LAUSR

We undertook a post hoc analysis of study data published in the journal to further investigate the association between bleeding risk and the use of venous thromboembolism (VTE) prophylaxis in underweight, critically ill patients and to optimize its dosing.1 Given the low volume of distribution and 1-compartment model of unfractionated heparin (UFH), dosing based on estimated blood volume (EBV) could be used to improve safety and efficacy. Clinical utility has been suggested with this strategy in a previous study assessing therapeutic anticoagulation with UFH.2 We sought to describe the relationship between EBV, daily UFH dose, and the incidence of VTE and bleeding in underweight (≤50 kg or BMI ≤18.5 kg/m2), critically ill patients. We performed a post hoc analysis of a retrospective cohort study that included adult intensive care unit patients who received standardor reduced-dose VTE prophylaxis at a large academic medical center from September 2009 to March 2014. EBV was calculated using Nadler’s formula.3 Patients were stratified into lowdose UFH (<3.5 U/mL/d) and high-dose UFH (≥3.5 U/ mL/d) groups. This cutoff was derived from mean population kinetic data suggesting that a typical patient (EBV of 4.3 L) who receives UFH 5000 units subcutaneously every 8 hours would be exposed to ~3.5 U/mL/d.4 The primary end point assessed was the prevalence of clinically relevant bleeding and VTE in each group. A total of 255 patients were included in the analysis; 84 patients were included in the low-dose group, and 171 were included in the high-dose group. Baseline characteristics were similar between groups, with the exception of a higher proportion of female and surgical patients within the low-dose group. In all, 83% of patients received UFH 5000 units 3 times daily during the study period. Clinically relevant bleeding was more prevalent in the high-dose group (12.2% vs 8.3%, P = 0.343), whereas the prevalence of clinically relevant VTEs in both groups was comparable (5.8% vs 3.6%, P = 0.554). Exploration of higher-dose cutoffs of 4 and 4.5 U/mL/d yielded a trend of further increased bleeding rates in the high-dose groups (13.8% vs 8%, P = 0.136, and 14.1% vs 9.2%, P = 0.227, respectively), whereas VTE rates remained comparable (5.4% vs 4.8%, P = 0.832, and 6.5% vs 4.3%, P = 0.437, respectively; Table 1). Of note, the reported prevalence of bleeding in the highdose groups in each comparison exceeded those previously reported in this population.5 We, therefore, feel that UFH dosing based on EBV may be a useful predictor of clinically relevant bleeding in underweight, critically ill patients and may be a promising method by which to appropriately dose chemical VTE prophylaxis in these patients. However, these results must be interpreted in the context of their limitations, including study design, the unknown effect of confounding variables and missing data, and sample size. Therefore, more robust analyses utilizing this dosing strategy with larger sample sizes are needed to confirm the possible correlation postulated in this study. 909388 AOPXXX10.1177/1060028020909388Annals of PharmacotherapyCarter et al letter2020