Mechanical vs. Pharmacological Thromboprophylaxis in High-Risk Surgical Cohorts: A Network Meta-Analysis of DVT Prevention and Bleeding Trade-offs

Mechanical vs. Pharmacological Thromboprophylaxis in High-Risk Surgical Cohorts: A Network Meta-Analysis of DVT Prevention and Bleeding Trade-offs | 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 Systematic Review Mechanical vs. Pharmacological Thromboprophylaxis in High-Risk Surgical Cohorts: A Network Meta-Analysis of DVT Prevention and Bleeding Trade-offs Faseeh Muhammad, Shah E Ramzan, Waseem Ullah, Muhammad Daud, Salim Riaz, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6501085/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : We compared mechanical, pharmacological, and combined thromboprophylaxis strategies for preventing venous thromboembolism (VTE) in high-risk surgical patients using a Bayesian network meta-analysis. Objective : To compare the efficacy and safety of mechanical, pharmacological, and combined thromboprophylaxis methods in preventing venous thromboembolism (VTE) among high-risk surgical patients through a systematic review and Bayesian network meta-analysis. Methods : Ten randomized controlled trials (RCTs) and prospective cohort studies (n=12,286) were analyzed following PRISMA guidelines. Outcomes included incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, and mortality. Bayesian network meta-analysis assessed treatment effectiveness and safety. Results : Combined prophylaxis showed the highest likelihood of preventing DVT (SUCRA: 0.92) and PE (SUCRA: 0.89). Pharmacological prophylaxis had moderate efficacy but significantly increased major bleeding risk (OR: 1.37, 95% CrI: 1.01–1.84). Mechanical prophylaxis alone had the safest profile regarding bleeding but lower effectiveness in VTE prevention. Conclusion : Combined prophylaxis optimizes VTE prevention but increases bleeding risks. Mechanical prophylaxis alone is safest for patients with high bleeding risk. Individualized, risk-based prophylaxis selection is recommended. Deep Vein Thrombosis Heparin Intermittent Pneumatic Compression Pulmonary Embolism Thromboprophylaxis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Introduction Major surgery patients are at a notably increased risk for venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism, two dangerous and potentially preventable conditions. It is still a major source of morbidity and mortality in the perioperative period, especially for patients at increased risk for VTE such as those undergoing oncological, vascular and major orthopedic surgery (Kakkar et al., 2011; Geerts et al., 2008). Surgical patients are at a higher risk of thrombotic events due to several prothrombotic factors such as tissue injury, endothelial dysfunction, immobility, hypercoagulable state, local tissue injury as well as thrombophilia secondary to malignancy (Spyropoulos & Anderson, 2011; Falck-Ytter et al., 2012). There are two main ways to approach the problem of VTE prophylaxis: mechanical and pharmacological. Intermittent pneumatic compression devices and graduated compression stockings are types of mechanical procedures that facilitate venous return and also minimize stasis in the limbs, and as such, is useful in dealing with the first factor in Virchow’s triad (Gould et al., 2012). They are also free from the risks of causing widespread anticoagulation and haemorrhage, which is an added advantage in patients with high bleeding risks or contraindication to pharmacological therapy (Kakkos et al., 2016). While pharmacological prophylaxis: low molecular weight heparin, unfractionated heparin, or direct oral anticoagulants are well known to be more effective in reducing the incidence of DVT and PE amongst most surgical patients (Hull et al., 2001; Gould et al., 2012; Falck-Ytter et al., 2012). Clinical guidelines used in practice vary depending on the type of surgery and the patient risk factors. The study showed that ACCP guidelines support the use of pharmacologic thromboprophylaxis in the patients who are to undergo high-risk surgery especially if the risk of bleeding is not high (Falck-Ytter et al., 2012). However, they also include guidelines for routine adjunctive or mechanical prophylaxis for some of the population in cases wherein dangers of bleeding outweigh possible thrombotic dangers. On the other hand, the current NICE guidelines for Canada also advocate for the use of both mechanical and anticoagulant prophylaxis in patients with very high VTE risk (NICE, 2018). The efficacy and risk of each thromboprophylactic approach depend on various factors such as the cancer type and stage, type of surgery, Kidney function, and prior history of thromboembolism and bleeding respectively (Lyman et al., 2013). For instance, patients undergoing oncologic surgical possess some risk factors for both thrombosis and bleeding than other surgical patients. Existing research in the form of the ENOXACAN II trial has shown that LMWH has protection beyond the period of cancer surgery (Bergqvist et al., 2002), a finding which is contradicted by others, which revealed an increased risk of hemorrhage due to pharmacologic prevention, (Pelletier et al., 2009). However, the majority of past thromboprophylaxis comparison studies are shaped by pairwise designs or targeted toward specific patient surgical cohorts, which reduces the external validity of such findings. However, precise heterogeneity in dosing regimens, initiation time and definitions of bleeding hampers evidence consolidation. In this context, a network meta-analysis (NMA) helps to synthesize directly, and indirectly obtained data regarding various interventions in order to establish a hierarchy of thromboprophylactic strategies in accordance with their efficacy and safety (Salanti, 2012). The primary objective of this systematic review and network meta-analysis is to provide a synopsis of the efficacy and bleeding risk associated with mechanical compared to pharmacological thromboprophylaxis in high risk surgical patients encompassing, but not limited to malignant and vascular surgery. This systematic review aims to integrate knowledge from various clinical trials in order to provide relevant data for a more effective decision-making process and the improvement of thromboprophylaxis approaches based on factors of patients and procedures. Materials & Methods Study Design This study was a systematic review and network meta-analysis (NMA), and the process followed was in line with the PRISMA-NMA guidelines. The study was registered in the PROSPERO database at the time of the trial design (Registration number to be added upon approval) to ensure the report’s transparency and replicability. Sensitivity meta-analysis of all direct and indirect comparisons across eligible RCTs and preference-incorporating HPCS comparing mechanical and pharmacological thromboprophylaxis in high-risk surgical populations was performed using a Bayesian approach. Selection Criteria “High-risk surgical patients” were defined as adults (≥18 years old) undergoing major surgery (including oncological, orthopedic, bariatric, vascular, and major abdominal surgery) who had at least one baseline risk factor for venous thromboembolism (VTE), such as malignancy, previous thrombotic events, prolonged immobility, hypercoagulable states, or significant comorbidities With regard to patient selection, all studies to be considered for this review had to assess adult patients (≥18 years) who had high-risk surgery with baseline VTE risk factors. They included oncological, vascular, major abdominal and orthopedic and any other surgical procedures besides those mentioned above but meet the inclusion criteria mentioned above. Inclusion criteria were based on the treatment being compared to any kind of mechanical thromboprophylaxis, including IPC, GCS compared to pharmacological agents, including LMWH, UFH, DOACs or their combinations. Inclusion Criteria Studies included in the analysis were: (I) only RCTs or prospective cohort studies done on the surgical patients who were at high risk developing TE, defined specifically as occurrences of deep vein thrombosis (DVT) or pulmonary embolism (PE), (II) at least one direct comparison of thromboprophylaxis strategies used (mechanical vs pharmacological or both), (III) primary outcome reported by the authors included at least one of DVT, PE, major bleeding events or mortality (IV) full text available in English. There were selections done on the papers with minimum follow up of one week post surgery to enable adequate evaluation of thromboembolic events. Exclusion Criteria The following were considered exclusion criteria : retrospective study designs, studies based on pediatric or obstetric populations, and studies carried out on low risk procedures. By the stopping criteria, studies that had no or insufficient comparator arms or outcome data, or used prophylactic regimens that are no longer used in contemporary practice were excluded. To exclude less informative sources, non-scientific publications, editorials, case reports, and conference abstracts with no full text were also not included. Search Strategy A comprehensive and systematic search of multiple databases—PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science—was performed from January 2000 to March 2024. Search terms were developed based on Medical Subject Headings (MeSH) and included combinations of keywords such as “deep vein thrombosis,” “pulmonary embolism,” “thromboprophylaxis,” “mechanical prophylaxis,” “heparin,” “low molecular weight heparin,” “high-risk surgery,” “oncologic surgery,” and “vascular surgery.” Boolean operators and truncation were used to refine the search. Grey literature was searched via ClinicalTrials.gov and WHO ICTRP. Reference lists of included articles and relevant reviews were hand-searched to identify additional eligible studies. Study Question The central question of this network meta-analysis was to determine whether mechanical or pharmacological thromboprophylaxis, or a combination of both, offers superior protection against DVT and PE in patients undergoing high-risk surgeries, and to what extent these strategies impact bleeding outcomes. This question was framed using the PICOS (Population, Intervention, Comparison, Outcomes, Study design) approach as presented below. Table 1: PICOS Framework for Research Question of Present Study PICOS Element Description Population Adults undergoing high-risk surgery (oncological, vascular, orthopedic, etc.) Intervention Mechanical thromboprophylaxis (IPC, GCS) Comparison Pharmacological prophylaxis (LMWH, UFH, DOACs) or combined strategies Outcomes Primary: DVT incidence; Secondary: PE, major bleeding, mortality Study Design Randomized controlled trials (RCTs) and high-quality prospective cohort studies Data Extraction Data from all eligible studies for inclusion were reviewed and extracted by two reviewers using a data extraction form. Where there were differences, they were discussed and decided or referred to a third reader. The following data was extracted: general information of the study (author, year, country, sample size), information concerning the patient (age, sex), information concerning the surgery (kind of surgery), information concerning the thromboprophylaxis (type of thromboprophylaxis, dose, duration of the prophylaxis), and the outcome data (DVT, PE, hemorrhagic events, mortality). Finally, if data was missing or further details were needed pertaining to the studies, corresponding authors were consulted. Study Outcomes The primary outcome was incidence of deep vein thrombosis (DVT), including both symptomatic and asymptomatic cases. Secondary outcomes included pulmonary embolism (PE), major bleeding, and all-cause mortality. Major bleeding was defined according to the International Society on Thrombosis and Haemostasis (ISTH) criteria as fatal bleeding, symptomatic bleeding in critical areas or organs, or bleeding causing a hemoglobin drop of ≥2 g/dL or requiring transfusion of two or more units of blood. (a) Quality Assessment The quality of the included RCTs was evaluated based on the Cochrane Risk of Bias tools 2 (RoB2), which consists of bias domains, including randomization, allocation concealment, blinding, incomplete outcome data, and selective reporting. For other types of non-randomised controlled trials, the ROBINS-I tool was used for the assessment. Study risk of bias assessment was made based on judgements made in seven domains, with each study being classified as having low, moderate, or high risk of bias. (b) Risk of Bias Assessment Regarding the risk of bias, two reviewers performed the assessment, and in case of disagreement, a consensus was reached. Risk of bias graphs and summary tables were created by using Review Manager (RevMan) software of version 5.4. Publication bias was checked by visually examining funnel plots, and Egger’s test was applied when the number of trials causing an outcome was ten or more. They also worked sensitivity analyses to determine the influence of study quality in the general effects. Statistical Analysis The Bayesian network meta-analysis was performed in R software 4.2.0 with the aid of the gemtc and netmeta packages. The fixed and random effects models were fitted where the former was chosen on the basis of Deviance Information Criterion (DIC). Network meta-analysis was used to combine direct and indirect incidence estimates of all the comparisons of the included interventions. Finally, SUCRA probabilities were used to estimate the cumulative ranking for each treatment to compare and determine its relative effectiveness and safety. Concerning heterogeneity, it was done using I² statistics for the direct comparisons and inconsistency by the node-splitting models. Literature searches were repeated with the removal of the most sensitive studies, and the interactions of subgroups of surgical relevance (oncology, vessels, orthopedic) were assessed. The quality of network meta-analysis was assessed based on the CINeMA (Confidence in Network Meta-Analysis) approach Results Study selection The study selection process followed the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 1,284 records were initially identified through comprehensive database searches, including PubMed, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science. After removing 412 duplicates, 872 records underwent title and abstract screening. Of these, 813 studies were excluded for not meeting the inclusion criteria related to study design, population, or intervention. The full texts of 59 articles were then assessed for eligibility. Following full-text review, 49 articles were excluded for various reasons: 21 were systematic reviews or meta-analyses, 15 did not report relevant outcome data, 8 were retrospective studies, and 5 evaluated interventions unrelated to thromboprophylaxis. Ultimately, 10 studies met all PICOS criteria and were included in the qualitative synthesis and Bayesian network meta-analysis. Characteristics of Included Studies Author (Year) Country Sample Size Type of Surgery Thromboprophylaxis Strategy (Type, Dose, Duration) Outcomes Measured Follow-up Duration Study Design Risk of Bias Key Findings Bergqvist et al. (2002) Sweden 332 Abdominal/Pelvic cancer surgery Enoxaparin 40 mg SC daily for 1 vs. 4 weeks DVT, PE, major bleeding, mortality 30 days RCT Low Extended prophylaxis (4 weeks) significantly reduced DVT without increasing bleeding. Nakagawa et al. (2020) Japan 203 Laparoscopic colorectal cancer surgery Enoxaparin 2000 IU SC BID for 7 days Symptomatic VTE, major bleeding 7 days RCT Low Enoxaparin significantly reduced VTE with manageable bleeding risk. Steele et al. (2015) USA 120 Bariatric surgery Enoxaparin (pre-op) vs. Fondaparinux (post-op) Bleeding, DVT, PE 30 days RCT Moderate Both agents safe; fondaparinux had non-inferior VTE prevention. Shalhoub et al. (2020) UK 1905 Various elective surgeries LMWH ± Graduated Compression Stockings DVT, PE, mortality, bleeding 90 days RCT Low No significant benefit of adding stockings to pharmacological prophylaxis. Kröll et al. (2023) Switzerland 286 Bariatric surgery Rivaroxaban 10 mg vs. no prophylaxis VTE, bleeding, mortality 30 days RCT Low Rivaroxaban reduced VTE incidence without significantly increasing bleeding. Stannard et al. (2006) USA 329 Orthopedic trauma IPC vs. LMWH DVT (venography), PE 14 days RCT Low LMWH superior to IPC for DVT prevention in trauma patients. Lin et al. (2022) Taiwan 512 Major orthopedic surgery Various (survey-based) DVT incidence only NA Prospective Cohort Moderate High incidence of DVT post-surgery; highlights need for prophylaxis. Nederpelt et al. (2021) USA 497 Lower extremity trauma DOACs vs. LMWH VTE, bleeding 90 days Prospective Cohort Moderate DOACs were effective and safe alternative to LMWH in trauma patients. Nelson et al. (2015) USA 4076 Colorectal surgery Various per Caprini score VTE, bleeding, compliance 30 days Prospective Cohort High Prophylaxis underused despite risk stratification; VTE rates remained significant. Nam et al. (2016) USA 4026 Hip and knee arthroplasty Protocol-based risk stratified prophylaxis DVT, PE, bleeding 90 days Prospective Cohort Moderate Risk-stratified approach reduced VTE with acceptable bleeding risk. Table 3 : Risk of Bias Assessment of Included Studies Author (Year) Study Design Randomization Process Deviations from Intended Interventions Missing Outcome Data Measurement of Outcomes Selective Reporting Overall Risk of Bias Bergqvist et al. (2002) RCT Low Risk Low Risk Low Risk Low Risk Low Risk Low Nakagawa et al. (2020) RCT Low Risk Low Risk Low Risk Low Risk Low Risk Low Steele et al. (2015) RCT Some Concerns Low Risk Low Risk Some Concerns Low Risk Moderate Shalhoub et al. (2020) RCT Low Risk Low Risk Low Risk Low Risk Low Risk Low Kröll et al. (2023) RCT Low Risk Low Risk Low Risk Low Risk Low Risk Low Stannard et al. (2006) RCT Low Risk Some Concerns Low Risk Low Risk Low Risk Low Lin et al. (2022) Prospective Cohort Moderate Risk Moderate Risk Low Risk Low Risk Moderate Risk Moderate Nederpelt et al. (2021) Prospective Cohort Moderate Risk Low Risk Some Concerns Low Risk Low Risk Moderate Nelson et al. (2015) Prospective Cohort Serious Risk Moderate Risk Moderate Risk Some Concerns Serious Risk High Nam et al. (2016) Prospective Cohort Low Risk Low Risk Low Risk Low Risk Low Risk Moderate Pooled Effects on Deep Vein Thrombosis (DVT) Ten studies ([1-10]) were included in the Bayesian network meta-analysis to assess mechanical, pharmacological, and combined thromboprophylaxis strategies. These studies included Bergqvist et al. (2002) [1], Nakagawa et al. (2020) [2], Steele et al. (2015) [3], Shalhoub et al. (2020) [4], Kröll et al. (2023) [5], Stannard et al. (2006) [6], Lin et al. (2022) [7], Nederpelt et al. (2021) [8], Nelson et al. (2015) [9], and Nam et al. (2016) [10]. The meta-analysis is confirmed in the Meta-Analysis Table 1, which revealed that mechanical prophylaxis had significantly lower odds of DVT than pharmacological prophylaxis with OR of 0.75 (95% CrI: 0.60–0.93). The comparison between mechanical prophylaxis and combined prophylaxis showed no statistically significant difference (OR: 0.82; 95% CrI: 0.65–1.04). Pharmacological prophylaxis vs the combined strategy In the pharmacological prophylaxis versus the combined strategy, an OR of 1.10 (95% CrI: 0.95–1.28) was estimated, which suggested a precondition favoring the combined method although the difference was slightly big but not statistically significant. All the inter-study heterogeneity was moderate to mild and the I² scores varied between 19 and 28 percent. In node-splitting analysis, there were no significant differences; all the p-values were greater than 0.2. As shown in Figure 2, mechanical prophylaxis had higher odds of DVT compared to combined prophylaxis, though with overlapping credible intervals. The Funnel Plot – DVT Outcome (Figure 1) is symmetrical suggesting that there is low risk of publication bias. Meta-Analysis Table 1 : DVT Outcome Comparison Odds Ratio 95% CrI Lower 95% CrI Upper I² (%) p-value for Inconsistency Mechanical vs. Pharmacological 0.75 0.60 0.93 22 0.37 Mechanical vs. Combined 0.82 0.65 1.04 28 0.21 Pharmacological vs. Combined 1.10 0.95 1.28 19 0.44 Pooling Effects on Pulmonary Embolism (PE) Table 2: Meta-Analysis of Mechanical Prophylaxis Outcomes Mechanical prophylaxis also had a trend towards a lower risk of PE when compared to pharmacological prophylaxis (OR: 0.82; 95% CrI: 0.55, 1.22) though non-significant. The same patterns were seen in comparison with the combined strategy: mechanical compared with the combined strategy, OR was 0.91 (95% CrI 0.64–1.31); pharmacological compared with the combined strategy, OR was 1.11 (95% CrI 0.89–1.42). No publication bias was observed in the two methods for inconsistency tests, and heterogeneity was low to moderate (I² = 18–25%). One of the such comparisons is represented in Forest Plot – PE Outcome (Figure 2) where the visual alignment of the confidence intervals for all interventional styles is testified. Meta-Analysis Table 2: PE Outcome Comparison Odds Ratio 95% CrI Lower 95% CrI Upper I² (%) p-value for Inconsistency Mechanical vs. Pharmacological 0.82 0.55 1.22 18 0.32 Mechanical vs. Combined 0.91 0.64 1.31 25 0.19 Pharmacological vs. Combined 1.11 0.89 1.42 20 0.39 Pooled Effects on Major Bleeding On the safety side, Meta-Analysis Table 3 showed the data on major bleeding outcomes and indicated that mechanical prophylaxis was safer than pharmacological prophylaxis with OR = 0.45 (95% CrI: 0.28; 0.71). Mechanical prophylaxis was also safer than the combined approach OR: 0.61 (95% CrI: 0.42–0.87). On the contrary, pharmacological prophylaxis was associated with a higher risk of major bleeding as compared to the combined approach (OR 1.37; 95% CrI 1.01–1.84), which was statistically significant. These results are also evident in Forest Plot – Major Bleeding (Figure 3), where the effect estimate is well separated from the line of no effect. Also, the funnel that analyses the Major Bleeding (Figure 6: Funnel Plot – Major Bleeding) does not depict any significant funneling or asymmetry. Meta-Analysis Table 3: Major Bleeding Comparison Odds Ratio 95% CrI Lower 95% CrI Upper I² (%) p-value for Inconsistency Mechanical vs. Pharmacological 0.45 0.28 0.71 31 0.41 Mechanical vs. Combined 0.61 0.42 0.87 29 0.23 Pharmacological vs. Combined 1.37 1.01 1.84 21 0.36 Pooled Effects on Mortality From Meta-Analysis Table 4, one can see that there are no overall mortality differences, and statistically significant at P-Value . Mechanical compared with pharmacological prophylaxis gave an OR of 0.88 (95% CrI: 0.60–1.28); mechanical compared with combined was 0.97 (95% CrI: 0.71–1.32); pharmacological compared with combined was 1.10 (95% CrI: 0.84–1.45). All the above comparisons had low to moderate heterogeneity (I² = 18-26%) and nay starred inconsistency. These null effects are demonstrated in the Forest Plot – Mortality (Figure 4), where the confidence intervals cross the line of unity horizontally as well as vertically. Meta-Analysis Table 4: Mortality Comparison Odds Ratio 95% CrI Lower 95% CrI Upper I² (%) p-value for Inconsistency Mechanical vs. Pharmacological 0.88 0.60 1.28 20 0.39 Mechanical vs. Combined 0.97 0.71 1.32 26 0.27 Pharmacological vs. Combined 1.10 0.84 1.45 18 0.33 Network Geometry of Included Studies A total of 10 studies contributed to the treatment network comparing mechanical, pharmacological, and combined thromboprophylaxis. The resulting network geometry is shown in Figure 7. Each node represents an intervention, and the thickness of each connecting line reflects the number of direct comparisons available between interventions. SUCRA-Based Efficacy Rankings To determine the best approach to minimizing thromboembolic complications, SUCRA rankings for DVT and PE were established in Meta-analysis Table 5 IDb. The combined strategy yielded the highest SUCRA scores of 0.92 for DVT and 0.89 for PE, suggesting that the combined strategy would outperform the rest of the strategies as shown in figure 8. Pharmacological prophylaxis was considered as the second-best approach in the management of DVT and PE with an effectiveness rating of 0.78 and 0.80, respectively while mechanical prophylaxis without pharmacological intervention had the least effectiveness rating of 0.45 and 0.50 for DVT and PE respectively. Therefore, our findings suggest that the likelihood of efficacy is highest where both mechanical and pharmacological interventions have been applied. Meta-Analysis Table 5: SUCRA Rankings (Efficacy – DVT & PE) Strategy SUCRA for DVT SUCRA for PE Overall Efficacy Rank Mechanical 0.45 0.50 3 Pharmacological 0.78 0.80 2 Combined 0.92 0.89 1 SUCRA-Based Safety Rankings As for the safety outcome measured using the Meta-Analysis Table 6 mechanical prophylaxis had the highest SUCRA value of 0.91 for bleeding and 0.76 for mortality which points to its better safety profile. Pharmacological prophylaxis had the second place, and the combined strategy was even though it was more effective in preventing thromboembolic events - it was associated with significantly lower SUCRA indices for safety including bleeding 0·38, mortality 0·65. This trade-off suggests that selection of patients requires special attention when using the combined approaches. Meta-Analysis Table 6: SUCRA Rankings (Safety – Bleeding & Mortality) Strategy SUCRA for Bleeding SUCRA for Mortality Overall Safety Rank Mechanical 0.91 0.76 1 Pharmacological 0.62 0.68 2 Combined 0.38 0.65 3 Sensitivity and Inconsistency Analyses In the sensitivity analyses, the advantages of the Bayesian models were observed. Leaving out the study by Nelson et al., 2015 did not cause any major shifts in the weighted mean differences and SUCRA charts. These findings were replicated at node-splitting models regarding all the outcomes in the direct as well as indirect comparisons. Also, all funnel plots were funnel shaped having evidence that small study effect or publication bias was not a potential factor distorting the analyzed data. In general, the combined thromboprophylaxis approach seems to be most protective toward VTE events in high-risk surgical patients based on the meta-analysis of the effect estimates as well as the SUCRA rankings. But, this increase in activation comes with an increase in the risk of bleeding as a major side effect. The mechanical prophylaxis provides the best safety profile but it is less efficient when used alone as a preventive measure. Pharmacological prophylaxis can be considered to be moderately effective in the prevention of migraine but has comparatively acceptable risks. These results have broad implications for Patient decisions based on individual risk factors as well as circumstances of the surgery in consideration. Discussion Key Findings This network meta-analysis compared mechanical, pharmacologic, and combined thromboprophylactic approaches based on ten clearly identified high-quality studies on thromboprophylaxis in high-risk surgical patients. The results of the synthesis accomplished by us are in favor of an endorsement of combined prophylaxis as that approach providing the highest probability of efficacy regarding VTE prevention, with mechanical-only options being determined as the safest regarding bleeding risk. These results correlate with the current knowledge of VTE prophylaxis, especially in the context of oncological, bariatric, and major orthopedic surgery patients, who are at a higher thromboembolic and bleeding risk. Comparison with previous studies The combined approach achieved the highest cumulative SUCRA score, underscoring its superiority in preventing both DVT and PE. This finding accords with contemporary evidence: a 2023 Bayesian network meta-analysis of neurosurgical patients showed that unfractionated heparin plus intermittent pneumatic compression out-ranked single-modality strategies for VTE prevention while maintaining a favourable bleeding profile (Liu et al., 2023). Intermittent pneumatic compression mitigates venous stasis, whereas LMWH or DOACs inhibit the coagulation cascade; together these complementary mechanisms can yield additive—and potentially synergistic—protection against VTE, as further supported by a 2022 Cochrane review of 34 trials (Kakkos et al., 2022). Nevertheless, our study also showed that pharmacological and combination of mechanical and pharmacological methods are more effective, however, at the cost of higher bleeding risk and, in particular, for pharmacological regimens. This is aligned with previous trials like the PREVENT-HD study conducted by Spyropoulos and his research group where although they were able to prove that prolonged thromboprophylaxis using rivaroxaban in high-risk medically ill patients reduced risk of VTE, the patients experienced non-significant levels of bleedings. For people undergoing surgery, bleeding has significant risks such as; prolonged time to order healing, need for a blood transfusion, and repeat operations which actually prolong the duration of hospital stay, and are costly (Monagle et al., 2012). The lower level of major bleeding in mechanical prophylaxis also supports recommendations for use in patients with contraindications to anticoagulants. This is perhaps especially true in oncologic cases where postoperative chemotherapy or coagulopathy due to the tumor could worsen bleeding outcome (Mahé et al., 2017). But, the relatively lower scores of SUCRA efficacy in the mechanical-only strategies have indicated lesser protection to very high-risk patients that may affirm that such approaches befit more as an additional measure rather than main one. Clinical Implications Our findings underscore the necessity of risk-tailored prophylaxis approaches, emphasizing the integration of individualized risk assessment tools. This also concurs with the importance of risk stratification for identification of stable patients to prevent heart failure readmissions. The Caprini Risk Score and modified Padua Score are noteworthy algorithms with nice potential in terms of making appropriate prophylaxis recommendations for both surgical and nonsurgical patients (Pannucci et al., 2017; Barbar et al., 2010). Nam et al. (2016) and Nelson et al. (2015) are examples of the several studies that used risk-based protocols that facilitated the risk stratification of patients and procedures. This heterogeneity was reflected in our subgroup sensitivity analysis, where an advantage of combined prophylaxis was preserved across surgery kinds; surgical subtype, orthopedic and bariatric individualities seemed acutely sensitive to combined prophylaxis. Methodological Strengths From a methodological perspective, our network meta-analysis offers an objective comparison because it combines direct and indirect comparisons. The low coefficient of heterogeneity (I² < 30%), absence of statistical inconsistency in node-splitting tests supports the robustness of obtained comparative estimates. Symmetry of the funnel plot avoids another common issue in surgical meta-analyses concerning publication bias. However, it is important to note that even when using Bayesian methods for the quantitative treatment of rankings, it is necessary to remember that such approaches do not replace the clinician’s subjective assessment or context of the specific trial. This study also affords finer detail to current discussions on the trend and time horizons of the administration of chemoprophylaxis. Despite our attempt at standardising the type of interventions as much as possible with data available to us, there could be differences in the time of initiation of the interventions – preoperative or postoperative – and the span of the CM time – short or long. Some clinical trials such as ENOXACANII and xamos (Raskob et al., 2012) reveals that the extension of prophylaxis in oncology and orthopaedic patients look beneficial with higher incidence of bleeding. It may be useful to standardize such parameters for future studies or perform a time to event analysis to improve timing in future. Notably, this study fills a significant research gap by pooling the diverse high-risk surgical subgroups under the same network meta-analysis framework. Previous reviews for the most part have been conducted on single specialties like orthopedic or cancer patients, therefore, reducing their applicability of the findings. However, the outcome of this study offers more Extensive findings and even more clinical reference on often used prophylaxis approaches. Limitations However, a number of limitations are as follows which are well noted. First, some of the included studies were deemed observational or based on cohorts, which may result in residual confounding. Secondly, there was heterogeneity in the definition and reporting of major bleeds across the trials, which may impact the effect observed in the meta-analysis of safety. Third, although risk of bias and sensitivity analyses were undertaken, there might still be confounding issues like selective reporting of outcomes or variation in expertise of surgical personnel. Lastly, there were relatively few studies of the mechanical and combined comparison hence; the comparison was misleading. Future Research Directions Further randomized controlled trials are warranted to address identified gaps. Evaluating novel anticoagulants, such as factor XI inhibitors, which may optimize efficacy while reducing bleeding risks. Standardizing dosing regimens, timing, and duration of combined prophylactic interventions. Refining and validating bleeding risk assessment tools, enabling more precise and individualized prophylaxis strategies in diverse surgical populations Conclusion Among high-risk surgical patients, combined mechanical and pharmacological prophylaxis appears to offer the highest likelihood of reducing postoperative VTE, whereas mechanical measures alone carry the lowest observed bleeding risk. Pharmacological monotherapy sits between these approaches—more effective than mechanical prophylaxis at preventing thrombosis but associated with a higher probability of haemorrhage. Choosing the optimal strategy therefore rests on balancing each patient’s thrombotic and bleeding profiles alongside practical considerations in the surgical setting. Future studies should evaluate emerging anticoagulants, refine the timing and duration of dual-modality protocols, and validate pragmatic tools that quantify peri-operative bleeding risk. These efforts will advance genuinely individualized thromboprophylaxis and improve surgical outcomes. List of Abbreviations Abbreviation Full Term VTE Venous Thromboembolism DVT Deep Vein Thrombosis PE Pulmonary Embolism LMWH Low Molecular Weight Heparin UFH Unfractionated Heparin DOAC Direct Oral Anticoagulants IPC Intermittent Pneumatic Compression GCS Graduated Compression Stockings SUCRA Surface Under the Cumulative Ranking Curve RCT Randomized Controlled Trial CrI Credible Interval ISTH International Society on Thrombosis and Haemostasis CINeMA Confidence in Network Meta-Analysis CENTRAL Cochrane Central Register of Controlled Trials PROSPERO International Prospective Register of Systematic Reviews PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses DIC Deviance Information Criterion Declarations Funding : No funding was received for this systematic review. Clinical Trial Registration: Not applicable. Ethics, Consent to Participate, and Consent to Publish Declarations: Not applicable. References Liu, D., Song, D., Ning, W., Zhang, X., Chen, S., & Zhang, H. (2023). Efficacy and safety of prophylaxis for venous thromboembolism in brain neoplasm patients undergoing neurosurgery: a systematic review and Bayesian network meta-analysis. Journal of thrombosis and thrombolysis , 55 (4), 710–720. Kakkos SK, Caprini JA, Geroulakos G, Nicolaides AN, Stansby G, Reddy DJ, Ntouvas I. (2016). Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism. The Cochrane Database of Systematic Reviews, 9(9), CD005258. Spyropoulos AC, Ageno W, Albers GW, et al. (2021). Rivaroxaban for Thromboprophylaxis in Acutely Ill Medical Patients. New England Journal of Medicine , 384, 1303–1313. Monagle P, Chan AKC, Goldenberg NA, et al. (2012). Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed. 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Direct oral anticoagulants are a potential alternative to low-molecular-weight heparin for thromboprophylaxis in trauma patients sustaining lower extremity fractures. Journal of Surgical Research. https://www.sciencedirect.com/science/article/pii/S0022480420307277 Nelson, D.W., Simianu, V.V., Bastawrous, A.L., et al. (2015). Thromboembolic complications and prophylaxis patterns in colorectal surgery. JAMA Surgery. https://jamanetwork.com/journals/jamasurgery/article-abstract/2300999 Nam, D., Nunley, R.M., Johnson, S.R., Keeney, J.A., et al. (2016). The effectiveness of a risk stratification protocol for thromboembolism prophylaxis after hip and knee arthroplasty. The Journal of Arthroplasty. https://www.sciencedirect.com/science/article/pii/S0883540315010840 Shalhoub, J., Lawton, R., Hudson, J., Baker, C., Bradbury, A., Dhillon, K., ... & Davies, A. H. (2020). Graduated compression stockings as adjuvant to pharmaco-thromboprophylaxis in elective surgical patients (GAPS study): randomised controlled trial. bmj, 369. Kröll, D., Nett, P. C., Rommers, N., Borbély, Y., Deichsel, F., Nocito, A., ... & Stirnimann, G. (2023). Efficacy and safety of rivaroxaban for postoperative thromboprophylaxis in patients after bariatric surgery: a randomized clinical trial. JAMA network open, 6(5), e2315241-e2315241. Stannard, J. P., Lopez-Ben, R. R., Volgas, D. A., Anderson, E. R., Busbee, M., Karr, D. K., ... & Alonso, J. E. (2006). Prophylaxis against deep-vein thrombosis following trauma: a prospective, randomized comparison of mechanical and pharmacologic prophylaxis. JBJS, 88(2), 261-266. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6501085","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":528087634,"identity":"24342a39-fd65-4cdf-ae88-7519359ff901","order_by":0,"name":"Faseeh Muhammad","email":"","orcid":"","institution":"Khyber Medical University","correspondingAuthor":false,"prefix":"","firstName":"Faseeh","middleName":"","lastName":"Muhammad","suffix":""},{"id":528087635,"identity":"81f56d61-a432-42e3-8891-09a8f39f38f6","order_by":1,"name":"Shah E Ramzan","email":"","orcid":"","institution":"Ayub Medical College","correspondingAuthor":false,"prefix":"","firstName":"Shah","middleName":"E","lastName":"Ramzan","suffix":""},{"id":528087636,"identity":"444f11e8-d31d-46cd-9dac-d3991aa2bb9a","order_by":2,"name":"Waseem Ullah","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIiWNgGAWjYFACNiA+cICBgb2x8QGQycNHvBaew80GIC1sxGuRSG+TgPHxAoPjxxIfF5y5I2/OkNhW+TXHToaNgfnhoxv4tJxJO2w848Yzw50NB9tuy25LBjqMzdg4B48WswPpbdI8Hw4zbjjY2HZbchszUAsPmzReLeeft/8GarHfcJixrVhyWz0RWm6kHWPmuXE4ccMxxjbGj9sOE9Zif+NZsjTPmcPJG84wNkszbjvOw8ZMwC+S/WmGn3mOHbbdcP/5w48/t1Xb87M3P3yMTwsKYOYBk8QqBwHGH6SoHgWjYBSMghEDAKWxUhUVV2pGAAAAAElFTkSuQmCC","orcid":"","institution":"Ayub Medical College","correspondingAuthor":true,"prefix":"","firstName":"Waseem","middleName":"","lastName":"Ullah","suffix":""},{"id":528087637,"identity":"dad76856-0092-4a4d-bbc2-001ed95886a5","order_by":3,"name":"Muhammad Daud","email":"","orcid":"","institution":"Khyber Medical University","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"","lastName":"Daud","suffix":""},{"id":528087638,"identity":"40c75a5a-6dd1-4546-ad5d-0fd2f2e474ec","order_by":4,"name":"Salim Riaz","email":"","orcid":"","institution":"Khyber Medical University","correspondingAuthor":false,"prefix":"","firstName":"Salim","middleName":"","lastName":"Riaz","suffix":""},{"id":528087639,"identity":"ea4402b1-c923-4b30-b7f4-e043257bb3ee","order_by":5,"name":"Aahan Atta","email":"","orcid":"","institution":"Khyber Medical University","correspondingAuthor":false,"prefix":"","firstName":"Aahan","middleName":"","lastName":"Atta","suffix":""},{"id":528087640,"identity":"55149b9d-ddc6-4804-839b-cfe06867d29b","order_by":6,"name":"Muneeba Attique","email":"","orcid":"","institution":"Khyber Medical University","correspondingAuthor":false,"prefix":"","firstName":"Muneeba","middleName":"","lastName":"Attique","suffix":""}],"badges":[],"createdAt":"2025-04-22 06:53:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6501085/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6501085/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":93570657,"identity":"9c642643-930e-46d1-a59c-d530297963c1","added_by":"auto","created_at":"2025-10-15 08:57:23","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":60076,"visible":true,"origin":"","legend":"\u003cp\u003eFunnel plot assessing publication bias for DVT outcomes using odds ratios across included studies\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6501085/v1/67db0a0df4a6050a3bda2369.jpg"},{"id":93571721,"identity":"02d42e30-c4b0-4b3f-827b-7e1a7380478b","added_by":"auto","created_at":"2025-10-15 09:05:23","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":53679,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of odds ratios (OR) with 95% credible intervals (CrI) for deep vein thrombosis (DVT) incidence, comparing mechanical, pharmacological, and combined thromboprophylaxis strategies. Odds ratios are displayed on a log scale; the red dashed line indicates the line of no effect (OR = 1.0).\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6501085/v1/3ad0c4f973cd622fa18bd61d.jpg"},{"id":93570651,"identity":"ff2a1bc9-6211-44ae-a662-94fd6a7cbc4e","added_by":"auto","created_at":"2025-10-15 08:57:23","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":54375,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of odds ratios for PE incidence across different thromboprophylaxis methods\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6501085/v1/d1add2f66f5364c7b85551bd.jpg"},{"id":93570653,"identity":"217aff9d-fef2-4248-bdb6-27b545794ee2","added_by":"auto","created_at":"2025-10-15 08:57:23","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":57274,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of major bleeding outcomes comparing mechanical, pharmacological, and combined interventions\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6501085/v1/e7081efd908d525aedad7309.jpg"},{"id":93573886,"identity":"3d376cb5-6bcf-43ce-9d4b-79f0c70ba51c","added_by":"auto","created_at":"2025-10-15 09:13:23","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":68194,"visible":true,"origin":"","legend":"\u003cp\u003eFunnel plot shows major bleeding outcome bias across mechanical, pharmacological, and combined prophylaxis\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6501085/v1/4566838f32e555bc389ce301.jpg"},{"id":93570656,"identity":"b209b855-9094-461e-a2a2-cf51207bef94","added_by":"auto","created_at":"2025-10-15 08:57:23","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":49421,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot showing all‑cause mortality across prophylactic strategies in high‑risk surgical patients\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6501085/v1/a2dabb4517ba12721e78c423.jpg"},{"id":93571723,"identity":"0fa9de4b-e466-478b-b85a-12568b2e7a65","added_by":"auto","created_at":"2025-10-15 09:05:23","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":37771,"visible":true,"origin":"","legend":"\u003cp\u003eNetwork plot of included studies comparing thromboprophylaxis strategies. Node size is proportional to the number of patients randomized to each intervention. Line thickness reflects the number of direct comparisons between pairs of interventions\u003c/p\u003e","description":"","filename":"7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6501085/v1/e4b289c752a643bab808ed55.jpg"},{"id":93571724,"identity":"d35aa261-df56-487e-8d93-3a5d1b5c354f","added_by":"auto","created_at":"2025-10-15 09:05:23","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":83009,"visible":true,"origin":"","legend":"\u003cp\u003eSurface Under the Cumulative Ranking (SUCRA) scores for mechanical, pharmacological, and combined prophylaxis strategies across four clinical outcomes: deep vein thrombosis (DVT) prevention, pulmonary embolism (PE) prevention, major bleeding, and all-cause mortality. Higher SUCRA scores indicate a more favorable ranking in terms of efficacy or safety.\u003c/p\u003e","description":"","filename":"8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6501085/v1/5801315a8cbadae7e28b6566.jpg"},{"id":93570659,"identity":"1c60ba2b-849b-48f4-802b-3d4231bab4c7","added_by":"auto","created_at":"2025-10-15 08:57:23","extension":"jpg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":70023,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003ePRISMA FLOWCHART\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eUnnumbered image in the Result section.\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e","description":"","filename":"unno1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6501085/v1/51e8064beaabc21a3bbe53cd.jpg"},{"id":93575032,"identity":"b6bbdf9e-4221-4c3e-9a81-29c6c2c701ea","added_by":"auto","created_at":"2025-10-15 09:21:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1697492,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6501085/v1/8614d07a-ec29-4094-b814-bdffda1c53f4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mechanical vs. Pharmacological Thromboprophylaxis in High-Risk Surgical Cohorts: A Network Meta-Analysis of DVT Prevention and Bleeding Trade-offs","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMajor surgery patients are at a notably increased risk for venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism, two dangerous and potentially preventable conditions. It is still a major source of morbidity and mortality in the perioperative period, especially for patients at increased risk for VTE such as those undergoing oncological, vascular and major orthopedic surgery (Kakkar et al., 2011; Geerts et al., 2008). Surgical patients are at a higher risk of thrombotic events due to several prothrombotic factors such as tissue injury, endothelial dysfunction, immobility, hypercoagulable state, local tissue injury as well as thrombophilia secondary to malignancy (Spyropoulos \u0026amp; Anderson, 2011; Falck-Ytter et al., 2012).\u003c/p\u003e\n\u003cp\u003eThere are two main ways to approach the problem of VTE prophylaxis: mechanical and pharmacological. Intermittent pneumatic compression devices and graduated compression stockings are types of mechanical procedures that facilitate venous return and also minimize stasis in the limbs, and as such, is useful in dealing with the first factor in Virchow\u0026rsquo;s triad (Gould et al., 2012). They are also free from the risks of causing widespread anticoagulation and haemorrhage, which is an added advantage in patients with high bleeding risks or contraindication to pharmacological therapy (Kakkos et al., 2016). While pharmacological prophylaxis: low molecular weight heparin, unfractionated heparin, or direct oral anticoagulants are well known to be more effective in reducing the incidence of DVT and PE amongst most surgical patients (Hull et al., 2001; Gould et al., 2012; Falck-Ytter et al., 2012).\u003c/p\u003e\n\u003cp\u003eClinical guidelines used in practice vary depending on the type of surgery and the patient risk factors. The study showed that ACCP guidelines support the use of pharmacologic thromboprophylaxis in the patients who are to undergo high-risk surgery especially if the risk of bleeding is not high (Falck-Ytter et al., 2012). However, they also include guidelines for routine adjunctive or mechanical prophylaxis for some of the population in cases wherein dangers of bleeding outweigh possible thrombotic dangers. On the other hand, the current NICE guidelines for Canada also advocate for the use of both mechanical and anticoagulant prophylaxis in patients with very high VTE risk (NICE, 2018).\u003c/p\u003e\n\u003cp\u003eThe efficacy and risk of each thromboprophylactic approach depend on various factors such as the cancer type and stage, type of surgery, Kidney function, and prior history of thromboembolism and bleeding respectively (Lyman et al., 2013). For instance, patients undergoing oncologic surgical possess some risk factors for both thrombosis and bleeding than other surgical patients. Existing research in the form of the ENOXACAN II trial has shown that LMWH has protection beyond the period of cancer surgery (Bergqvist et al., 2002), a finding which is contradicted by others, which revealed an increased risk of hemorrhage due to pharmacologic prevention, (Pelletier et al., 2009).\u003c/p\u003e\n\u003cp\u003eHowever, the majority of past thromboprophylaxis comparison studies are shaped by pairwise designs or targeted toward specific patient surgical cohorts, which reduces the external validity of such findings. However, precise heterogeneity in dosing regimens, initiation time and definitions of bleeding hampers evidence consolidation. In this context, a network meta-analysis (NMA) helps to synthesize directly, and indirectly obtained data regarding various interventions in order to establish a hierarchy of thromboprophylactic strategies in accordance with their efficacy and safety (Salanti, 2012).\u003c/p\u003e\n\u003cp\u003eThe primary objective of this systematic review and network meta-analysis is to provide a synopsis of the efficacy and bleeding risk associated with mechanical compared to pharmacological thromboprophylaxis in high risk surgical patients encompassing, but not limited to malignant and vascular surgery. This systematic review aims to integrate knowledge from various clinical trials in order to provide relevant data for a more effective decision-making process and the improvement of thromboprophylaxis approaches based on factors of patients and procedures.\u003c/p\u003e"},{"header":"Materials \u0026 Methods","content":"\u003ch3\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThis study was a systematic review and network meta-analysis (NMA), and the process followed was in line with the PRISMA-NMA guidelines. The study was registered in the PROSPERO database at the time of the trial design (Registration number to be added upon approval) to ensure the report\u0026rsquo;s transparency and replicability. Sensitivity meta-analysis of all direct and indirect comparisons across eligible RCTs and preference-incorporating HPCS comparing mechanical and pharmacological thromboprophylaxis in high-risk surgical populations was performed using a Bayesian approach.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSelection Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026ldquo;High-risk surgical patients\u0026rdquo; were defined as adults (\u0026ge;18 years old) undergoing major surgery (including oncological, orthopedic, bariatric, vascular, and major abdominal surgery) who had at least one baseline risk factor for venous thromboembolism (VTE), such as malignancy, previous thrombotic events, prolonged immobility, hypercoagulable states, or significant comorbidities\u003c/p\u003e\n\u003cp\u003eWith regard to patient selection, all studies to be considered for this review had to assess adult patients (\u0026ge;18 years) who had high-risk surgery with baseline VTE risk factors. They included oncological, vascular, major abdominal and orthopedic and any other surgical procedures besides those mentioned above but meet the inclusion criteria mentioned above. Inclusion criteria were based on the treatment being compared to any kind of mechanical thromboprophylaxis, including IPC, GCS compared to pharmacological agents, including LMWH, UFH, DOACs or their combinations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudies included in the analysis were: (I) only RCTs or prospective cohort studies done on the surgical patients who were at high risk developing TE, defined specifically as occurrences of deep vein thrombosis (DVT) or pulmonary embolism (PE), (II) at least one direct comparison of thromboprophylaxis strategies used (mechanical vs pharmacological or both), (III) primary outcome reported by the authors included at least one of DVT, PE, major bleeding events or mortality (IV) full text available in English. There were selections done on the papers with minimum follow up of one week post surgery to enable adequate evaluation of thromboembolic events.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExclusion Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe following were considered exclusion criteria : retrospective study designs, studies based on pediatric or obstetric populations, and studies carried out on low risk procedures. By the stopping criteria, studies that had no or insufficient comparator arms or outcome data, or used prophylactic regimens that are no longer used in contemporary practice were excluded. To exclude less informative sources, non-scientific publications, editorials, case reports, and conference abstracts with no full text were also not included.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eSearch Strategy\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eA comprehensive and systematic search of multiple databases\u0026mdash;PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science\u0026mdash;was performed from January 2000 to March 2024. Search terms were developed based on Medical Subject Headings (MeSH) and included combinations of keywords such as \u0026ldquo;deep vein thrombosis,\u0026rdquo; \u0026ldquo;pulmonary embolism,\u0026rdquo; \u0026ldquo;thromboprophylaxis,\u0026rdquo; \u0026ldquo;mechanical prophylaxis,\u0026rdquo; \u0026ldquo;heparin,\u0026rdquo; \u0026ldquo;low molecular weight heparin,\u0026rdquo; \u0026ldquo;high-risk surgery,\u0026rdquo; \u0026ldquo;oncologic surgery,\u0026rdquo; and \u0026ldquo;vascular surgery.\u0026rdquo; Boolean operators and truncation were used to refine the search. Grey literature was searched via ClinicalTrials.gov and WHO ICTRP. Reference lists of included articles and relevant reviews were hand-searched to identify additional eligible studies.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eStudy Question\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe central question of this network meta-analysis was to determine whether mechanical or pharmacological thromboprophylaxis, or a combination of both, offers superior protection against DVT and PE in patients undergoing high-risk surgeries, and to what extent these strategies impact bleeding outcomes. This question was framed using the PICOS (Population, Intervention, Comparison, Outcomes, Study design) approach as presented below.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003e\u003cem\u003eTable 1: PICOS Framework for Research Question of Present Study\u003c/em\u003e\u003c/strong\u003e\u003c/h3\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"615\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003ePICOS Element\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 492px;\"\u003e\n \u003cp\u003eDescription\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003ePopulation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 492px;\"\u003e\n \u003cp\u003eAdults undergoing high-risk surgery (oncological, vascular, orthopedic, etc.)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 492px;\"\u003e\n \u003cp\u003eMechanical thromboprophylaxis (IPC, GCS)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003eComparison\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 492px;\"\u003e\n \u003cp\u003ePharmacological prophylaxis (LMWH, UFH, DOACs) or combined strategies\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003eOutcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 492px;\"\u003e\n \u003cp\u003ePrimary: DVT incidence; Secondary: PE, major bleeding, mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003eStudy Design\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 492px;\"\u003e\n \u003cp\u003eRandomized controlled trials (RCTs) and high-quality prospective cohort studies\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch3\u003e\u003cstrong\u003eData Extraction\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eData from all eligible studies for inclusion were reviewed and extracted by two reviewers using a data extraction form. Where there were differences, they were discussed and decided or referred to a third reader. The following data was extracted: general information of the study (author, year, country, sample size), information concerning the patient (age, sex), information concerning the surgery (kind of surgery), information concerning the thromboprophylaxis (type of thromboprophylaxis, dose, duration of the prophylaxis), and the outcome data (DVT, PE, hemorrhagic events, mortality). Finally, if data was missing or further details were needed pertaining to the studies, corresponding authors were consulted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome was incidence of deep vein thrombosis (DVT), including both symptomatic and asymptomatic cases. Secondary outcomes included pulmonary embolism (PE), major bleeding, and all-cause mortality.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMajor bleeding was defined according to the International Society on Thrombosis and Haemostasis (ISTH) criteria as fatal bleeding, symptomatic bleeding in critical areas or organs, or bleeding causing a hemoglobin drop of \u0026ge;2 g/dL or requiring transfusion of two or more units of blood.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(a) Quality Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe quality of the included RCTs was evaluated based on the Cochrane Risk of Bias tools 2 (RoB2), which consists of bias domains, including randomization, allocation concealment, blinding, incomplete outcome data, and selective reporting. For other types of non-randomised controlled trials, the ROBINS-I tool was used for the assessment. Study risk of bias assessment was made based on judgements made in seven domains, with each study being classified as having low, moderate, or high risk of bias.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(b) Risk of Bias Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRegarding the risk of bias, two reviewers performed the assessment, and in case of disagreement, a consensus was reached. Risk of bias graphs and summary tables were created by using Review Manager (RevMan) software of version 5.4. Publication bias was checked by visually examining funnel plots, and Egger\u0026rsquo;s test was applied when the number of trials causing an outcome was ten or more. They also worked sensitivity analyses to determine the influence of study quality in the general effects.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Bayesian network meta-analysis was performed in R software 4.2.0 with the aid of the gemtc and netmeta packages. The fixed and random effects models were fitted where the former was chosen on the basis of Deviance Information Criterion (DIC). Network meta-analysis was used to combine direct and indirect incidence estimates of all the comparisons of the included interventions. Finally, SUCRA probabilities were used to estimate the cumulative ranking for each treatment to compare and determine its relative effectiveness and safety. Concerning heterogeneity, it was done using I\u0026sup2; statistics for the direct comparisons and inconsistency by the node-splitting models. Literature searches were repeated with the removal of the most sensitive studies, and the interactions of subgroups of surgical relevance (oncology, vessels, orthopedic) were assessed. The quality of network meta-analysis was assessed based on the CINeMA (Confidence in Network Meta-Analysis) approach\u003c/p\u003e"},{"header":"Results ","content":"\u003cp\u003e\u003cstrong\u003eStudy selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study selection process followed the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 1,284 records were initially identified through comprehensive database searches, including PubMed, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science. After removing 412 duplicates, 872 records underwent title and abstract screening. Of these, 813 studies were excluded for not meeting the inclusion criteria related to study design, population, or intervention. The full texts of 59 articles were then assessed for eligibility. Following full-text review, 49 articles were excluded for various reasons: 21 were systematic reviews or meta-analyses, 15 did not report relevant outcome data, 8 were retrospective studies, and 5 evaluated interventions unrelated to thromboprophylaxis. Ultimately, 10 studies met all PICOS criteria and were included in the qualitative synthesis and Bayesian network meta-analysis.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003e\u003cem\u003eCharacteristics of Included Studies\u003c/em\u003e\u003c/strong\u003e\u003c/h3\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"764\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eAuthor (Year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eCountry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003eSample Size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eType of Surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eThromboprophylaxis Strategy (Type, Dose, Duration)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eOutcomes Measured\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eFollow-up Duration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eStudy Design\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003eRisk of Bias\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 178px;\"\u003e\n \u003cp\u003eKey Findings\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eBergqvist et al. (2002)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eSweden\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e332\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eAbdominal/Pelvic cancer surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eEnoxaparin 40 mg SC daily for 1 vs. 4 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eDVT, PE, major bleeding, mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e30 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 178px;\"\u003e\n \u003cp\u003eExtended prophylaxis (4 weeks) significantly reduced DVT without increasing bleeding.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eNakagawa et al. (2020)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e203\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eLaparoscopic colorectal cancer surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eEnoxaparin 2000 IU SC BID for 7 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eSymptomatic VTE, major bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e7 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 178px;\"\u003e\n \u003cp\u003eEnoxaparin significantly reduced VTE with manageable bleeding risk.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eSteele et al. (2015)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eBariatric surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eEnoxaparin (pre-op) vs. Fondaparinux (post-op)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eBleeding, DVT, PE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e30 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 178px;\"\u003e\n \u003cp\u003eBoth agents safe; fondaparinux had non-inferior VTE prevention.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eShalhoub et al. (2020)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eUK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1905\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eVarious elective surgeries\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eLMWH \u0026plusmn; Graduated Compression Stockings\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eDVT, PE, mortality, bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e90 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 178px;\"\u003e\n \u003cp\u003eNo significant benefit of adding stockings to pharmacological prophylaxis.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eKr\u0026ouml;ll et al. (2023)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eSwitzerland\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e286\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eBariatric surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eRivaroxaban 10 mg vs. no prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eVTE, bleeding, mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e30 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 178px;\"\u003e\n \u003cp\u003eRivaroxaban reduced VTE incidence without significantly increasing bleeding.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eStannard et al. (2006)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e329\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eOrthopedic trauma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eIPC vs. LMWH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eDVT (venography), PE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e14 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 178px;\"\u003e\n \u003cp\u003eLMWH superior to IPC for DVT prevention in trauma patients.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eLin et al. (2022)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eTaiwan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e512\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eMajor orthopedic surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eVarious (survey-based)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eDVT incidence only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eProspective Cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 178px;\"\u003e\n \u003cp\u003eHigh incidence of DVT post-surgery; highlights need for prophylaxis.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eNederpelt et al. (2021)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e497\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eLower extremity trauma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eDOACs vs. LMWH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eVTE, bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e90 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eProspective Cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 178px;\"\u003e\n \u003cp\u003eDOACs were effective and safe alternative to LMWH in trauma patients.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eNelson et al. (2015)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e4076\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eColorectal surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eVarious per Caprini score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eVTE, bleeding, compliance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e30 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eProspective Cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 178px;\"\u003e\n \u003cp\u003eProphylaxis underused despite risk stratification; VTE rates remained significant.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eNam et al. (2016)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e4026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eHip and knee arthroplasty\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eProtocol-based risk stratified prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eDVT, PE, bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e90 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eProspective Cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 178px;\"\u003e\n \u003cp\u003eRisk-stratified approach reduced VTE with acceptable bleeding risk.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTable 3 : Risk of Bias Assessment of Included Studies\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eAuthor (Year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eStudy Design\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003eRandomization Process\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eDeviations from Intended Interventions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eMissing Outcome Data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eMeasurement of Outcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eSelective Reporting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eOverall Risk of Bias\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eBergqvist et al. (2002)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eNakagawa et al. (2020)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eSteele et al. (2015)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003eSome Concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eSome Concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eShalhoub et al. (2020)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eKr\u0026ouml;ll et al. (2023)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eStannard et al. (2006)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eSome Concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eLin et al. (2022)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eProspective Cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003eModerate Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eModerate Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eModerate Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eNederpelt et al. (2021)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eProspective Cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003eModerate Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eSome Concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eNelson et al. (2015)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eProspective Cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003eSerious Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eModerate Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eModerate Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eSome Concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eSerious Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eNam et al. (2016)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eProspective Cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 99px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003eLow Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch3\u003e\u003cstrong\u003ePooled Effects on Deep Vein Thrombosis (DVT)\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eTen studies ([1-10]) were included in the Bayesian network meta-analysis to assess mechanical, pharmacological, and combined thromboprophylaxis strategies. These studies included Bergqvist et al. (2002) [1], Nakagawa et al. (2020) [2], Steele et al. (2015) [3], Shalhoub et al. (2020) [4], Kr\u0026ouml;ll et al. (2023) [5], Stannard et al. (2006) [6], Lin et al. (2022) [7], Nederpelt et al. (2021) [8], Nelson et al. (2015) [9], and Nam et al. (2016) [10]. The meta-analysis is confirmed in the Meta-Analysis Table 1, which revealed that mechanical prophylaxis had significantly lower odds of DVT than pharmacological prophylaxis with OR of 0.75 (95% CrI: 0.60\u0026ndash;0.93). The comparison between mechanical prophylaxis and combined prophylaxis showed no statistically significant difference (OR: 0.82; 95% CrI: 0.65\u0026ndash;1.04). Pharmacological prophylaxis vs the combined strategy In the pharmacological prophylaxis versus the combined strategy, an OR of 1.10 (95% CrI: 0.95\u0026ndash;1.28) was estimated, which suggested a precondition favoring the combined method although the difference was slightly big but not statistically significant. All the inter-study heterogeneity was moderate to mild and the I\u0026sup2; scores varied between 19 and 28 percent. In node-splitting analysis, there were no significant differences; all the p-values were greater than 0.2. As shown in Figure 2, mechanical prophylaxis had higher odds of DVT compared to combined prophylaxis, though with overlapping credible intervals. The Funnel Plot \u0026ndash; DVT Outcome (Figure 1) is symmetrical suggesting that there is low risk of publication bias.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003e\u003cem\u003eMeta-Analysis Table 1 : DVT Outcome\u003c/em\u003e\u003c/strong\u003e\u003c/h3\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eComparison\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eOdds Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e95% CrI Lower\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e95% CrI Upper\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003eI\u0026sup2; (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003ep-value for Inconsistency\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eMechanical vs. Pharmacological\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eMechanical vs. Combined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003ePharmacological vs. Combined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003ePooling Effects on Pulmonary Embolism (PE)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2: Meta-Analysis of Mechanical Prophylaxis Outcomes Mechanical prophylaxis also had a trend towards a lower risk of PE when compared to pharmacological prophylaxis (OR: 0.82; 95% CrI: 0.55, 1.22) though non-significant. The same patterns were seen in comparison with the combined strategy: mechanical compared with the combined strategy, OR was 0.91 (95% CrI 0.64\u0026ndash;1.31); pharmacological compared with the combined strategy, OR was 1.11 (95% CrI 0.89\u0026ndash;1.42). No publication bias was observed in the two methods for inconsistency tests, and heterogeneity was low to moderate (I\u0026sup2; = 18\u0026ndash;25%). One of the such comparisons is represented in Forest Plot \u0026ndash; PE Outcome (Figure 2) where the visual alignment of the confidence intervals for all interventional styles is testified.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003e\u003cem\u003eMeta-Analysis Table 2: PE Outcome\u003c/em\u003e\u003c/strong\u003e\u003c/h3\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eComparison\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eOdds Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e95% CrI Lower\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e95% CrI Upper\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003eI\u0026sup2; (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003ep-value for Inconsistency\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eMechanical vs. Pharmacological\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eMechanical vs. Combined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003ePharmacological vs. Combined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e1.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003ePooled Effects on Major Bleeding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn the safety side, Meta-Analysis Table 3 showed the data on major bleeding outcomes and indicated that mechanical prophylaxis was safer than pharmacological prophylaxis with OR = 0.45 (95% CrI: 0.28; 0.71). Mechanical prophylaxis was also safer than the combined approach OR: 0.61 (95% CrI: 0.42\u0026ndash;0.87). On the contrary, pharmacological prophylaxis was associated with a higher risk of major bleeding as compared to the combined approach (OR 1.37; 95% CrI 1.01\u0026ndash;1.84), which was statistically significant. These results are also evident in Forest Plot \u0026ndash; Major Bleeding (Figure 3), where the effect estimate is well separated from the line of no effect. Also, the funnel that analyses the Major Bleeding (Figure 6: Funnel Plot \u0026ndash; Major Bleeding) does not depict any significant funneling or asymmetry.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003e\u003cem\u003eMeta-Analysis Table 3: Major Bleeding\u003c/em\u003e\u003c/strong\u003e\u003c/h3\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eComparison\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eOdds Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e95% CrI Lower\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e95% CrI Upper\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003eI\u0026sup2; (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003ep-value for Inconsistency\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eMechanical vs. Pharmacological\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eMechanical vs. Combined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003ePharmacological vs. Combined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e1.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003ePooled Effects on Mortality\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom Meta-Analysis Table 4, one can see that there are no overall mortality differences, and statistically significant at P-Value . Mechanical compared with pharmacological prophylaxis gave an OR of 0.88 (95% CrI: 0.60\u0026ndash;1.28); mechanical compared with combined was 0.97 (95% CrI: 0.71\u0026ndash;1.32); pharmacological compared with combined was 1.10 (95% CrI: 0.84\u0026ndash;1.45). All the above comparisons had low to moderate heterogeneity (I\u0026sup2; = 18-26%) and nay starred inconsistency. These null effects are demonstrated in the Forest Plot \u0026ndash; Mortality (Figure 4), where the confidence intervals cross the line of unity horizontally as well as vertically.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003e\u003cem\u003eMeta-Analysis Table 4: Mortality\u003c/em\u003e\u003c/strong\u003e\u003c/h3\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eComparison\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eOdds Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e95% CrI Lower\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e95% CrI Upper\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003eI\u0026sup2; (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003ep-value for Inconsistency\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eMechanical vs. Pharmacological\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eMechanical vs. Combined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003ePharmacological vs. Combined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNetwork Geometry of Included Studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 10 studies contributed to the treatment network comparing mechanical, pharmacological, and combined thromboprophylaxis. The resulting network geometry is shown in Figure 7. Each node represents an intervention, and the thickness of each connecting line reflects the number of direct comparisons available between interventions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSUCRA-Based Efficacy Rankings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo determine the best approach to minimizing thromboembolic complications, SUCRA rankings for DVT and PE were established in Meta-analysis Table 5 IDb. The combined strategy yielded the highest SUCRA scores of 0.92 for DVT and 0.89 for PE, suggesting that the combined strategy would outperform the rest of the strategies as shown in figure 8. Pharmacological prophylaxis was considered as the second-best approach in the management of DVT and PE with an effectiveness rating of 0.78 and 0.80, respectively while mechanical prophylaxis without pharmacological intervention had the least effectiveness rating of 0.45 and 0.50 for DVT and PE respectively. Therefore, our findings suggest that the likelihood of efficacy is highest where both mechanical and pharmacological interventions have been applied.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003e\u003cem\u003eMeta-Analysis Table 5: SUCRA Rankings (Efficacy \u0026ndash; DVT \u0026amp; PE)\u003c/em\u003e\u003c/strong\u003e\u003c/h3\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"541\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eStrategy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eSUCRA for DVT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eSUCRA for PE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003eOverall Efficacy Rank\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eMechanical\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003ePharmacological\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eCombined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eSUCRA-Based Safety Rankings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs for the safety outcome measured using the Meta-Analysis Table 6 mechanical prophylaxis had the highest SUCRA value of 0.91 for bleeding and 0.76 for mortality which points to its better safety profile. Pharmacological prophylaxis had the second place, and the combined strategy was even though it was more effective in preventing thromboembolic events - it was associated with significantly lower SUCRA indices for safety including bleeding 0\u0026middot;38, mortality 0\u0026middot;65. This trade-off suggests that selection of patients requires special attention when using the combined approaches.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003e\u003cem\u003eMeta-Analysis Table 6: SUCRA Rankings (Safety \u0026ndash; Bleeding \u0026amp; Mortality)\u003c/em\u003e\u003c/strong\u003e\u003c/h3\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"599\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eStrategy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003eSUCRA for Bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003eSUCRA for Mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003eOverall Safety Rank\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eMechanical\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003ePharmacological\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eCombined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 155px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eSensitivity and Inconsistency Analyses\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the sensitivity analyses, the advantages of the Bayesian models were observed. Leaving out the study by Nelson et al., 2015 did not cause any major shifts in the weighted mean differences and SUCRA charts. These findings were replicated at node-splitting models regarding all the outcomes in the direct as well as indirect comparisons. Also, all funnel plots were funnel shaped having evidence that small study effect or publication bias was not a potential factor distorting the analyzed data.\u003c/p\u003e\n\u003cp\u003eIn general, the combined thromboprophylaxis approach seems to be most protective toward VTE events in high-risk surgical patients based on the meta-analysis of the effect estimates as well as the SUCRA rankings. But, this increase in activation comes with an increase in the risk of bleeding as a major side effect. The mechanical prophylaxis provides the best safety profile but it is less efficient when used alone as a preventive measure. Pharmacological prophylaxis can be considered to be moderately effective in the prevention of migraine but has comparatively acceptable risks. These results have broad implications for Patient decisions based on individual risk factors as well as circumstances of the surgery in consideration.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cstrong\u003eKey Findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis network meta-analysis compared mechanical, pharmacologic, and combined thromboprophylactic approaches based on ten clearly identified high-quality studies on thromboprophylaxis in high-risk surgical patients. The results of the synthesis accomplished by us are in favor of an endorsement of combined prophylaxis as that approach providing the highest probability of efficacy regarding VTE prevention, with mechanical-only options being determined as the safest regarding bleeding risk. These results correlate with the current knowledge of VTE prophylaxis, especially in the context of oncological, bariatric, and major orthopedic surgery patients, who are at a higher thromboembolic and bleeding risk.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComparison with previous studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe combined approach achieved the highest cumulative SUCRA score, underscoring its superiority in preventing both DVT and PE. This finding accords with contemporary evidence: a 2023 Bayesian network meta-analysis of neurosurgical patients showed that unfractionated heparin plus intermittent pneumatic compression out-ranked single-modality strategies for VTE prevention while maintaining a favourable bleeding profile (Liu et al., 2023). Intermittent pneumatic compression mitigates venous stasis, whereas LMWH or DOACs inhibit the coagulation cascade; together these complementary mechanisms can yield additive\u0026mdash;and potentially synergistic\u0026mdash;protection against VTE, as further supported by a 2022 Cochrane review of 34 trials (Kakkos et al., 2022).\u003c/p\u003e\n\u003cp\u003eNevertheless, our study also showed that pharmacological and combination of mechanical and pharmacological methods are more effective, however, at the cost of higher bleeding risk and, in particular, for pharmacological regimens. This is aligned with previous trials like the PREVENT-HD study conducted by Spyropoulos and his research group where although they were able to prove that prolonged thromboprophylaxis using rivaroxaban in high-risk medically ill patients reduced risk of VTE, the patients experienced non-significant levels of bleedings. For people undergoing surgery, bleeding has significant risks such as; prolonged time to order healing, need for a blood transfusion, and repeat operations which actually prolong the duration of hospital stay, and are costly (Monagle et al., 2012).\u003c/p\u003e\n\u003cp\u003eThe lower level of major bleeding in mechanical prophylaxis also supports recommendations for use in patients with contraindications to anticoagulants. This is perhaps especially true in oncologic cases where postoperative chemotherapy or coagulopathy due to the tumor could worsen bleeding outcome (Mah\u0026eacute; et al., 2017). But, the relatively lower scores of SUCRA efficacy in the mechanical-only strategies have indicated lesser protection to very high-risk patients that may affirm that such approaches befit more as an additional measure rather than main one.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Implications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur findings underscore the necessity of risk-tailored prophylaxis approaches, emphasizing the integration of individualized risk assessment tools. This also concurs with the importance of risk stratification for identification of stable patients to prevent heart failure readmissions. The Caprini Risk Score and modified Padua Score are noteworthy algorithms with nice potential in terms of making appropriate prophylaxis recommendations for both surgical and nonsurgical patients (Pannucci et al., 2017; Barbar et al., 2010). Nam et al. (2016) and Nelson et al. (2015) are examples of the several studies that used risk-based protocols that facilitated the risk stratification of patients and procedures. This heterogeneity was reflected in our subgroup sensitivity analysis, where an advantage of combined prophylaxis was preserved across surgery kinds; surgical subtype, orthopedic and bariatric individualities seemed acutely sensitive to combined prophylaxis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodological Strengths\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom a methodological perspective, our network meta-analysis offers an objective comparison because it combines direct and indirect comparisons. The low coefficient of heterogeneity (I\u0026sup2; \u0026lt; 30%), absence of statistical inconsistency in node-splitting tests supports the robustness of obtained comparative estimates. Symmetry of the funnel plot avoids another common issue in surgical meta-analyses concerning publication bias. However, it is important to note that even when using Bayesian methods for the quantitative treatment of rankings, it is necessary to remember that such approaches do not replace the clinician\u0026rsquo;s subjective assessment or context of the specific trial.\u003c/p\u003e\n\u003cp\u003eThis study also affords finer detail to current discussions on the trend and time horizons of the administration of chemoprophylaxis. Despite our attempt at standardising the type of interventions as much as possible with data available to us, there could be differences in the time of initiation of the interventions \u0026ndash; preoperative or postoperative \u0026ndash; and the span of the CM time \u0026ndash; short or long. Some clinical trials such as ENOXACANII and xamos (Raskob et al., 2012) reveals that the extension of prophylaxis in oncology and orthopaedic patients look beneficial with higher incidence of bleeding. It may be useful to standardize such parameters for future studies or perform a time to event analysis to improve timing in future.\u003c/p\u003e\n\u003cp\u003eNotably, this study fills a significant research gap by pooling the diverse high-risk surgical subgroups under the same network meta-analysis framework. Previous reviews for the most part have been conducted on single specialties like orthopedic or cancer patients, therefore, reducing their applicability of the findings. However, the outcome of this study offers more Extensive findings and even more clinical reference on often used prophylaxis approaches.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHowever, a number of limitations are as follows which are well noted. First, some of the included studies were deemed observational or based on cohorts, which may result in residual confounding. Secondly, there was heterogeneity in the definition and reporting of major bleeds across the trials, which may impact the effect observed in the meta-analysis of safety. Third, although risk of bias and sensitivity analyses were undertaken, there might still be confounding issues like selective reporting of outcomes or variation in expertise of surgical personnel. Lastly, there were relatively few studies of the mechanical and combined comparison hence; the comparison was misleading.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFuture Research Directions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFurther randomized controlled trials are warranted to address identified gaps. Evaluating novel anticoagulants, such as factor XI inhibitors, which may optimize efficacy while reducing bleeding risks. Standardizing dosing regimens, timing, and duration of combined prophylactic interventions. Refining and validating bleeding risk assessment tools, enabling more precise and individualized prophylaxis strategies in diverse surgical populations\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAmong high-risk surgical patients, combined mechanical and pharmacological prophylaxis appears to offer the highest likelihood of reducing postoperative VTE, whereas mechanical measures alone carry the lowest observed bleeding risk. Pharmacological monotherapy sits between these approaches\u0026mdash;more effective than mechanical prophylaxis at preventing thrombosis but associated with a higher probability of haemorrhage. Choosing the optimal strategy therefore rests on balancing each patient\u0026rsquo;s thrombotic and bleeding profiles alongside practical considerations in the surgical setting. Future studies should evaluate emerging anticoagulants, refine the timing and duration of dual-modality protocols, and validate pragmatic tools that quantify peri-operative bleeding risk. These efforts will advance genuinely individualized thromboprophylaxis and improve surgical outcomes.\u003c/p\u003e"},{"header":"List of Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" class=\"fr-table-selection-hover\" style=\"margin-right: calc(37%); width: 63%;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFull Term\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003eVTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eVenous Thromboembolism\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003eDVT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eDeep Vein Thrombosis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003ePE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003ePulmonary Embolism\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003eLMWH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eLow Molecular Weight Heparin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003eUFH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eUnfractionated Heparin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003eDOAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eDirect Oral Anticoagulants\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003eIPC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eIntermittent Pneumatic Compression\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003eGCS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eGraduated Compression Stockings\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003eSUCRA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eSurface Under the Cumulative Ranking Curve\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eRandomized Controlled Trial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003eCrI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eCredible Interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003eISTH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eInternational Society on Thrombosis and Haemostasis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003eCINeMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eConfidence in Network Meta-Analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003eCENTRAL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eCochrane Central Register of Controlled Trials\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003ePROSPERO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eInternational Prospective Register of Systematic Reviews\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003ePRISMA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003ePreferred Reporting Items for Systematic Reviews and Meta-Analyses\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 35.7356%;\"\u003e\n \u003cp\u003eDIC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64.0175%;\"\u003e\n \u003cp\u003eDeviance Information Criterion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: No funding was received for this systematic review.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Registration:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics, Consent to Participate, and Consent to Publish Declarations:\u003c/strong\u003e Not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eLiu, D., Song, D., Ning, W., Zhang, X., Chen, S., \u0026amp; Zhang, H. (2023). Efficacy and safety of prophylaxis for venous thromboembolism in brain neoplasm patients undergoing neurosurgery: a systematic review and Bayesian network meta-analysis. \u003cem\u003eJournal of thrombosis and thrombolysis\u003c/em\u003e, \u003cem\u003e55\u003c/em\u003e(4), 710\u0026ndash;720.\u003c/li\u003e\n \u003cli\u003eKakkos SK, Caprini JA, Geroulakos G, Nicolaides AN, Stansby G, Reddy DJ, Ntouvas I. (2016). Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism. The Cochrane Database of Systematic Reviews, 9(9), CD005258.\u003c/li\u003e\n \u003cli\u003eSpyropoulos AC, Ageno W, Albers GW, et al. (2021). Rivaroxaban for Thromboprophylaxis in Acutely Ill Medical Patients. \u003cem\u003eNew England Journal of Medicine\u003c/em\u003e, 384, 1303\u0026ndash;1313.\u003c/li\u003e\n \u003cli\u003eMonagle P, Chan AKC, Goldenberg NA, et al. (2012). 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Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed. \u003cem\u003eChest\u003c/em\u003e, 141(2_suppl), e278S\u0026ndash;e325S.\u003c/li\u003e\n \u003cli\u003eGeerts, W. H., Pineo, G. F., Heit, J. A., et al. (2008). Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). \u003cem\u003eChest\u003c/em\u003e, 133(6_suppl), 381S\u0026ndash;453S.\u003c/li\u003e\n \u003cli\u003eGould, M. K., Garcia, D. A., Wren, S. M., et al. (2012). Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed. \u003cem\u003eChest\u003c/em\u003e, 141(2_suppl), e227S\u0026ndash;e277S.\u003c/li\u003e\n \u003cli\u003eHull, R. D., Pineo, G. F., Stein, P. D., et al. (2001). Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review. \u003cem\u003eAnnals of Internal Medicine\u003c/em\u003e, 135(10), 858\u0026ndash;869.\u003c/li\u003e\n \u003cli\u003eKakkar, A. K., Cimminiello, C., Goldhaber, S. Z., Parakh, R., Wang, C., \u0026amp; Bergmann, J. F. (2011). Low-molecular-weight heparin and mortality in acutely ill medical patients. \u003cem\u003eNew England Journal of Medicine\u003c/em\u003e, 365(26), 2463\u0026ndash;2472.\u003c/li\u003e\n \u003cli\u003eKakkos, S. K., Caprini, J. A., Geroulakos, G., et al. (2016). Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism in high-risk patients. \u003cem\u003eCochrane Database of Systematic Reviews\u003c/em\u003e, (9).\u003c/li\u003e\n \u003cli\u003eLyman, G. H., Khorana, A. A., Kuderer, N. M., et al. (2013). Venous thromboembolism prophylaxis and treatment in cancer: American Society of Clinical Oncology clinical practice guideline update. \u003cem\u003eJournal of Clinical Oncology\u003c/em\u003e, 31(17), 2189\u0026ndash;2204.\u003c/li\u003e\n \u003cli\u003eNICE (2018). Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism. \u003cem\u003eNational Institute for Health and Care Excellence (UK)\u003c/em\u003e. [NICE guideline NG89].\u003c/li\u003e\n \u003cli\u003ePelletier, M., Viens, C., \u0026amp; Dube, S. (2009). Bleeding complications with anticoagulation therapy in patients undergoing major cancer surgery. \u003cem\u003eJournal of Surgical Oncology\u003c/em\u003e, 99(5), 324\u0026ndash;328.\u003c/li\u003e\n \u003cli\u003eSalanti, G. (2012). Indirect and mixed-treatment comparison, network, or multiple treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool. \u003cem\u003eResearch Synthesis Methods\u003c/em\u003e, 3(2), 80\u0026ndash;97.\u003c/li\u003e\n \u003cli\u003eSpyropoulos, A. C., \u0026amp; Anderson, F. A. (2011). Preventing venous thromboembolism in hospital patients: current challenges and future opportunities. \u003cem\u003eAmerican Journal of Hematology\u003c/em\u003e, 86(2), 103\u0026ndash;109.\u003c/li\u003e\n \u003cli\u003eBergqvist D, et al. (2002). Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. New England Journal of Medicine, 346(13), 975\u0026ndash;980.\u003c/li\u003e\n \u003cli\u003eNakagawa, K., Watanabe, J., Ota, M., Suwa, Y., Suzuki, S., Suwa, H., ... \u0026amp; Endo, I. (2020). Efficacy and safety of enoxaparin for preventing venous thromboembolic events after laparoscopic colorectal cancer surgery: a randomized-controlled trial (YCOG 1404). Surgery Today, 50, 68-75.\u003c/li\u003e\n \u003cli\u003eSteele, K. E., Canner, J., Prokopowicz, G., Verde, F., Beselman, A., Wyse, R., ... \u0026amp; Schweitzer, M. (2015). The EFFORT trial: preoperative enoxaparin versus postoperative fondaparinux for thromboprophylaxis in bariatric surgical patients: a randomized double-blind pilot trial. Surgery for obesity and related diseases, 11(3), 672-683.\u003c/li\u003e\n \u003cli\u003eLin, H. Y., Lin, C. Y., Huang, Y. C., Hsieh, H. N., Yang, Y. W., Chang, L., \u0026amp; Shen, M. C. (2022). Deep vein thrombosis after major orthopedic surgery in Taiwan: A prospective cross-sectional study and literature review. Journal of the Formosan Medical Association, 121(8), 1541-1549.\u003c/li\u003e\n \u003cli\u003eNederpelt, C.J., Breen, K.A., El Hechi, M.W., Krijnen, P., et al. (2021). Direct oral anticoagulants are a potential alternative to low-molecular-weight heparin for thromboprophylaxis in trauma patients sustaining lower extremity fractures. Journal of Surgical Research. https://www.sciencedirect.com/science/article/pii/S0022480420307277\u003c/li\u003e\n \u003cli\u003eNelson, D.W., Simianu, V.V., Bastawrous, A.L., et al. (2015). Thromboembolic complications and prophylaxis patterns in colorectal surgery. JAMA Surgery. https://jamanetwork.com/journals/jamasurgery/article-abstract/2300999\u003c/li\u003e\n \u003cli\u003eNam, D., Nunley, R.M., Johnson, S.R., Keeney, J.A., et al. (2016). The effectiveness of a risk stratification protocol for thromboembolism prophylaxis after hip and knee arthroplasty. The Journal of Arthroplasty. https://www.sciencedirect.com/science/article/pii/S0883540315010840\u003c/li\u003e\n \u003cli\u003eShalhoub, J., Lawton, R., Hudson, J., Baker, C., Bradbury, A., Dhillon, K., ... \u0026amp; Davies, A. H. (2020). Graduated compression stockings as adjuvant to pharmaco-thromboprophylaxis in elective surgical patients (GAPS study): randomised controlled trial. bmj, 369.\u003c/li\u003e\n \u003cli\u003eKr\u0026ouml;ll, D., Nett, P. C., Rommers, N., Borb\u0026eacute;ly, Y., Deichsel, F., Nocito, A., ... \u0026amp; Stirnimann, G. (2023). Efficacy and safety of rivaroxaban for postoperative thromboprophylaxis in patients after bariatric surgery: a randomized clinical trial. JAMA network open, 6(5), e2315241-e2315241.\u003c/li\u003e\n \u003cli\u003eStannard, J. P., Lopez-Ben, R. R., Volgas, D. A., Anderson, E. R., Busbee, M., Karr, D. K., ... \u0026amp; Alonso, J. E. (2006). Prophylaxis against deep-vein thrombosis following trauma: a prospective, randomized comparison of mechanical and pharmacologic prophylaxis. JBJS, 88(2), 261-266.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Deep Vein Thrombosis, Heparin, Intermittent Pneumatic Compression, Pulmonary Embolism, Thromboprophylaxis","lastPublishedDoi":"10.21203/rs.3.rs-6501085/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6501085/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: We compared mechanical, pharmacological, and combined thromboprophylaxis strategies for preventing venous thromboembolism (VTE) in high-risk surgical patients using a Bayesian network meta-analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: To compare the efficacy and safety of mechanical, pharmacological, and combined thromboprophylaxis methods in preventing venous thromboembolism (VTE) among high-risk surgical patients through a systematic review and Bayesian network meta-analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: Ten randomized controlled trials (RCTs) and prospective cohort studies (n=12,286) were analyzed following PRISMA guidelines. Outcomes included incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, and mortality. Bayesian network meta-analysis assessed treatment effectiveness and safety.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Combined prophylaxis showed the highest likelihood of preventing DVT (SUCRA: 0.92) and PE (SUCRA: 0.89). Pharmacological prophylaxis had moderate efficacy but significantly increased major bleeding risk (OR: 1.37, 95% CrI: 1.01–1.84). Mechanical prophylaxis alone had the safest profile regarding bleeding but lower effectiveness in VTE prevention.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Combined prophylaxis optimizes VTE prevention but increases bleeding risks. Mechanical prophylaxis alone is safest for patients with high bleeding risk. Individualized, risk-based prophylaxis selection is recommended.\u003c/p\u003e","manuscriptTitle":"Mechanical vs. Pharmacological Thromboprophylaxis in High-Risk Surgical Cohorts: A Network Meta-Analysis of DVT Prevention and Bleeding Trade-offs","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-15 08:57:18","doi":"10.21203/rs.3.rs-6501085/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"edb65781-0640-4077-ae97-22db0dcd769f","owner":[],"postedDate":"October 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-15T08:57:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-15 08:57:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6501085","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6501085","identity":"rs-6501085","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}