagic stroke\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIschemic stroke\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnspecified stroke or CBVD without stroke\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThrombophilia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSevere varicosities\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory of cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGastroduodenal ulcer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e10.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLower limb paralysis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCentral venous catheter\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeart failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOPD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCKD stage III\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e11.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e10.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCHD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e10.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDrug misuse disorder\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e31.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e15.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHIV infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory of tobacco use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e49.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e49.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e55.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e50.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e47.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e49.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e23.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e23.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eImmuno-hematologic conditions\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePeripheral vascular disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModerate/severe chronic liver disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory of VTE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistory of Bleeding\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\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMajor bleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNonmajor bleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMedication Use\u003c/b\u003e\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnticoagulants\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e31.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e47.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e35.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eACEi/ ARB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e26.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e28.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e27.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBeta blockers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e17.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e19.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium channel blockers (CCBs)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e12.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStatins\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e18.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e22.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e20.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntiplatelets\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHormone replacement therapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: ACEi, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor blockers; CBVD, cerebrovascular disease; COPD, chronic obstructive pulmonary disease; CKD, chronic kidney disease; CHD, coronary heart disease; HIV, human immunodeficiency virus; CCBs, calcium channel blockers; HR, hazard ratio; VTE, venous thromboembolism.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003ea\u003c/sup\u003e There are 30,875 surgeries for the 30,492 patients, as some were admitted for multiple surgery types. \u003csup\u003eb\u003c/sup\u003e 134 out of 30,492 patients in the surgery group had missing dosage. \u003csup\u003ec\u003c/sup\u003e Includes codes for nicotine dependence, opioid dependence, other psychoactive substance abuse, other illegal prescription drug abuse. \u003csup\u003ed\u003c/sup\u003e Includes anemia, cell aplasia, pancytopenia, bone marrow failure syndromes, agranulocytosis, genetic anomalies of leukocytes, severe combined immunodeficiency (SCID), Nezelof's syndrome, Wiskott-Aldrich syndrome, Di George's syndrome, acute graft-versus-host disease. \u003csup\u003ee\u003c/sup\u003e Within 3 months prior to index. \u003csup\u003ef\u003c/sup\u003e Within 30\u0026ndash;90 days of index\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDosage/Duration of Thromboprophylaxis\u003c/h3\u003e\n\u003cp\u003eFor the 12,058 patients administered the standard dose of enoxaparin, 37.7% had a BMI of 30-34.9 kg/m2, 23.9% had a BMI of 35-39.9 kg/m2, and 38.3% had a BMI of 40\u0026thinsp;+\u0026thinsp;kg/m\u003csup\u003e2\u003c/sup\u003e. Comparatively, the percentage of each group for the 18,300 patients given higher doses was 33.3%, 24.1%, and 42.7%, respectively. Median duration of thromboprophylaxis with enoxaparin was higher for the high dose population compared to the usual dose population (3 (IQR 2\u0026ndash;8) \u003cem\u003evs.\u003c/em\u003e 2 (IQR 2\u0026ndash;3) days). When comparing the subgroups of patients who received the high dose \u003cem\u003evs.\u003c/em\u003e the standard dose of enoxaparin, surgical patients with BMI\u0026thinsp;\u0026gt;\u0026thinsp;40 kg/m\u003csup\u003e2\u003c/sup\u003e (42.7% \u003cem\u003evs.\u003c/em\u003e 38.3%), history of VTE (5.9% \u003cem\u003evs.\u003c/em\u003e 4.0%), history of cancer (14.5% \u003cem\u003evs.\u003c/em\u003e 12.5%), prior anticoagulant use (47.9% \u003cem\u003evs.\u003c/em\u003e 16.5%), and prior statin use (22.2% \u003cem\u003evs.\u003c/em\u003e 18.9%) received higher doses.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eDuration of Hospitalization and Thromboprophylaxis\u003c/h2\u003e\u003cp\u003eThe median duration of hospitalization was 3 days (IQR, 2\u0026ndash;5 days). The median duration of enoxaparin thromboprophylaxis was on average shorter than the inpatient stay \u0026minus;\u0026thinsp;2 days (IQR 2\u0026ndash;4 days); 11% of patients received enoxaparin for at least 7 days, 4% received enoxaparin for at least 14 days, and only 1% of patients received enoxaparin for 30 days or more (Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e)\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eTime-course, Event Rates and Risk Factors for VTE and MB\u003c/h3\u003e\n\u003cp\u003eThe event rates for VTE and MB are summarized over time in Table S3. The cumulative VTE event rates were 0.6%, 1.6%, and 2.5% at 7, 30 and 90 days follow up and the MB event rates were 0.4%, 0.8%, and 1.2% respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The highest cumulative incidences of both VTE and MB were observed following thoracic surgeries (4.9% and 2.5% respectively) (Figure S2), while the lowest VTE and MB event rates were observed following abdominal pelvic (1.7%) and orthopedic (0.7%) surgeries. Of these, 2.9% of VTE and 1% of MB for thoracic surgeries happened post-discharge, with 1.5% and 0.6% respectively for pelvic and orthopedic surgeries (Table S4).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eResults from multivariable analysis for associations between baseline characteristics and outcomes are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Hospitalization due to thoracic surgery was associated with higher rates of VTE (HR 2.61, 95% CI 2\u0026ndash;3.4) as compared to hospitalizations with abdominal/pelvic surgeries. Patients\u0026thinsp;\u0026gt;\u0026thinsp;75 years of age had a higher risk of both VTE and MB events, with HR 1.87 (95% CI 1.3\u0026ndash;2.69) and HR 1.98 (95% CI 1.25\u0026ndash;3.14), respectively. Prior history of VTE (HR 5.62, 95% CI 4.71\u0026ndash;6.7) was a significant risk factor for VTE in the follow up. A history of cancer was similarly a significant risk factor for VTE (HR 1.6, 95% CI 1.32\u0026ndash;1.93). History of major bleeding (HR 2.62, 95% CI 1.29\u0026ndash;5.32), and non-major (HR 2.45, 95% CI 1.92\u0026ndash;3.12) were most predictive of MB events in the follow-up period.\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\u003ePatient Characteristics at Index Associated with the Occurrence of VTE and Major Bleeding During 1-90-days Post Index: Cox Proportional Hazards Model.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u003c/p\u003e\u003cp\u003e(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eVTE\u003c/p\u003e\u003cp\u003eHR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMB\u003c/p\u003e\u003cp\u003eHR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdominal/\u003c/p\u003e\u003cp\u003ePelvic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17,544 (57.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eReference\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eReference\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOrthopedic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11,582 (38.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.86\u003c/p\u003e\u003cp\u003e(1.56\u0026ndash;2.21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003cp\u003e(0.38\u0026ndash;0.66)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThoracic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,749\u003c/p\u003e\u003cp\u003e(5.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.61\u003c/p\u003e\u003cp\u003e(2\u0026ndash;3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.39\u003c/p\u003e\u003cp\u003e(0.97\u0026ndash;1.98)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge, years\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e18\u0026ndash;39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4,915\u003c/p\u003e\u003cp\u003e(16.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eReference\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eReference\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e40\u0026ndash;64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18,141\u003c/p\u003e\u003cp\u003e(59.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.3\u003c/p\u003e\u003cp\u003e(0.99\u0026ndash;1.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.73\u003c/p\u003e\u003cp\u003e(0.53\u0026ndash;0.99)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e65\u0026ndash;75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5,453\u003c/p\u003e\u003cp\u003e(17.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.38\u003c/p\u003e\u003cp\u003e(1\u0026ndash;1.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.99\u003c/p\u003e\u003cp\u003e(0.66\u0026ndash;1.49)a\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,983\u003c/p\u003e\u003cp\u003e(6.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.87\u003c/p\u003e\u003cp\u003e(1.3\u0026ndash;2.69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.98\u003c/p\u003e\u003cp\u003e(1.25\u0026ndash;3.14)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex, %\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9,881\u003c/p\u003e\u003cp\u003e(32.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.14\u003c/p\u003e\u003cp\u003e(0.97\u0026ndash;1.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.35\u003c/p\u003e\u003cp\u003e(1.07\u0026ndash;1.69)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI (kg/m\u0026sup2;)\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e30 to 34.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10,681\u003c/p\u003e\u003cp\u003e(35.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e35-39.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7,337\u003c/p\u003e\u003cp\u003e(24.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.05\u003c/p\u003e\u003cp\u003e(0.88\u0026ndash;1.26)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.13\u003c/p\u003e\u003cp\u003e(0.86\u0026ndash;1.49)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12,474\u003c/p\u003e\u003cp\u003e(40.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.97\u003c/p\u003e\u003cp\u003e(0.81\u0026ndash;1.17)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.97\u003c/p\u003e\u003cp\u003e(0.74\u0026ndash;1.28)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eStroke and CBVD\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo stroke or CBVD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28,861\u003c/p\u003e\u003cp\u003e(94.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eReference\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eReference\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIschemic stroke\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e388\u003c/p\u003e\u003cp\u003e(1.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.08\u003c/p\u003e\u003cp\u003e(0.65\u0026ndash;1.8)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.87\u003c/p\u003e\u003cp\u003e(1.04\u0026ndash;3.33)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnspecified stroke or CBVD without stroke\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,243\u003c/p\u003e\u003cp\u003e(4.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.99\u003c/p\u003e\u003cp\u003e(0.73\u0026ndash;1.38)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.73\u003c/p\u003e\u003cp\u003e(1.18\u0026ndash;2.54)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory of Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4,170\u003c/p\u003e\u003cp\u003e(13.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.60\u003c/p\u003e\u003cp\u003e(1.32\u0026ndash;1.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.97\u003c/p\u003e\u003cp\u003e(0.73\u0026ndash;1.29)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4,282\u003c/p\u003e\u003cp\u003e(14.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.02\u003c/p\u003e\u003cp\u003e(0.83\u0026ndash;1.25)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.13\u003c/p\u003e\u003cp\u003e(0.86\u0026ndash;1.5)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCKD stage III\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3,231\u003c/p\u003e\u003cp\u003e(10.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.46\u003c/p\u003e\u003cp\u003e(1.2\u0026ndash;1.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.27\u003c/p\u003e\u003cp\u003e(0.94\u0026ndash;1.71)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOPD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2,431\u003c/p\u003e\u003cp\u003e(8.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.98\u003c/p\u003e\u003cp\u003e(0.75\u0026ndash;1.27)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.52\u003c/p\u003e\u003cp\u003e(1.09\u0026ndash;2.11)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory of VTE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,580\u003c/p\u003e\u003cp\u003e(5.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.62\u003c/p\u003e\u003cp\u003e(4.71\u0026ndash;6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.86\u003c/p\u003e\u003cp\u003e(0.52\u0026ndash;1.40)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory of non-major bleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4,074\u003c/p\u003e\u003cp\u003e(13.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.01\u003c/p\u003e\u003cp\u003e(0.81\u0026ndash;1.26)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.45\u003c/p\u003e\u003cp\u003e(1.92\u0026ndash;3.12)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory of major bleeding\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e207\u003c/p\u003e\u003cp\u003e(0.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003cp\u003e(1.13\u0026ndash;3.55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.62\u003c/p\u003e\u003cp\u003e(1.29\u0026ndash;5.32)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eACEi/ARB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8,501\u003c/p\u003e\u003cp\u003e(27.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.96\u003c/p\u003e\u003cp\u003e(0.81\u0026ndash;1.14)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.97\u003c/p\u003e\u003cp\u003e(0.75\u0026ndash;1.24)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntiplatelets\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e333\u003c/p\u003e\u003cp\u003e(1.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.85\u003c/p\u003e\u003cp\u003e(0.45\u0026ndash;1.62)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.39\u003c/p\u003e\u003cp\u003e(1.34\u0026ndash;4.24)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: HR, hazard ratio; CI, confidence interval; MB, major bleeding; CBVD, cerebrovascular disease; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; VTE, venous thromboembolism; ACEi, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor blocker\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003e not statistically significant at 5% level \u003csup\u003eb\u003c/sup\u003e Additional variables were analyzed in the full model, but not included in the final table as they were not statistically significant at 5% level and/or clinically meaningful. The list is as follows: thrombophilia, history of tobacco use, coronary heart disease, central venous catheter, history of diabetes, lower limb paralysis, hormone replacement therapy, major hematological and immunological conditions, drug misuse disorder, anticoagulants, peripheral vascular disease, severe varicosities, history of a heart failure comorbidity, statins, hypertension, HIV, coagulation disorder, moderate or severe chronic liver disease, calcium channel blockers, gastroduodenal ulcers, beta blockers,\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study showed a non-negligible 90-day risk of VTE for patients with obesity in a surgical population (2.5%). Since there is a lack of specific guidelines\u0026rsquo; recommendations on dosing and duration of pharmacological thromboprophylaxis in this patient population, a careful evaluation is warranted on whether prevalent practice patterns and recommended strategies are optimal for the reduction in the risk of VTE. The subgroup with the highest 90-day risk of VTE was thoracic surgery (4.9%). The highest net clinical value of VTE prophylaxis was in patients undergoing orthopedic surgeries, for whom high VTE and low MB risks were observed simultaneously. While we did not observe that VTE risk further increases with BMI among patients with obesity, similar to prior studies, we see a higher VTE risk among older patients with obesity and among patients with obesity who also have previous VTE history. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR27 CR28\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eResults of this study add to the limited prior evidence investigating thromboprophylaxis in patients with obesity. Average thromboprophylactic daily dose of enoxaparin in our study was 70 mg, with the highest average dose of enoxaparin observed in patients with orthopedic surgery (Figure S4). Though there are potential concerns over higher bleeding risk related to higher dose thromboprophylaxis, several previous studies have demonstrated the advantages of adjusting thromboprophylactic dosage to a patient\u0026rsquo;s weight to achieve adequate VTE control. [\u003cspan additionalcitationids=\"CR31 CR32 CR33 CR34\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] Prior studies also concluded that a higher dose of thromboprophylaxis is safe and resulted in a significant reduction of VTE risk compared to standard thromboprophylaxis in patients with obesity [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn our study, patients were followed for VTE and MB events for up to 90 days from the index, which is a longer follow up than seen in previous reports [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. We have observed that around 80% of VTE events occurred post-discharge and 40% occurred between 30 and 90 days of follow-up. In the National Surgical Quality Improvement Program (NSQIP) post-discharge VTE only accounted for about a third of VTE database because the follow-up is limited to 30 days [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]; however, this study and several previous reports showed a high post-discharge incidence of VTE in surgical patients and VTE risk persists up to 90 days after surgery and beyond the hospital stay. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] Therefore, extending VTE prophylaxis after discharge might significantly decrease the proportion of post-discharge VTE events with subsequently associated decreases in morbidity and mortality\u003c/p\u003e\u003cp\u003eThe ESAIC guidelines on peri-operative VTE prophylaxis in patients with obesity recommend higher doses of LMWH, particularly in patients with BMI\u0026thinsp;\u0026gt;\u0026thinsp;40 or weight\u0026thinsp;\u0026gt;\u0026thinsp;150 kg. It also recommends extending pharmacological prophylaxis for at least 10 days rather than limiting it to hospital stays for patients at high risk of VTE, such as patients with obesity. [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eA key strength of our study is the summary of characteristics and 90-day event rates from a large contemporary population. The study population was well classified in terms of clinical conditions and medications at baseline as the databases (electronic health records, claims, enrolment information, pharmacy, and labs) were linked. Linked database analysis offered high numbers of patients and covariates that increased the detection of post-discharge VTE and MB risk in patients. An extended and consistent follow-up period of 90 days was also taken to monitor VTE and MB, which evaluated the long-term postoperative VTE and MB risks following discharge from hospital in patients with obesity. We meticulously calibrated and enhanced the algorithm for the identification of VTE and MB over the methods used in other studies. Unlike most other studies which limit their population to patients with obesity who underwent bariatric surgery, our study assessed patients with obesity undergoing a broader range of surgeries. This analysis of patients in usual clinical practice may prove useful to multiple stakeholders, including payers, regulatory authorities, clinicians, and clinical guidelines committees for the purpose of identifying those at highest risk of VTE and MB despite being initiated on thromboprophylaxis.\u003c/p\u003e\u003cp\u003eAs this study was based on observational data, several limitations should be noted. First, it only included individuals in the USA who were enrolled under a commercial or Medicare Advantage health plan, which may not be an accurate representation of non-insured populations- those covered under a public insurance program other than Medicare Advantage (e.g., Medicaid and other Medicare plans), or international populations. Second, in contrast to the highly stringent criteria used in RCTs, the current analysis relied on an algorithm based on codes and other information available in the database to identify VTE and MB endpoints; therefore, we cannot completely rule out the possibility of misclassification, for example due to the impact of mechanical prophylaxis. Given that the entire population received enoxaparin, there is also the possibility of selection bias. This study did not look at death as an outcome as we did not link Optum data to the National Death Index; however, this is likely to be a minor limitation as fatal bleeds are expected to be rare. Finally, the risk factors in our study reflect patients\u0026rsquo; status at index before follow-up; however, as the patient population represents hospitalized individuals, clinical characterization and risk factors could have changed over the course of hospitalization which are not accounted for in this study.\u003c/p\u003e\u003cp\u003eDespite being initiated on enoxaparin prophylaxis, patients experienced a clinically meaningful 90-day risk for VTE, at 2.5%, suggesting a need for further evaluation of recommended strategies for thromboprophylaxis with special emphasis on patients hospitalized due to thoracic surgery and those with a history of cancer. Patients with prior history of VTE are more prone to developing VTE during their follow-up period. Further, select patient subgroups seem to have a beneficial risk-benefit profile for extended or high dose prophylaxis, and formal cost-effectiveness analysis would be beneficial to conduct. Risk stratification, such as using an augmented model with more clinical inputs based on these factors may help determine the optimal thromboprophylaxis strategy in surgical patients with obesity.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthical Approval and Informed Consent\u003c/h2\u003e\n\u003cp\u003eThis was a retrospective analysis using de-identified patient data and did not require ethical approvals.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eWA is on advisory boards for Astra Zeneca, Bayer, BMS-Pfizer, Norgine, Sanofi, and Viatris. MC reports grants from Pfizer, personal fees from BMS, Leo Pharma, Bayer, Pfizer, Anthos, Regeneron and Sanofi.YD, IK, MA are employees of Sanofi.EP is a consultant for Sanofi.JA and CS declare no interests, financial or otherwise.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThis study was supported by Sanofi.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eAll authors contributed equally as co-authors. YD, IK, and EP had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eWe thank Dhaval Sanchala , Global Publication Lead at Sanofi, for coordination and support in the publication process, and Jared Miller, Associate at Axtria, for providing medical writing assistance for this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Obesity [Internet]. World Obesity Federation; c2022 [cited 2025 Feb 25]. Prevalence of Obesity; [about 3 screens]. Available from: https://www.worldobesity.org/about/about-obesity/prevalence-of-obesity. \u003c/li\u003e\n\u003cli\u003eWorld Health Organization [Internet]. WHO; c2025 [cited 2025 Jan 07]. WHO fact sheets: Obesity and overweight; [about 6 screens]. 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Strategies involving low-molecular-weight heparin for the treatment and prevention of venous thromboembolism in patients with obesity: A systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023 Mar 8;14:1084511.\u003c/li\u003e\n\u003cli\u003eBrenner B, Hull R, Arya R, Beyer-Westendorf J, Douketis J, Elalamy I, et al. Evaluation of unmet clinical needs in prophylaxis and treatment of venous thromboembolism in high-risk patient groups: cancer and critically ill. Thromb J. 2019 Apr 15;17:6.\u003c/li\u003e\n\u003cli\u003eRocha AT, de Vasconcellos AG, da Luz Neto ER, Ara\u0026uacute;jo DM, Alves ES, Lopes AA. Risk of venous thromboembolism and efficacy of thromboprophylaxis in hospitalized obese medical patients and in obese patients undergoing bariatric surgery. 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PLoS One. 2015 Dec 29;10(12):e0145759.\u003c/li\u003e\n\u003cli\u003eAnderson DR, Morgano GP, Bennett C, Dentali F, Francis CW, Garcia DA, et al. American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients. Blood Adv. 2019 Dec 10;3(23):3898-3944.\u003c/li\u003e\n\u003cli\u003eGould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e227S-e277S.\u003c/li\u003e\n\u003cli\u003eEl-Nahal W. An Overview of Medicare for Clinicians. J Gen Intern Med. 2020 Dec;35(12):3702-3706. \u003c/li\u003e\n\u003cli\u003eGoldhaber SZ. Risk factors for venous thromboembolism. J Am Coll Cardiol. 2010 Jun 29;56(1):1-7.\u003c/li\u003e\n\u003cli\u003eNtinopoulou P, Ntinopoulou E, Papathanasiou IV, Fradelos EC, Kotsiou O, Roussas N, et al. Obesity as a Risk Factor for Venous Thromboembolism Recurrence: A Systematic Review. Medicina (Kaunas). 2022 Sep 16;58(9):1290.\u003c/li\u003e\n\u003cli\u003eParkin L, Sweetland S, Balkwill A, Green J, Reeves G, Beral V. Body mass index, surgery, and risk of venous thromboembolism in middle-aged women: a cohort study. Circulation. 2012 Apr 17;125(15):1897-904.\u003c/li\u003e\n\u003cli\u003eYang G, De Staercke C, Hooper WC. The effects of obesity on venous thromboembolism: A review. Open J Prev Med. 2012 Nov;2(4):499-509.\u003c/li\u003e\n\u003cli\u003eBartlett MA, Mauck KF, Daniels PR. Prevention of venous thromboembolism in patients undergoing bariatric surgery. Vasc Health Risk Manag. 2015 Aug 17;11:461-77.\u003c/li\u003e\n\u003cli\u003eKaras LA, Nor Hanipah Z, Cetin D, Schauer PR, Brethauer SA, Daigle CR, et al. Assessment of empiric body mass index-based thromboprophylactic dosing of enoxaparin after bariatric surgery: evidence for dosage adjustment using anti-factor Xa in high-risk patients. Surg Obes Relat Dis. 2021 Jan;17(1):153-160..\u003c/li\u003e\n\u003cli\u003eChang CK, Higgins RM, Rein L, Peppard WJ, Herrmann DJ, Kindel T. Effectiveness of Body Mass Index-Based Prophylactic Enoxaparin Dosing in Bariatric Surgery Patients. J Surg Res. 2023 Jul;287:168-175.\u003c/li\u003e\n\u003cli\u003eShelkrot M, Miraka J, Perez ME. Appropriate enoxaparin dose for venous thromboembolism prophylaxis in patients with extreme obesity. Hosp Pharm. 2014 Sep;49(8):740-7.\u003c/li\u003e\n\u003cli\u003eBickford A, Majercik S, Bledsoe J, Smith K, Johnston R, Dickerson J, et al. Weight-based enoxaparin dosing for venous thromboembolism prophylaxis in the obese trauma patient. Am J Surg. 2013 Dec;206(6):847-51, discussion 851-2. \u003c/li\u003e\n\u003cli\u003eDeremiah E, Franco-Martinez C, Gamboa C, Sponhaltz K, Rippee L, Reveles K, et al. Effectiveness and Safety of High-Dose Thromboprophylaxis in Morbidly Obese Major Trauma Patients. Hosp Pharm. 2023 Feb;58(1):92-97.\u003c/li\u003e\n\u003cli\u003eAltawil E, Alkofide H, Almohaini H, Alobeed A, Alhossan A. The use of enoxaparin as venous thromboembolism prophylaxis in bariatric surgery: A retrospective cohort study. Saudi Pharm J. 2022 Oct;30(10):1473-1478.\u003c/li\u003e\n\u003cli\u003eWang TF, Milligan PE, Wong CA, Deal EN, Thoelke MS, Gage BF. Efficacy and safety of high-dose thromboprophylaxis in morbidly obese inpatients. Thromb Haemost. 2014 Jan;111(1):88-93.\u003c/li\u003e\n\u003cli\u003ePerrin A, Sheth H, Snyder V, Dailey H, Jovin F, Smith R. Evaluating Adequacy of VTE Prophylaxis Dosing with Enoxaparin for Overweight and Obese Patients on an Orthopedic-Medical Trauma Comanagement Service. South Med J. 2023 Apr;116(4):345-349.\u003c/li\u003e\n\u003cli\u003eCastaldi M, George G, Turner P, McNelis J. NSQIP Impacts Patient Experience. J Patient Exp. 2020 Feb;7(1):89-95.\u003c/li\u003e\n\u003cli\u003eArcelus JI, Gouin-Thibault I, Samama CM. European guidelines on peri-operative venous thromboembolism prophylaxis: first update.: Chapter 10: Surgery in the obese patient. Eur J Anaesthesiol. 2024 Aug 1;41(8):607-611.\u003cbr\u003e \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"obesity-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"obsu","sideBox":"Learn more about [Obesity Surgery](https://link.springer.com/journal/11695)","snPcode":"11695","submissionUrl":"https://submission.springernature.com/new-submission/11695/3","title":"Obesity Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7274037/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7274037/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e\u003cp\u003eObese patients hospitalized for surgery are at high risk of venous thromboembolism (VTE). The optimal dose and duration of thromboprophylaxis with low molecular weight heparin for these patients are uncertain.\u003c/p\u003e\u003ch2\u003eAims\u003c/h2\u003e\u003cp\u003eTo assess the time-course, rates and risk factors for VTE and major bleeding (MB) in a population of surgical patients with obesity receiving pharmacological thromboprophylaxis with enoxaparin.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003ePatients with body mass index (BMI)\u0026thinsp;\u0026gt;\u0026thinsp;30 kg/m\u003csup\u003e2\u003c/sup\u003e hospitalized with surgeries between 2010 and 2019 who received thromboprophylaxis with enoxaparin were selected from the US Optum database. Exclusion criteria were VTE, MB, or surgery in previous 90-days, and ongoing anticoagulant treatment or dual antiplatelet therapy. VTE and MB event rates over a 90-day follow-up post enoxaparin initiation were estimated via the Kaplan-Meier (KM) method. Risk factors associated with outcome events were identified via Cox proportional hazard models.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 30,492 patients met selection criteria (median age 55, IQR 48\u0026ndash;66), 12,058 patients received the standard dose, with 18,300 receiving higher doses. KM event rates at 90-days for VTE and MB were 2.5% and 1.2%, respectively. The highest VTE rates were observed in patients hospitalized for thoracic surgery (4.9%). History of VTE was the strongest predictor of post-surgery VTE (HR 5.58, 95% CI 4.69\u0026ndash;6.63) while history of MB was the strongest predictor of post-surgery bleeding (HR 2.71, 95% CI 1.34\u0026ndash;5.48).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe rates of VTE are non-negligible in surgical patients with obesity receiving thromboprophylaxis with enoxaparin. Individual risk stratification is warranted to identify optimal doses/duration of pharmacologic thromboprophylaxis.\u003c/p\u003e","manuscriptTitle":"Venous Thromboembolism and Bleeding Risk in a Population with Obesity Hospitalized for Surgery and Receiving Enoxaparin for Thromboprophylaxis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-17 12:23:40","doi":"10.21203/rs.3.rs-7274037/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-30T15:24:52+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-22T18:08:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"49915868028919588050014993162081384398","date":"2025-12-10T15:23:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"256706507274987225359067279710295306044","date":"2025-10-13T11:30:59+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-06T06:48:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-21T00:40:25+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-20T06:08:57+00:00","index":"","fulltext":""},{"type":"submitted","content":"Obesity Surgery","date":"2025-08-01T19:36:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"obesity-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"obsu","sideBox":"Learn more about [Obesity Surgery](https://link.springer.com/journal/11695)","snPcode":"11695","submissionUrl":"https://submission.springernature.com/new-submission/11695/3","title":"Obesity Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a7b795ca-94d4-434b-9af8-b4828f03bdc4","owner":[],"postedDate":"October 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-13T16:08:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-17 12:23:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7274037","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7274037","identity":"rs-7274037","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}