Exploration of an Association Between UFH Dosing Based on Estimated Blood Volume and Venous Thromboembolism and Bleeding in the Underweight and Critically Ill

Abstract

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/m 2), critically ill patients. We performed a post hoc analysis of a retrospective cohort study that included adult intensive care unit patients who received standard-or 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

Evaluation of an Association Between Enoxaparin Dose per Estimated Blood Volume and Clinically Relevant Bleeding in Low-Weight Trauma Patients

“…The prevalence of clinically relevant VTE and bleeding in this study was consistent with similar analyses of low-weight and critically ill patients. 8,9,13,14 The prevalence of clinically relevant VTE was similar to that in contemporary analyses of trauma patients (0.5% vs 1.1%-1.9%), but the prevalence of clinically relevant bleeding was higher (6.9% vs 2.3%-4%). 4,7,21-23 This supports previous assertions that low-weight critically ill patients may be at risk of bleeding if prescribed what are considered “standard” or non–weight-adjusted VTE prophylaxis regimens.…”

“…In current literature, EBV has shown promise as a potential dose modifier for UFH in low-weight critically ill patients after suggesting a higher risk of clinically relevant bleeding with increased daily doses per milliliter of EBV in 2 separate analyses. 13,14 In addition, a recently published study in trauma patients with a mean BMI of 27.4 kg/m 2 found that enoxaparin dose (in mg) per liter of EBV was more closely correlated with recorded anti-Xa concentrations than enoxaparin dose per total body weight (TBW) or BMI. 7 Estimated blood volume has not been formally studied as a potential dose modifier in low-weight trauma patients to date.…”

Evaluation of anti‐factor Xa concentrations using a body mass index‐based enoxaparin dosing protocol for venous thromboembolism prophylaxis in trauma patients

“…However, in the current study, BMI‐based enoxaparin dosing resulted in only 62.6% of patients reaching target anti‐Xa concentrations, which is inadequate. Although not supported by outcome data, EBV‐based dosing represents a theoretically superior strategy because the body composition of a typical trauma patient (young, male, and muscular) results in a larger blood volume, but not necessarily higher BMI 16,17 . This study found that anti‐Xa concentrations correlated better with EBV than to BMI and TBW.…”

Multicenter study evaluating target attainment of anti‐Factor Xa levels using various enoxaparin prophylactic dosing practices in adult trauma patients

“…24 However, in a study of low-weight trauma patients weighing <60 kg, enoxaparin dose-per-unit EBV was not different between patients who did or did not bleed, and was not a significant predictor of bleeding in a logistic regression analysis. 39 With an increased sample size and broader population, our results also demonstrated that patients dosed using the EBV-based strategy had the highest percentage of anti-Xa levels at goal, but our study was not powered to detect any difference in bleeding or VTE. In pairwise comparison, the EBV dosing strategy was more than three times as likely to yield anti-Xa levels at or above target compared to BMI dosing strategy.…”

“…In one single‐center study with 241 trauma patients, patients dosed using an EBV‐based enoxaparin guideline were more likely to achieve target anti‐Xa levels 0.2–0.5 IU/mL compared to BMI‐based dosing (81% vs. 63%, aOR 2.02) 24 . However, in a study of low‐weight trauma patients weighing <60 kg, enoxaparin dose‐per‐unit EBV was not different between patients who did or did not bleed, and was not a significant predictor of bleeding in a logistic regression analysis 39 . With an increased sample size and broader population, our results also demonstrated that patients dosed using the EBV‐based strategy had the highest percentage of anti‐Xa levels at goal, but our study was not powered to detect any difference in bleeding or VTE.…”