The 2012 American College of Chest Physicians (ACCP) guidelines for the prevention of VTE in nonsurgical patients recommend for acutely ill hospitalized medical patients who are at increased risk of thrombosis to be on anticoagulant thromboprophylaxis with low-molecular-weight heparin (LMWH), low-dose unfractionated heparin (LDUH) twice daily, LDUH three times daily, or fondaparinux. The recommended prophylaxis dose for unfractionated heparin is 5000 units twice or three times daily; there is no distinct recommendation on doses for patients who are obese. [1], [2]
A 2016 review in response to the 2012 ACCP guidelines examined different chemical prophylaxis to prevent venous thromboembolism in morbidly obese patients (BMI > 40 kg/m2) since the specific patient population is not defined in previous ACCP guidelines. The paper concludes that if unfractionated heparin (UFH) is used, then the recommended dose is 7,500 units SQ TID (increased from 5,000 units BID to TID). The review advises using prophylactic doses of subcutaneous UFH in morbidly obese patients who also have renal impairment (CrCl <30 mL/min) instead of enoxaparin. [3]
A 2021 review evaluating drug dosing in critically ill obese patients discussed commonly used medications in the intensive care unit (ICU) for hemodynamic support or prophylaxis. Regarding VTE prophylaxis, studies assessing UFH dosing regimens for VTE prophylaxis in obese patients have mostly found no difference in VTE rates between standard and elevated doses. Therefore, 5,000 units UFH Q8H may be appropriate for VTE prophylaxis in critically ill obese patients; however, in more extreme obesity (BMI ≥ 50 kg/m2), 7,500 units of UFH Q8H may be considered. [4]
Due to the under-representation of obese patients in clinical trials, there are uncertainties regarding the optimal dosing for both safety and efficacy. Pharmacokinetic studies and small-scale cohort studies, which serve as the basis for current knowledge, suggest that weight-based dosing of UFH and LMWH is generally preferable over fixed dosing in obese patients for VTE treatment and prophylaxis. [5]
A 2021 systematic review and meta-analysis comprehensively evaluated the efficacy and safety of weight-adjusted versus fixed-dose heparin for VTE prevention in hospitalized obese patients. The analysis encompassed 12 studies, including prospective observational, retrospective, non-randomized, and randomized controlled trials, focusing on the occurrence of VTE, bleeding events, and anti-Xa levels. The review covered both LMWH and UFH regimens, with doses adjusted based on weight compared to standard fixed doses, such as the administration of enoxaparin 40 mg or heparin 5000 units. The studies involved a total of over 13,000 patients, detailing outcomes across various settings, including medical and surgical wards. The meta-analysis found no significant reduction in VTE occurrence with weight-adjusted heparin doses compared to fixed-dose regimens (odds ratio [OR] 1.03, 95% confidence interval [C.I.] 0.79 to 1.35). Additionally, bleeding risks were not significantly increased with weight-adjusted dosing (OR 0.84, 95% C.I. 0.65 to 1.08). However, weight-adjusted dosing was associated with higher anti-Xa levels (effect size [ES] 2.04, 95% C.I. 1.16 to 2.92, p<0.0001). Despite the higher anti-Xa levels, the study did not establish a direct clinical benefit in terms of VTE reduction or bleeding risk. The findings suggest that a fixed-dose heparin strategy might be sufficient for VTE prophylaxis in obese patients, without necessitating weight adjustments, which challenges existing practices of using weight-adjusted dosing in this population. [6]
A 2019 review found conflicting evidence (see Table 1) regarding the use of higher fixed doses of UFH for VTE prophylaxis in obese patients. Subjects were largely hospitalized patients without specifically identifying the critically ill population. The event rates for both VTE and bleeding complications varied widely across the included studies which further makes it difficult to formally conclude the outcomes of treatment with either treatment strategy. Overall, the authors concluded that there is insufficient data to recommend routine use of high-dose thromboprophylaxis in obese patients. [7]
Similarly conflicting results were found in a 2020 retrospective audit, however, which evaluated the dosing practices of UFH in obese patients at the Princess Alexandra Hospital in Queensland, Australia. The investigation analyzed 200 patients, divided into weight cohorts of <100 kg, 100–124.9 kg, 125–150 kg, and >150 kg, to determine if the current dosing practices led to inadequate anticoagulation. The primary outcome focused on the mean maintenance doses required to achieve two consecutive therapeutic activated partial thromboplastin times (APTTs) and the time to reach this endpoint. Results indicated that the mean maintenance doses in units per hour (U/h) increased consistently with weight, with doses of 1229±316, 1673±523, 2031±596, and 2146±846 U/h required for the respective weight cohorts. Interestingly, the weight-based doses in units per kilogram per hour (U/kg/h) showed a decreasing trend as weight increased, amounting to 16±4.1, 15.1±4.8, 14.9±4.2, and 11.6±4.2 for the cohorts, respectively. The 2020 audit revealed that the median time to achieve therapeutic APTTs was notably prolonged, with obese patients requiring 39 hours on average, suggesting that the dosing practices might be inadequate. A significant finding was the increased need for larger absolute doses of UFH (U/h) in obese patients, indicating that current nomograms based on total body weight might lead to underdosing when capped doses are applied. The investigation advises considering larger absolute doses but lower uncapped TBW-based doses as weight increases. The study underscores the need for revising UFH dosing strategies in obese populations to ensure timely and adequate anticoagulation, thereby advocating for larger doses that align with the pharmacokinetic and pharmacodynamic profiles observed in obese patients. Future research should focus on prospective trials to validate these findings and evaluate the clinical outcomes associated with modified dosing regimens. [8]