Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology

Abstract

Background Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. Methods We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. Discussion This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. Systematic review registration PROSPERO CRD42021234119

Benefits and harms of direct oral anticoagulation and low molecular weight heparin for thromboprophylaxis in patients undergoing non-cardiac surgery: systematic review and network meta-analysis of randomised trials

“…In the supplementary material (table S13), we have provided examples of these calculations of baseline risks for symptomatic venous thromboembolism specific to the surgery or procedure; most were obtained from an ongoing systematic review of observational studies. 57 conclusions We showed that direct oral anticoagulants and LMWH probably reduce symptomatic venous thromboembolism in major non-cardiac surgery, and that direct oral anticoagulants probably have a relatively greater efficacy than LMWH at the standard prophylactic dose. All of the drug treatment options probably increase bleeding.…”

“…Decision makers can use our network relative treatment effects and combine them with trustful (and ideally up-to-date) baseline risk estimates specific to their population and surgery, to obtain absolute treatment effects for benefits and harms. In the supplementary material (table S13), we have provided examples of these calculations of baseline risks for symptomatic venous thromboembolism specific to the surgery or procedure; most were obtained from an ongoing systematic review of observational studies 57…”

Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper-Gastrointestinal and Hepatopancreatobiliary Surgery

“…Methods to evaluate the RoB in longitudinal cohort studies are less developed than the methods in randomized trials. 43 Through discussion and consensus building, and considering previous literature, [7][8][9][44][45][46] we developed an instrument to categorize RoB of the studies 12 that evaluated each study according to 6 domains: (1i) sampling of the study population, (2) reporting of thromboprophylaxis, (3) source of information, (4) whether a majority of patient recruitment years were earlier or later than 2010, (5) clear specification of duration of follow-up, and (6) study type (Supplemental Digital Content Appendix, page 146, Supplemental Digital Content 1, http://links.lww.com/SLA/E826). For each domain, we judged studies to have either a high or low RoB, classifying studies as follows: no high RoB domains as very low, 1 high RoB domain as low, 2 high RoB domains as moderate, and 3 or more high RoB domains as high overall RoB.…”

A Systematic Review of the Guidelines on Venous Thromboembolism Prophylaxis in Gynecologic Oncology

“…The main cause of death in middle-and high-income world regions is represented by cardiovascular diseases, as the World Health Organization (WHO) indicated. In developed countries, venous thromboembolic (VTEs) events ARE considered the third most common cardiovascular disease after coronary heart disease and stroke, with one case per The articles' research was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [20].…”