The 2022 American Society for Metabolic and Bariatric Surgery (ASMBS) issued an updated position statement on perioperative venous thromboembolism (VTE) prophylaxis in bariatric surgery. The panel highlighted the ongoing lack of high-quality evidence concerning the safety, effectiveness, dosing, and duration of pharmacologic thromboprophylaxis during the peri-operative period. The complexity of dosage and timing further complicate the formulation of guidelines due to substantial variations. Pharmacoprophylaxis has not been extensively studied within the obese population, leading to uncertainties about the pharmacokinetics of these agents. Currently, there is no consensus or robust data regarding the optimal choice, dosing regimen, and duration of pharmacoprophylaxis after bariatric surgery. While conflicting data exist in the literature concerning the preferred type of pharmacoprophylaxis, various strategies involving single-agent and combined therapies of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) have been proposed. [1]
The most reliable data available to date suggest that LMWH provides more effective VTE prophylaxis in patients with severe obesity. This is attributed to its improved bioavailability and reduced risk of heparin-induced thrombocytopenia without significantly increasing bleeding risks. For patients with severe renal insufficiency (creatinine clearance [CrCl] <30 mL/min), the ASMBS recommended dose reduction of LMWH, dose adjustment based on anti-factor Xa (AFXa) levels, or even the use of UFH for VTE prophylaxis. Several dosing approaches have been suggested, including fixed dosing of LMWH (e.g., enoxaparin 40 mg BID), body mass index (BMI)-titrated dosing, and dose adjustment based on AFXa levels. Studies have indicated the safety of administering higher doses of subcutaneous enoxaparin (e.g., 60 mg vs. 40 mg) over a 12-hour period in the perioperative phase, particularly for patients with higher body mass index (BMI) (e.g., BMI ≥ 60 kg/m^2), without elevating the risk of significant bleeding. Moreover, extended courses of high-dose LMWH (10 to 14 days) for pharmacoprophylaxis have demonstrated safety in multiple investigations. Given the limited availability of high-quality literature guiding LMWH dosing, some higher-risk patients (e.g., extremely high BMI, known hypercoagulable states, or renal insufficiency) may benefit from post-discharge LMWH dosing adjustments based on AFXa levels. Although specific target prophylactic AFXa levels for LMWH lack robust support, peak concentrations of 0.2 to 0.4 IU/mL for VTE prophylaxis, measured four hours after the administration of the third LMWH dose, have been suggested. [1]
The Evidence-Based Clinical Practice Guidelines from the American College of Chest Physicians have indicated that patients undergoing bariatric procedures are at a heightened risk for VTE events. For individuals in this high-risk category who do not have a substantial risk of major bleeding complications, the recommendations advised considering pharmacologic prophylaxis using LMWH or low-dose UFH in conjunction with mechanical prophylaxis. Conversely, patients at elevated risk for significant bleeding complications, or those in whom the consequences of bleeding are deemed particularly severe, should prioritize mechanical prophylaxis until the bleeding risk subsides, at which point pharmacologic prophylaxis could be initiated. The guideline does not endorse a specific dose for obese bariatric surgery patients. [2]
The 2017 European guidelines on perioperative VTE prophylaxis proposed specific recommendations for obese patients undergoing bariatric procedures. For those with a low risk of VTE, the guidelines suggested using either anticoagulants or intermittent pneumatic compression (IPC). However, for obese patients with a high risk of VTE, which includes factors such as age over 55 years, BMI over 55 kg/m^2, history of VTE, venous disease, sleep apnea, hypercoagulability, or pulmonary hypertension, the panel recommended combining anticoagulants and IPC. Regarding the choice of anticoagulants, the guidelines preferred the use of LMWH over low-dose UFH. The suggested dose of LMWH for obese patients with a lower VTE risk is 3,000 to 4,000 anti-Xa IU every 12 hours subcutaneously, adjusted based on BMI. For obese patients with a higher VTE risk, a higher dose of LMWH, ranging from 4,000 to 6,000 anti-Xa IU every 12 hours subcutaneously, is recommended. Additionally, the guidelines advised extending the prophylaxis for patients at high VTE risk during the post-discharge period for a duration of 10 to 15 days. However, it's important to note that the lack of high-quality randomized trials with a low risk of bias limits the strength of the recommendations put forth by the panel. [3], [4]
A 2022 systemic review and meta-analysis (N= 15) summarized studies evaluating the use of VTE prophylactic regimens to determine optimal dosing, duration, and agents of use. Both LMWH and fondaparinux may be effective in reducing VTE risk without increasing major bleeding or mortality risk (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.14 to 7.39), but supporting evidence for this claim was rated low-quality. Pooled estimates suggest augmented LMWH dosing may both increase bleeding in comparison to standard dosing (OR 3.03, 95% CI 0.38 to 23.96) and show no added benefit in reducing VTE incidence (OR 0.57, 95% CI 0.07 to 4.39). Based on the incidence of post-surgery VTE events following discharge in observational studies, extended prophylaxis may show merit in patients who exhibit a higher VTE risk, but there is insufficient high-quality data to support this observation. There was no evidence regarding the efficacy of oral anticoagulants as peri-operative pharmacoprophylaxis in bariatric surgery. [5]
A review conducted in 2020 outlined an approach to preventing VTE after surgery. This review examined the assessment of postoperative VTE and bleeding risks in patients, as well as the delicate balance required to create an effective VTE prophylaxis plan. The appropriate dosing of heparin for obese patients remains uncertain. While therapeutic heparin dosage is typically determined based on a patient's total body weight, it is not as clear whether the standard prophylactic heparin doses offer adequate VTE protection for obese individuals. In bariatric surgery, research has suggested that higher doses of LMWH or low-dose UFH could slightly improve effectiveness in patients with significant obesity without a notable rise in bleeding risks. A summary of VTE prophylaxis recommendations following bariatric surgery can be found in Table 1. [6]
A 2022 literature review summarized evidence supporting the use of DOACs after bariatric surgery, utilizing 28 studies (7 cohort studies, 6 case series, and 15 case reports; N= 3,229 patients). Notably, no randomized trials were available. Included patients were treated with apixaban (n= 2,155 patients), an unspecified DOAC (n= 740), rivaroxaban (n= 319), dabigatran (n= 15), and edoxaban (n= 1). Two incidences of arterial thromboembolism were reported in 21 studies (N= 834 patients), corresponding to an incidence rate of 0.73 events per 100 person-years (95% confidence interval [CI] 0.01 to 5.10). Over 23 studies (n= 2,486 patients), 8 VTE events were reported, an incidence rate of 2.45 events per 100 person-years (95% CI 0.40 to 7.94). Incidences of major bleeds were reported 17 times in 23 studies (n= 3,217 patients), resulting in an incidence rate of 3.40 events per 100 person-years (95% CI 0.80 to 9.36). When assessing the impact of bariatric surgery on pharmacokinetics of individual DOACs, data from 8 studies (n= 42 patients) demonstrated that the pooled proportion of drug levels within the conventionally accepted peak therapeutic range was 58% (95% CI 39 to 74%) when comparing individual drug levels to expected steady-state concentrations documented in phase II and III clinical trials. Based on Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, the overall certainty of evidence was rated as very low for all outcomes due to risk of bias, indirectness, imprecision, and potential publication bias. Ultimately, the data collected within this review reveals a lack of high-quality evidence to guide the optimal use of DOACs after bariatric surgery. Similarly, other previous systematic reviews were also unsuccessful in their attempt to reach definitive conclusions regarding clinical benefit of DOACs after bariatric surgery. [7]
More specific to pharmacokinetic changes, a 2017 paper described the impact of gastrointestinal tract surgery on the absorption and efficacy of DOACs. As patients with significantly altered gastrointestinal tracts were not included in phase II and III DOAC efficacy and safety trials, available literature utilized in this review was limited to case series and case reports. Concerns related to DOACs in patients with major gastrointestinal tract surgery are primarily related to decreased absorption and subsequently decreased efficacy as opposed to increased toxicity. Bioavailability among different DOACs is highly variable, ranging from 7% (dabigatran) to > 80% (rivaroxaban), and can be further impacted by many factors in the gastrointestinal tract. The impact of different surgical interventions on bioavailability of each agent are summarized in Table 8. Based on the limited available evidence and isolated reports, rivaroxaban may be considered in patients who underwent major proximal or distal intestinal resections, but was recommended to be avoided in patients with total or partial gastrectomy. Dabigatran was associated with therapeutic failure in patients who underwent Roux-en-Y gastric bypass or had short bowel syndrome. Apixaban may be considered in patients undergoing Roux-en-Y gastric bypass due to its distal intestinal absorption and potentially gastrectomy, but not short bowel syndrome. Conversely, proximal absorption of edoxaban may translate to its potential use in short bowel syndrome. [8]
A 2022 survey investigated the variability between surgeon VTE prophylaxis practices within the United States. The survey of over 250 bariatric surgeons revealed a significant lack of standardization in VTE prophylaxis practices between providers. While nearly all surgeons utilized both mechanical and chemical prophylaxis during surgery, the specific types, dosages, timing, and duration varied widely. Doses differed in amount and frequency for chemical prophylaxis drugs like enoxaparin and heparin. Most administered chemoprophylaxis prior to the operation (80.9%) but the first post-operative dose varied (evening of surgery 44%; next morning 39.5%). Post-discharge extended prophylaxis ranged from 1 to 4 weeks without consensus. Additionally, the factors considered for determining extended prophylaxis eligibility varied between surgeons. The survey demonstrated differences across all domains of VTE prophylaxis, highlighting the need for larger prospective studies to define optimal protocols and improve standardization in this area, lacking clear evidence-based guidelines. [9]