When patients have an elevated weight, do institutions cap the lower bolus of heparin when on a drip?

When patients have an elevated weight, do other institutions cap the lower bolus of heparin when on a drip? For example if the PRN bolus is 30-60 units/kg and a patient weighs 140 kg the bolus doses would be 8400 units and the capped upper dose would be 10,000 units. Do other institutions just cap both doses, thus 5,000 units and 10,000 units, or do they give 8400 units and 10,000 units?

Comment by InpharmD Researcher

While definitive data are lacking, available evidence supports weight-based heparin dosing rather than empiric capping, with close laboratory monitoring to ensure therapeutic anticoagulation. Clinical guidance for venous thromboembolism (VTE) recommends calculating bolus and infusion doses using total or adjusted body weight in obese and morbidly obese patients, noting that arbitrary caps may lead to under-anticoagulation. Studies show that adjusted body weight-based dosing achieves therapeutic anti-Xa levels in obese patients without increasing bleeding risk, and some evidence indicates that higher maximum doses can achieve therapeutic anticoagulation more rapidly without added bleeding in both obese and nonobese patients. Heparin dosing in obesity should be individualized, guided by patient-specific factors and careful laboratory monitoring rather than fixed dose limits.

Background

A 2016 expert clinical guidance on the practical management of heparin anticoagulants for venous thromboembolism (VTE) provides recommendations on dosing, monitoring, dose adjustment, and management in special populations, including those with extreme body weights. For obese and morbidly obese patients, the guidance recommends calculating heparin doses using either total or adjusted body weight, with close monitoring of early laboratory values to ensure timely achievement of therapeutic anticoagulation. The guidance also cautions that empiric dose caps may lead to under-anticoagulation and advises individualized dosing when caps are applied. Heparin infusion rates achieving therapeutic anticoagulation in this population have been reported to range from approximately 5 to 12.8 units/kg/hour. Notably, the guidance did not define a maximum heparin infusion rate in obese patients, emphasizing instead the importance of ensuring the therapeutic threshold is reached promptly. Due to limited data, institutions are encouraged to use weight-based nomograms and conduct internal audits (e.g., assess the responsiveness of the health system’s aPTT reagent and coagulation instrument) to guide dosing according to their own monitoring systems and patient populations. Overall, heparin dosing in obesity, including infusion rate adjustments, should be guided by patient-specific factors, institutional experience, and careful monitoring to balance effective anticoagulation with the risk of bleeding. [1]

The 2012 American College of Chest Physicians (ACCP) guidelines for antithrombotic therapy and prevention of thrombosis recommend administering 70 units/kg bolus of intravenous (IV) unfractionated heparin (UFH) followed by 15 units/kg/h infusion in cardiac or stroke patients. The infusion dose should be adjusted based on laboratory values and institution-specific nomograms. The ACCP does not specify whether to use total body weight (TBW), ideal body weight (IBW), or adjusted body weight (ABW) to calculate the dose. [2]

Per the American College of Cardiology (ACC), patients with ST-elevation myocardial infarction (STEMI) should receive a bolus dose of UFH (50-70 units/kg) with GP IIb/IIIa receptor antagonists or 70-100 units/kg bolus without GP IIb/IIIa receptor antagonists. With fibrinolysis, UFH 60 units/kg (maximum 4,000 units), followed by 12 units/kg/h (maximum 1,000 units) adjusted by laboratory values is recommended for 48 hours or until revascularization. In non-STEMI patients, the ACC recommends 60 units/kg (maximum 4,000 units) followed by 12 units/kg/h (maximum 1,000 units/h) adjusted by aPTT for 48 hours or until percutaneous coronary intervention (PCI) is performed. For patients > 100 kg, it suggests using the fixed-dose regimen (5,000 units bolus followed by 1,000 units/h). During PCI, if the patient did not receive prior anticoagulation and GP IIb/IIIa inhibitor therapy is planned, heparin 50-70 units/kg is recommended to achieve activated clotting time (ACT) of 200-250 seconds. If GP IIb/IIIa inhibitor therapy is not planned, 70-100 units/kg is recommended to achieve an ACT of 250-300 seconds (HemoTec) or 300-350 seconds (Hemochron). If the patient was previously anticoagulated, it states to give additional doses to achieve the same ACT requirements based on GP IIb/IIIa use. It is not specified if weight-based dosing calculations are based on TBW, IBW, or ABW. [3], [4]

The ACCP guidelines recommend an initial unfractionated heparin bolus dose of 80 units/kg for the treatment of venous thromboembolism (VTE), without specific discussion of dose capping. The 2012 ACCP guidelines for the prevention of VTE in nonsurgical patients do not provide separate dosing recommendations for individuals with obesity. [5], [6]

A 2016 review examined different chemical prophylaxis to prevent VTE in morbidly obese patients (BMI > 40 kg/m2) since the specific patient population is not defined in the guidelines. If UFH is used, then the dose is 7,500 units subQ 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. The author cited one large retrospective study that shows UFH 5,000 units twice to thrice daily, up to 7500 units three times daily, to have a lower rate of VTE than standard dosing. [7]

A 2018 review questioned the dosing of VTE prophylaxis as obesity rates are rising. It was highlighted that obesity is an independent risk factor for VTE in both men and women, and as of 2008, around 5.7% of the US population has a BMI >40 kg/m2. Pharmacological dosing of UFH is well established for normal-weight patients, but dosing in obese patients might vary due to an increased volume of distribution of lipophilic drugs. Literature suggests that larger than standard doses of UFH may be warranted to provide optimal VTE prophylaxis in morbidly obese patients. The problem is that these patients are underrepresented in clinical studies, so there is no way to make a confident recommendation of the dose needed. All studies included in this review also excluded patients with renal impairment. The authors postulate that subQ UFH thrice daily of doses at least 5,000 units may be adequate in morbidly obese patients for VTE prophylaxis. Even though higher doses may be indicated, the available evidence does not allow for more specific dosing recommendations. However, the authors state that these doses may not be appropriate for patients with renal impairment due to a lack of evidence. [8]

A 2009 review explored the necessity of capping low-molecular-weight heparin (LMWH) doses for obese patients in Canada. The review involved a comprehensive analysis of English-language publications and literature on LMWH used at treatment doses in obese individuals. Five pharmacokinetic or pharmacodynamic studies were examined, showing no evidence of excess accumulation of LMWHs in obese patients. Additionally, 11 trials related to LMWH use in patients with acute coronary syndromes and VTE were identified, though only 7 provided sufficient information. Subgroup analysis from several trials indicated no increased bleeding risk for obese patients treated with enoxaparin without dose capping. Notably, studies showed that dalteparin did not lead to excessive accumulation when dose caps were removed, supported by anti-Xa level assessments. In conclusion, the literature reviewed in the article suggests that dose capping of LMWHs for obese patients is largely unjustified. Although data is scarce for individuals over 150 kg, findings indicate that therapeutic doses should be calculated based on body weight up to this limit. Despite the limited scope of available studies and the absence of substantial quality data, the evidence advocates for weight-based dosing without caps to ensure efficacy and safety in treatment. [9]

Literature Review

A search of the published medical literature revealed 10 studies investigating the researchable question:

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-10 for your response.

Summary of Studies Using Weight-Based Dosing Therapeutic Unfractionated Heparin
Citation	Design/population	Intervention	Results
Shlensky et al.; 2020¹	Retrospective chart review N= 423 Non-obese (n= 230) Obese (n= 146) Morbidly obese (n= 47)	Upon initiation, patients received an optional 80 units/kg bolus of unfractionated heparin (UFH) followed by a continuous infusion starting at 18 units/kg/hour. Doses were calculated using actual body weight (ABW) regardless of body size. The first activated partial thromboplastin time (aPTT) was to be checked 6 hours following the infusion start per protocol.	There were no significant differences in achieving therapeutic aPTT between the groups (obese vs non-obese (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.82–1.26, p= 0.88; morbidly obese vs non-obese: HR 0.87, 95% CI: 0.62–1.21, p= 0.41). The cumulative incidence for achievement of subtherapeutic aPTT was statistically significant between the morbidly obese and non-obese groups (HR 0.78, 95% CI: 0.60–1.02, p < 0.001) but not between the obese and the non-obese groups (HR 0.39, 95% CI: 0.24–0.64, p= 0.065). There was no significant difference in major bleeding events among the body-mass index (BMI) groups (obese vs non-obese, p= 0.91; morbidly obese vs non-obese, p= 0.98).
George et al.; 2020²	Retrospective chart review N= 200 < 100 kg (n= 34) 100–124.9 kg (n = 122) 125–150 kg (n= 27) > 150 kg (n= 17)	Obesity was described as a weight > 100 kg. Actual body weight was used for dosing UFH.	Dose requirements in U/h exhibited a proportional relationship to TBW, however, the trend became inversely related for U/kg/h. UFH dose capping led to a significantly greater number of obese patients requiring infusion doses above the initial recommendation in order to attain a therapeutic aPTT compared to the < 100 kg cohort (p = 0.0047). The proportion of patients achieving a first therapeutic aPTT was not significantly different with 52.9% in non-obese and 54.2% in obese patients (p= 0.89).
Fan et al.; 2016³	Single-center, retrospective cohort study N= 168 Obese (n= 77) Nonobese (n= 148)	Data were collected after implementing a revised high-intensity heparin protocol specifying adjusted body weight-based dosing for obese patients.	Although no statistical between-group difference was seen in the percentages of first aPTT values in the target range, a significantly lower proportion of obese patients had above-target values (44.2% versus 59.5% of non-obese patients, p= 0.04). Obese patients were significantly more likely to have a below-target aPTT value (39% versus 19.6%, p= 0.003). The infusion rate required to achieve a first aPTT in the target range in the obese cohort was 18.2 units/kg/hr, as compared with a mean rate of 16.5 units/kg/hr in the nonobese cohort (p= 0.008). There was no difference between the two cohorts with regard to the rate of clinically significant bleeding or rates of major and nonmajor bleeding events.
Gerlach et al.; 2013⁴	Retrospective chart review N= 62 Non-obese (n= 21) Obese (n= 21) Morbidly obese (n= 20)	Patients received UFH (without a bolus) based on actual body weight at an initial infusion rate of 16 units/kg/h if non-obese or 12 units/kg/h if obese or morbidly obese.	At the time of the first therapeutic aPTT, the mean total doses of UFH were significantly higher in obese patients (878 ± 341 units/h non-obese, 1,051 ± 347 units/h obese, vs. 2,007 ± 648 units/h morbidly obese, p< 0.001), suggesting an influence of weight. When dosing was corrected for weight using ideal body weight (IBW), there were similar statistically significant differences in these dosages (14.3 ± 4.8 units/kg/h non-obese, 18.0 ± 5.9 units/kg/h obese, vs. 30.1 ± 8.4 units/kg/h morbidly obese, p< 0.001). In contrast, when dosed using actual body weight, there were no significant differences (13.5 ± 4.0 units/kg/h non-obese, 11.7 ± 4.5 units/kg/h obese, vs. 12.5 ± 2.9 units/kg/h morbidly obese, p= 0.35). Unlike dosing at first therapeutic aPTT, correction of doses using actual body weight did not resolve the discrepancy in doses for achieving a steady state (16.3 ± 5.3 units/kg/h non-obese, 11.6 ± 5.5 units/kg/h obese, vs. 11.1 ± 1.2 units/kg/h morbidly obese, p= 0.01).
Smith et al.; 2010⁵	Retrospective cohort, single-center N= 50 Non-obese (n= 33) Obese (n= 17)	Obesity was described as a weight > 100 kg. All patients received a bolus dose of UFH 26 units/kg, followed by an intravenous infusion of 15 units/kg/hr based on actual body weight, with no maximum dosage. Anti-factor Xa levels were measured according to the institution's protocol. The target range of anti-factor Xa was defined as 0.3-0.7 unit/mL.	The anti-factor Xa concentration was within the target range 6 hours after infusion initiation for 26 patients (52%; 0.65 ± 0.35 unit/ mL). The anti-factor Xa concentration was within the target range 24 hours after infusion initiation for 46 patients (92%). Of 17 obese patients, 16 (94%) reached a value within the target range within 24 hours. Out of 33 non-obese patient, 29 (88%) achieved values within the target range within 24 hours (p > 0.05).
Barletta et al.; 2008⁶	Retrospective chart review N= 101 Morbidly obese (n= 38) Non-morbidly obese (n= 63)	Morbidly obese was identified as having a BMI of ≥ 40 kg/m². All heparin doses were calculated based on actual body weight. Dosing consisted of an 80 units/kg bolus followed by an 18 units/kg/hr infusion rate. No dose cap or maximal bolus was used. The institution-specific therapeutic range for activated partial thromboplastin time aPTT value was 70–110 seconds.	Greater aPTT values were observed at both 6 hours (155 ± 37 versus 135 ± 44, p= 0.020) and 12 hours (141 ± 45 versus 117 ± 45, p= 0.012) for patients with morbid obesity than for non-morbidly obese patients. The number of heparin dosing adjustments was greater in the morbidly obese patients for the first 24 hours (71% for morbidly obese patients vs 50% for non-morbidly obese patients (p= 0.041) According to multivariate analysis, increasing BMI (odds ratio 1.06, 95% confidence interval 1.02–1.1; p= 0.003) was a significant predictor of supratherapeutic aPTT values. Four patients (4%) with BMI of 26.9, 38.6, 38.6, and 39 kg/m² experienced bleeding events. Only 2 of these patients had a supratherapeutic aPTT value.
Riney et al; 2010⁷	Single-center, prospective, observational cohort study N= 273 BMI >40 (n= 94) BMI 25–39.9 (n= 92) BMI < 25 (n= 87)	Class III obesity was defined as having a BMI of ≥40 kg/m². UFH infusions calculated an optimal bolus dose and initial infusion rate based on the patient’s actual body weight and indication.	The mean infusion rate required to obtain a first therapeutic aPTT was 11.5 units/kg/h in the class III obesity group versus 12.5 units/kg/h and 13.5 units/kg/h for the overweight/class I–II obesity and normal/underweight groups, respectively (p= 0.001). The mean times to a first therapeutic aPTT were 21.3, 22.1, and 29.9 hours, respectively (p = 0.421). There was a statistically significant difference in the infusion rate required to obtain 2 consecutive therapeutic aPTTs between groups 11.5 units/kg/h versus 12.7 units/kg/h in the overweight/class I–II obesity group and 13 units/kg/h in the normal/underweight group (p = 0.016). However there was no significant difference in the time to reach 2 consecutive therapeutic aPTTs. There was no significant difference in bleeding (p = 0.517) or mortality (p = 0.475) among groups.
Hurewitz et al.; 2011⁸	Retrospective observational chart review N= 84	Adult inpatients with VTE and a body mass index ≥30 kg/m2 treated with UFH. The analysis compared the recommended dose (80 units/kg of actual body weight) to the actual prescribed doses.	Time to attainment of therapeutic anticoagulation exceeded 24 hours in 29% of study patients and exceeded 48 h in 14% of patients. In 89%, the prescribed bolus dose fell below the recommended dose of 80 units/kg, and in 76% the initial continuous infusion fell more than 100 units/h below the recommended dose of 18 units/kg/h. There was a significant correlation between time to therapeutic anticoagulation and initial infusion dose (Spearman r=–0.27; p<0.02). Each decrease of 1 unit/kg/h translated to a delay ranging from about 0.75 h to 1.5 h over the range of prescribed doses (6 to 22 units/kg/h).
Floroff et al.; 2017⁹	Retrospective cohort study N= 197 Standard dosing (n= 71) Aggressive dosing (n= 126)	Adult patients with NSTEMI/UA or atrial fibrillation, or other cardiac indications treated with at least 6 hours of continuous UFH infusion. Patients were divided into standard dosing or aggressive dosing with a higher max dose and infusion rate. UFH dosing was calculated based on patient's actual body weight which consisted of UFH 60 units/kg bolus followed by 12 units/kg/hour.	A significantly higher proportion of patients treated with the aggressive strategy achieved a therapeutic aPTT within 6 hours (23% vs 11%, p=0.043). The delay or failure to achieve therapeutic anticoagulation was particularly evident in obese patients in the standard dosing group. The mean ± SD initial infusion rate was 10.8 ± 1.4 units/kg/hour in the standard dosing group versus 12 ± 0.02 units/kg/hour in the aggressive strategy group (p=<0.0005). The occurrence of supratherapeutic aPTT values and the highest aPTT achieved were similar between the two dosing groups (p=0.817 and p=0.348, respectively). No bleeding events were reported in either group.
Hosch et al.; 2017¹⁰	Retrospective cohort study N= 298 Nonobese (n= 121) Obese (n= 110) Severely obese (n= 63)	Adult patients with VTE and received heparin treatment, separated into three weight groups: nonobese (< 30 kg/m²), obese (BMI = 30 to 39.9 kg/m²), and severely obese (BMI ≥ 40 kg/m²). UFH was dosed based on patient's actual body weight unless the patient is over 20% of their ideal body weight, at which point a dosing body weight is used. Dosing body weight is calculated as: IBW + [0.4 (ABW - IBW)].	Median times to therapeutic aPTT (hours:minutes) in the nonobese, obese, and severely obese were 15:00 (interquartile range [IQR] = 8:05-23:21), 15:40 (IQR = 9:22-25:10), and 15:22 (IQR = 7.54- 23:40), respectively (P = 0.506). There was no difference in bleeding among the nonobese (14%), obese (13.9%), or severely obese groups (7.9%; p= 0.453). No adverse thrombotic events occurred during hospitalization.
Shin et al.; 2015¹¹	Retrospective chart review N= 240 <100 kg (n= 60) 100 to < 125 kg (n= 60) 125 to < 150 kg (n= 60) ≥ 150 kg (n= 59)	Obese adult patients who received continuous UFH divided into four weight categories: <100, 100 to < 125, 125 to < 150 and ≥ 150 kg. UFH dosing at first therapeutic aPTT was calculated using the patient's actual body weight.	The mean first therapeutic heparin dose was approximately 16.0 units/kg per hour in the less than 100 kg group and 11.3–13.0 units/kg per hour in larger weight groups. The incidence rates of hemorrhagic complications appeared similar across the groups. Actual body weight is the best predictor of a patient’s requirement of heparin, but heparin infusion rates should be reduced in obese patients.
Hohner et al.; 2015¹²	Retrospective cohort study N= 547 Control (n= 74) High weight (n= 76) Higher weight (n= 56)	Obese adults in the intensive care units treated with continuous UFH are divided into three weight groups: 95 to 104 kg (control), 105 to 129 kg (high weight), and greater than or equal to 130 kg (higher weight). UFH dosing was calculated using the patient's actual body weight.	To achieve therapeutic activated partial thromboplastin times, higher weight patients had higher mean infusion rates compared with control (2017 vs 1582 U/h; P= .002). Mean weight-based therapeutic infusion rate was lower in the higher weight group compared with control (13.1 vs 15.8 U/kg/h; p= .008). Post hoc analyses indicated mean weight-based infusion rate to achieve therapeutic anticoagulation was 15 U/kg/h in patients less than 165 kg and 13 U/kg/h in patients greater than 165 kg.
Kuhn et al.; 2021¹³	Retrospective cohort study N= 56 Obese (n= 22) Nonobese (n= 34)	Obese pediatric patients age < 21 years who received UFH infusion at a target anti-FXa goal of 0.35 to 0.7 units/mL. Patients received uncapped, actual body weight-based dosing of UFH.	Obese patients achieved therapeutic anti-FXa significantly faster than nonobese patients (median 4 vs 12 hours, p= .0192) and were more likely to have any supra-therapeutic anti-FXa levels (77% vs 35%; p= .0021). There was no statistically significant difference in major or clinically relevant nonmajor bleeding rates between weight categories (p= .69).
Hong et al.; 2016¹⁴	Observational, prospective study N= 78 Quartile 1 (n= 20) Quartile 2 (n= 20) Quartile 3 (n= 18) Quartile 4 (n= 20)	Male, adult patients undergoing percutaneous coronary intervention receiving weight-based UFH are divided into four weight categories according to their body mass index. UFH dosing was calculated using the patient's actual body weight.	Significant differences were found in overall maximum post‐UFH ACT values among all BMI quartiles. UFH doses per blood volume were significantly different among the BMI quartiles, showing a positive association with BMI quartiles; further evidence revealed that the areas under the ΔACT‐time curves increased gradually from quartile I to quartile IV. The proportions of ACT60 > 250s and ACT60 > 300s were found to be positively correlated with the increased BMI at 60 min after heparin loading.
Isherwood et al.; 2017¹⁵	Retrospective study N= 296 Nonobese (n= 148) Obese (n= 148)	Adult obese patients matched to non-obese patients who were treated with UFH for greater than 24 hours and standardized with anti-Xa. Obese was defined as having BMI ≥ 30 kg/m² Patients were further divided based on the UFH dosing protocol they received: high (target antifactor Xa 0.3–0.7 IU/mL), moderate (0.3–0.5 IU/mL), or low (0.1–0.2 IU/mL) UFH dosing was calculated using the patient's actual body weight.	Obese patients required a significantly lower mean weight-based infusion rate to attain first therapeutic antifactor Xa level compared to non-obese patients in both the high dose (19.45 vs. 15.29 units/kg/h, p<0.001) and the moderate dose populations (15.0 vs. 12.94 units/kg/h, p=0.003). Patients in both the high and moderate dose populations had significant differences in mean infusion rates to attain second consecutive therapeutic antifactor Xa levels. There was no difference between major bleeding or mortality outcomes.
Yee et al.; 1998¹⁶	Retrospective, observational study N= 213 Obese (n= 123) Nonobese (n= 90)	Patients who received weight-based heparin based on actual body weight, ideal body weight, or dosing weight. Patients were divided into obese (10kg or greater in excess of their IBW) or nonobese (10 kg less than excess of their IBW) groups.	Although the ranges were similar for all weight bases, ABW produced the tightest grouping of infusion rates between the 20th and 80th percentiles. The differences between infusion rates determined on the basis of DW, IBW, and ABW were significant (p < 0.001). there was a marked difference between the initial infusion rate (18 units/kg/hr) used in the current protocol and the actual rate at which a therapeutic PTT was achieved (p < 0.001 for DW versus IBW, DW versus ABW, and IBW versus ABW). In obese patients, there were significant differences between infusion rates calculated using DW, IBW, or ABW. In nonobese patients, no significant differences were observed.

References:
[1] [1] Shlensky JA, Thurber KM, O'Meara JG, et al. Unfractionated heparin infusion for treatment of venous thromboembolism based on actual body weight without dose capping. Vasc Med. 2020;25(1):47-54. doi:10.1177/1358863X19875813
[2] [2] George C, Barras M, Coombes J, Winckel K. Unfractionated heparin dosing in obese patients. Int J Clin Pharm. 2020;42(2):462-473. doi:10.1007/s11096-020-01004-5
[3] [3] Fan J, John B, Tesdal E. Evaluation of heparin dosing based on adjusted body weight in obese patients. Am J Health Syst Pharm. 2016;73(19):1512-1522. doi:10.2146/ajhp150388
[4] [4] Gerlach AT, Folino J, Morris BN, Murphy CV, Stawicki SP, Cook CH. Comparison of heparin dosing based on actual body weight in non-obese, obese and morbidly obese critically ill patients. Int J Crit Illn Inj Sci. 2013 Jul;3(3):195-9. doi: 10.4103/2229-5151.119200
[5] [5] Smith ML, Wheeler KE. Weight-based heparin protocol using antifactor Xa monitoring. Am J Health Syst Pharm. 2010;67(5):371-374. doi:10.2146/ajhp090123
[6] [6] Barletta JF, DeYoung JL, McAllen K, Baker R, Pendleton K. Limitations of a standardized weight-based nomogram for heparin dosing in patients with morbid obesity. Surg Obes Relat Dis. 2008;4(6):748-753. doi:10.1016/j.soard.2008.03.005
[7] [7] Riney JN, Hollands JM, Smith JR, Deal EN. Identifying optimal initial infusion rates for unfractionated heparin in morbidly obese patients. Ann Pharmacother. 2010;44(7-8):1141-1151. doi:10.1345/aph.1P088
[8] [8] Hurewitz AN, Khan SU, Groth ML, Patrick PA, Brand DA. Dosing of unfractionated heparin in obese patients with venous thromboembolism. J Gen Intern Med. 2011;26(5):487-491. doi:10.1007/s11606-010-1551-2
[9] [9] Floroff CK, Palm NM, Steinberg DH, Powers ER, Wiggins BS. Higher Maximum Doses and Infusion Rates Compared with Standard Unfractionated Heparin Therapy Are Associated with Adequate Anticoagulation without Increased Bleeding in Both Obese and Nonobese Patients with Cardiovascular Indications. Pharmacotherapy. 2017;37(4):393-400. doi:10.1002/phar.1904
[10] [10] Hosch LM, Breedlove EY, Scono LE, Knoderer CA. Evaluation of an Unfractionated Heparin Pharmacy Dosing Protocol for the Treatment of Venous Thromboembolism in Nonobese, Obese, and Severely Obese Patients. Ann Pharmacother. 2017;51(9):768-773. doi:10.1177/1060028017709819
[11] [11] Shin S, Harthan EF. Safety and efficacy of the use of institutional unfractionated heparin protocols for therapeutic anticoagulation in obese patients: a retrospective chart review. Blood Coagul Fibrinolysis. 2015;26(6):655-660. doi:10.1097/MBC.0000000000000336
[12] [12] Hohner EM, Kruer RM, Gilmore VT, Streiff M, Gibbs H. Unfractionated heparin dosing for therapeutic anticoagulation in critically ill obese adults. J Crit Care. 2015;30(2):395-399. doi:10.1016/j.jcrc.2014.11.020
[13] [13] Kuhn AK, Saini S, Stanek J, Dunn A, Kumar R. Unfractionated heparin using actual body weight without dose capping in obese pediatric patients-Subgroup analysis from an observational cohort study. Pediatr Blood Cancer. 2021;68(3):e28872. doi:10.1002/pbc.28872
[14] [14] Hong X, Shan PR, Huang WJ, et al. Influence of Body Mass Index on the Activated Clotting Time Under Weight-Based Heparin Dose. J Clin Lab Anal. 2016;30(2):108-113. doi:10.1002/jcla.21823
[15] [15] Isherwood M, Murphy ML, Bingham AL, Siemianowski LA, Hunter K, Hollands JM. Evaluation of safety and effectiveness of standardized antifactor Xa-based unfractionated heparin protocols in obese versus non-obese patients. J Thromb Thrombolysis. 2017;43(4):476-483. doi:10.1007/s11239-016-1466-9
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Use of Higher Maximum Doses and Infusion Rates Compared with Those Used in Standard Unfractionated Heparin Therapy Is Associated with Adequate Anticoagulation without Increased Bleeding in Both Obese and Nonobese Patients with Cardiovascular Indications
Design	Retrospective cohort study N= 197
Objective	To evaluate the time to achieve therapeutic activated partial thromboplastin time (aPTT) values and occurrence of bleeding based on standard unfractionated heparin (UFH) weight-based dosing recommendations compared with an aggressive weight-based UFH dosing strategy using higher maximum doses and infusion rates in both obese and nonobese patients who presented with non–ST-Segment Elevation Myocardial Infarction or unstable angina (NSTEMI/UA) or atrial fibrillation
Study Groups	Standard UFH dosing (n= 71) Aggressive UFH dosing (n= 126)
Inclusion Criteria	Patients aged 18 years or older who received at least 6 hours of a continuous UFH infusion for the management of unstable NSTEMI/UA or AF, or other cardiac indications
Exclusion Criteria	Patients who experienced deviations from either dosing strategy, including changes to aPTT goals and altered initial infusion rates, or if the UFH infusion was interrupted before at least one aPTT was measured during the infusion
Methods	Patients received either standard UFH dosing (60-unit/kg bolus [max 4000 units] followed by 12 units/kg/hour [max 1000 units/hour]) or aggressive UFH dosing (60-unit/kg bolus [max 10,000 units] followed by 12 units/kg/hour [max 2250 units/hour]). Both protocols included laboratory monitoring and guidance for nurses to titrate the infusion based on coagulation parameters.
Duration	September 2013 to February 2014 (standard dosing) October 2014 to March 2015 (aggressive dosing)
Outcome Measures	Primary: Achievement of therapeutic aPTT value within 6 hours Secondary: Time to achieve therapeutic aPTT, initial UFH infusion rate, incidence of supratherapeutic aPTT values, highest aPTT value, additional UFH bolus doses required for subtherapeutic aPTT
Baseline Characteristics		Standard Dosing Group (n=71)	Aggressive Strategy Group (n=126)	p-value
	Age (yrs)	62.4 ± 13.3	63.2 ± 12	0.691
	Weight (kg)	86.5 ± 21.2	88.5 ± 24.2	0.546
	Body mass index (kg/m2)	29.23 ± 6.44	29 ± 8	0.149
	Baseline aPTT (sec)	31.1 ± 5.9	31.8 ± 6.1	0.489
	Initial UFH infusion rate (units/kg/hr)	10.8 ± 1.4	12 ± 0.02	<0.0005
	Initial UFH bolus dose (units/kg)	53 ± 10	59.6 ± 7.6	<0.0005
Results		Standard Dosing Group (n=71)	Aggressive Strategy Group (n=126)	p-value
	aPTT therapeutic within 6 hours	8 (11)	29 (23)	0.043
	Time to therapeutic aPTT (hrs), median (95% CI)	21 (14.7–27.3)	15 (13.1–16.9)	0.036
	Required UFH bolus dose due to subtherapeutic aPTT (<40 msec)	26 (37)	32 (25)	0.097
	Patients with any supratherapeutic aPTT	33 (47)	76 (60)	0.817
Adverse Events	No bleeding events were reported in either group
Study Author Conclusions	Patients who had higher UFH maximum bolus doses and infusion rates achieved therapeutic anticoagulation more rapidly, without increased bleeding, and these doses can be adjusted for obese as well as nonobese patients. However, despite use of the higher doses, only 23% of patients achieved therapeutic aPTT values within 6 hours, suggesting that an even higher bolus dose and infusion rate may still be warranted.
Critique	This study was limited by its retrospective design, single-center setting, and relatively small sample size, which may affect the generalizability of the findings. The potential for incomplete documentation in a retrospective chart review may have led to underreporting of adverse events. Additionally, no patients in the aggressive strategy group met the higher dose cap, so it is unclear if the maximum dose in the updated dosing recommendations is appropriate based on these results. Further studies with larger sample sizes are needed to determine optimal UFH dosing regimens for obese patients.

References:
[1] Floroff CK, Palm NM, Steinberg DH, Powers ER, Wiggins BS. Higher Maximum Doses and Infusion Rates Compared with Standard Unfractionated Heparin Therapy Are Associated with Adequate Anticoagulation without Increased Bleeding in Both Obese and Nonobese Patients with Cardiovascular Indications. Pharmacotherapy. 2017;37(4):393-400. doi:10.1002/phar.1904

Continuous Intravenous Heparin Infusion Prevents Peri-operative Thromboembolic Events in Bariatric Surgery Patients
Design	Retrospective cohort study N= 822
Objective	To evaluate the efficacy and safety of continuous low-dose intravenous heparin infusion in preventing perioperative thromboembolic events in bariatric surgery patients
Study Groups	All patients (n= 822)
Inclusion Criteria	All bariatric operations from January 2000 until July 2005, including laparoscopic gastric bypass, Lap-Band®, and revisional operations
Exclusion Criteria	Not specified
Methods	Continuous intravenous unfractionated heparin administered at 400 U/hr (9,600 U/day) starting 1 hour before surgery, maintained until discharge. No bolus was given, and dosage was not adjusted for weight, PTT, or anti-Xa levels. Heparin was discontinued on discharge or earlier if bleeding risk was identified.
Duration	November 2000 to July 2005
Outcome Measures	Primary: Incidence of thromboembolic events Secondary: Incidence of bleeding requiring transfusion, anti-Xa levels, prothrombin time
Baseline Characteristics		All patients (n= 822)
	Mean age, years (range)	43±11 (15-74)
	Mean BMI (range)	45.2±7.1 (30-86)
	Mean ASA classification	3
Results		All patients (n= 822)
	Clinically evident thromboembolic event	1 (0.12%)
	Bleeding requiring transfusion	1.3%
	Heparin therapy terminated or held	5%
	Average estimated blood loss during surgery, cc	36 (5-500)
	Normal anti-Xa levels and prothrombin time	40 patients
Adverse Events	Bleeding requiring transfusion in 1.3% of patients. One patient received excessive heparin due to pump error without significant sequelae.
Study Author Conclusions	Continuous low-dose intravenous heparin therapy is associated with an extremely low incidence of thromboembolic events and a low risk for perioperative hemorrhage. It is inexpensive and rapidly reversible.
Critique	The study demonstrates a low incidence of thromboembolic events with continuous intravenous heparin, but lacks a control group for direct comparison. The retrospective design and lack of randomization may introduce bias. The study's findings are limited by the absence of routine surveillance for thromboembolic events and reliance on clinical diagnosis alone. The cost-effectiveness and rapid reversibility of the protocol are strengths, but the generalizability of the results may be limited by the single-center setting and specific patient population.

References:
[1] Quebbemann, B., Akhondzadeh, M. & Dallal, R. Continuous Intravenous Heparin Infusion Prevents Peri-operative Thromboembolic Events in Bariatric Surgery Patients. OBES SURG 15, 1221–1224 (2005). https://doi.org/10.1381/096089205774512528

Dosing of Unfractionated Heparin in Obese Patients with Venous Thromboembolism
Design	Three-year, cross-sectional consecutive case series N= 84
Objective	To examine the use of unfractionated heparin in obese patients with VTE at an academic teaching hospital in order to document the extent and pattern of underprescribing in this high-risk patient population
Study Groups	All patients (n= 84)
Inclusion Criteria	Adult inpatients with VTE and a body mass index ≥30 kg/m2 who were treated with unfractionated heparin
Exclusion Criteria	Not specified
Methods	Patients were identified from radiology and nuclear medicine logs. Data included patient demographics, heparin dosing, and time to therapeutic anticoagulation. Correlation and regression analyses were used to examine relationships between dosing and time to therapeutic effect. Patients received an initial continuous infusion of 1450±462 units/h (range: 700 to 2700 units/h) or 13±4 units/kg/ h (range: 6 to 22 units/kg/h). Most study patients (64 patients, or 76.2%) received an initial infusion dosed more than 100 units/h below (in some cases, more than 1000 units/h below the recommended dose of 18 units/kg/h).
Duration	January 1, 2004 to December 31, 2006
Outcome Measures	Primary: Time to achievement of therapeutic anticoagulation (PTT >60 s) Secondary: Gap between recommended and prescribed heparin doses
Baseline Characteristics		All patients (n= 84)
	Female	48 (57.1%)
	Age, years (range)	57.1±17.8 (22 to 91)
	Median weight, kg (range)	105.5 (60 to 181)
	Median Body Mass Index, kg/m2 (range	36.6 (30.0 to 62.3)
	Pulmonary embolism Deep vein thrombosis	80 4
Results		All patients (n= 84)
	Time to achievement of PTT >60 s, h (IQR)	18.5 (8 to 41)
	Time to achievement of PTT >60 s >24 h	24 (28.6%)
	Time to achievement of PTT >60 s >48 h	12 (14.3%)
	Prescribed bolus dose below recommended	75 (89.3%)
	Initial continuous infusion below recommended	64 (76.2%)
Adverse Events	Not specified
Study Author Conclusions	A substantial proportion of obese patients treated with unfractionated heparin experienced a delay >24 h in achieving adequate anticoagulation, and the vast majority received an inadequate heparin bolus or initial continuous infusion (or both) according to current dosing guidelines.
Critique	The study highlights a significant issue of underdosing in obese patients with VTE, which may lead to delays in achieving therapeutic anticoagulation. However, the study is limited by its cross-sectional design and lack of post-discharge follow-up data to assess long-term outcomes such as recurrence or bleeding complications. Additionally, the study does not include a comparison group of non-obese patients, which could provide further insights into dosing practices across different BMI categories.

References:
[1] Hurewitz AN, Khan SU, Groth ML, Patrick PA, Brand DA. Dosing of unfractionated heparin in obese patients with venous thromboembolism. J Gen Intern Med. 2011;26(5):487-491. doi:10.1007/s11606-010-1551-2

Unfractionated heparin dosing for venous thromboembolism in morbidly obese patients: case report and review of the literature
Design	Case report
Case presentation	A 388-kg male suspected of having a pulmonary embolism, was initiated on heparin therapy following a hospital protocol that included a 5,000-unit heparin bolus followed by an infusion rate of 1,500 units per hour. Despite protocol adherence, therapeutic anticoagulation, as measured by activated partial thromboplastin time (aPTT), was significantly delayed. Adjustments eventually necessitated a heparin infusion rate of 3,650 units per hour to achieve the desired therapeutic level after 55 hours. During the treatment course, concerns about heparin-induced thrombocytopenia led to the discontinuation of heparin and initiation of fondaparinux, though heparin was resumed later due to ongoing hypoxemia and suspicion of recurrent pulmonary embolism. A therapeutic aPTT was achieved with a similar infusion rate of 3,550 units per hour during the second administration. However, the patient developed bloody pulmonary secretions while maintaining therapeutic aPTT values, prompting the cessation of heparin therapy once more. Unfortunately, due to subsequent complications, the patient died following an episode of pulseless electrical activity.
Study Author Conclusions	Despite limited data on heparin dosing in obesity, we recommend the use of a dosing weight to determine initial heparin dosing when treating venous thromboembolism in morbidly obese patients.

References:
[1] Myzienski AE, Lutz MF, Smythe MA. Unfractionated heparin dosing for venous thromboembolism in morbidly obese patients: case report and review of the literature. Pharmacotherapy. 2010;30(3):324. doi:10.1592/phco.30.3.324

Intravenous Unfractionated Heparin Dosing in Obese Patients Using Anti-Xa Levels
Design	Single-center, retrospective, observational cohort N= 131
Objective	To evaluate the efficacy and safety of a standard UFH protocol in obese patients using either adjusted body weight (ABW) or total body weight (TBW)
Study Groups	TBW (n= 67) ABW (n= 64)
Inclusion Criteria	Aged ≥ 18 years old; weighed ≥ 100 kg with a body mass index (BMI) ≥ 30 kg/m²; received intravenous UFH
Exclusion Criteria	Received an alternative UFH protocol; received less than 24 h of UFH based on the standard protocol; had inadequate compliance to protocol
Methods	The institution’s UFH protocol was used for titration based on UFH levels measured by anti-Xa levels (Initial bolus of 80 units/kg; initial infusion rate of 18 units/kg/h; anti-Xa level goal of 0.3–0.7 units/mL). Eligible patients were categorized based on TBW: 100–124.9 kg, 125–149.9 kg, and ≥ 150 kg for further analysis.
Duration	Data collection: January 1, 2013, to December 31, 2015
Outcome Measures	Primary: time to two consecutive therapeutic UFH levels as measured by anti-Xa levels (goal 0.3 to 0.7 units/mL) in patients dosed by TBW vs ABW Secondary: time to two consecutive therapeutic UFH levels in the three TBW weight categories, BMI classification, and whether a UFH bolus was given prior to the infusion
Baseline Characteristics		TBW (n= 67)	ABW (n= 64)	p-value
	Age, years	57.1 ± 12.4	51.5 ± 13.5	0.02
	Male	68.7%	71.9%	-
	BMI, kg/m²	41.5 ± 6.4	47.4 ± 8.8	< 0.0001
	Initial UFH infusion rate in units/kg/h	18 ± 2.8	12.5 ± 2.8	-
	Inpatient medications Warfarin Aspirin Clopidogrel	55.2% 46.3% 3.0%	35.9% 37.5% 0	0.04 0.38 0.50
Results	Endpoint	TBW (n= 67)	ABW (n= 64)	p-value
	Mean time to two therapeutic UFH levels, h	n= 59 29.4	n= 50 27.6	0.93
		100–124.9 kg (n= 33)	125–149.9 kg (n= 52)	≥150 kg (n= 24)	p-value
	Mean time to two therapeutic UFH levels based on TBW categories, h	29.3	27.5	29.9	0.80
		30-39.9 kg/m² (n= 36)	40-49.9 kg/m² (n= 50)	≥ 50 kg/m² (n= 23)	p-value
	Mean time to two therapeutic UFH levels based on BMI categories, h	30.5	25.0	33.4	0.09
		Bolus prior to infusion given (n= 42)	No bolus prior to infusion given (n= 89)	p-value
	Time to two consecutive therapeutic UFH levels < 24 h < 48 h < 72 h < 96 h Did not reach two consecutive therapeutic UFH levels	16 (38.1%) 10 (23.8%) 6 (14.3%) 3 (7.1%) 7 (16.7%)	42 (47.2%) 26 (29.2%) 6 (6.7%) 0 15 (16.9%)	0.02
Adverse Events	Common Adverse Events: overt bleeding events TBW vs. ABW (11.9% vs. 10.9%)
Adverse Events	Serious Adverse Events: major bleeding events (10.4% vs. 4.7%)
Study Author Conclusions	This study showed similar outcomes when dosing was based on either TBW or ABW. The findings of this study suggest no difference in reaching the primary outcome within 96 h for patients when based on either TBW or ABW. While ABW dosing results in a lower infusion rate compared to the higher rate of TBW, both dosing weight strategies were able to achieve therapeutic UFH levels at a similar rate.
InpharmD Researcher Critique	Given the retrospective design, the study is subject to selection bias. Moreover, this study derived data from a single institution with a relatively small number of patients using a specific dosing protocol which limits the generalizability of the results.

References:
[1] Ebied AM, Li T, Axelrod SF, Tam DJ, Chen Y. Intravenous unfractionated heparin dosing in obese patients using anti-Xa levels. J Thromb Thrombolysis. 2020;49(2):206-213. doi:10.1007/s11239-019-01942-6

Identifying Optimal Initial Infusion Rates for Unfractionated Heparin in Morbidly Obese Patients
Design	Prospective, observational cohort study N= 273
Objective	To better define appropriate UFH dosing strategies in morbidly obese patients and to evaluate the safety of a weight-based heparin nomogram in this patient population
Study Groups	Class III obesity (n= 94) Overweight/class I–II obesity (n= 92) Normal/underweight (n= 87)
Inclusion Criteria	Patients with class III (morbid) obesity receiving therapeutic doses of a UFH infusion for greater than 24 hours between September 2008 and March 2009
Exclusion Criteria	Patients with more than 1 significant deviation from the protocol, such as supratherapeutic or subtherapeutic aPTT without appropriate dosage titration
Methods	Patients were identified through a retrospective chart review from a single center in Missouri. A standardized order set was used to calculate an optimal bolus dose and initial infusion rate based on actual body weight. A nomogram guided aPTT monitoring and infusion rate adjustments. Data on dosing, aPTT values, bleeding, and mortality were collected.
Duration	September 2008 to March 2009
Outcome Measures	Primary: Mean infusion rate required to obtain a first therapeutic aPTT Secondary: Time to first therapeutic aPTT, mean infusion rate and time to obtain 2 consecutive therapeutic aPTTs, percentage of aPTT results within therapeutic ranges, clinically significant bleeding, in-hospital mortality
Baseline Characteristics		All Pts. (n = 273)	≥40 (n = 94)	25–39.9 (n = 92)	<25 (n = 87)
	Age, years	62.1 ± 15.8	54.6 ± 13.0	63.8 ± 15.7	68.5 ± 15.7
	Weight, kg	98.4 ± 39.5	141.3 ± 32.1	89.2 ± 15.6	61.8 ± 10.7
	BMI, kg/m2	33.7 ± 12.5	48.2 ± 8.1	30.5 ± 3.9	21.3 ± 2.5
	Male	132 (48.4%)	41 (43.6%)	45 (48.9%)	46 (52.9%)
	White	183 (67.0%)	56 (59.5%)	67 (72.8%)	60 (69.0%)
Results		≥40 (n = 94)	25–39.9 (n = 92)	<25 (n = 87)	p-value
	Mean infusion rate for first therapeutic aPTT, units/kg/h	11.5	12.5	13.5	0.001
	Mean time to first therapeutic aPTT, hours	21.3	22.1	30.0	0.421
	Mean infusion rate for 2 consecutive therapeutic aPTTs, units/kg/h	11.5	12.7	13.0	0.016
	Mean time to 2 consecutive therapeutic aPTTs, hours	38.8	36.6	39.3	0.776
	Clinically significant bleeding	5 (5.3%)	2 (2.2%)	3 (3.4%)	0.517
	In-hospital mortality	10 (10.6%)	6 (6.5%)	10 (11.5%)	0.475
Adverse Events	There was no significant difference in bleeding (p = 0.517) or mortality (p = 0.475) among groups
Study Author Conclusions	Morbidly obese patients require smaller UFH infusion rates per kilogram actual body weight compared to patients with lower body mass indices. UFH dosing recommendations should be modified to reflect body mass index classification.
Critique	The study is the largest to date addressing UFH dosing in morbidly obese patients, providing valuable insights into dosing strategies. However, it is limited by its observational design and inability to assess recurrence of thromboembolic events. The study may also be underpowered to detect differences in rare outcomes such as bleeding events. Additionally, the use of aPTT as a surrogate marker may not fully capture the anticoagulation status compared to anti-Xa levels.

References:
[1] Riney JN, Hollands JM, Smith JR, Deal EN. Identifying optimal initial infusion rates for unfractionated heparin in morbidly obese patients. Ann Pharmacother. 2010;44(7-8):1141-1151. doi:10.1345/aph.1P088

Safety and Efficacy of a High-Intensity, Weight-Based, Intravenous Heparin Protocol Revision in Patients Who Are Obese
Design	Retrospective chart review N= 55
Objective	To evaluate the safety and efficacy of the revised high-intensity, weight-based, intravenous heparin protocol in patients who are obese
Study Groups	Obese (greater than 50% above IBW, n= 10) Non-obese (less than 50% above IBW, n= 45)
Inclusion Criteria	All patients receiving high-intensity, weight-based heparin dosing from October 28, 2006, through March 15, 2007
Exclusion Criteria	Incomplete documentation; continuation of heparin therapy from an outside facility; transition from low-intensity or cardiovascular heparin protocols; violation of prespecified dosing guidelines; participation in a clinical trial
Methods	This was a retrospective chart review of patients receiving high-intensity, weight-based heparin protocol at a single center in Ohio. All patients received the high-intensity (goal aPTT 60 to 85 seconds, approximately 2 to 2.5 times control) weight-based IV heparin protocol. Patients were divided into obese and non-obese groups based on IBW. Primary outcomes included percentage achieving therapeutic aPTT, time to first therapeutic aPTT, and follow-up aPTT levels. Safety outcomes included adverse events and VTE recurrence.
Duration	October 28, 2006, through March 15, 2007
Outcome Measures	Primary: Percentage of patients achieving therapeutic aPTT, time to first therapeutic aPTT, follow-up aPTT levels Secondary: Occurrence of adverse events, recurrence of VTE, influence of concomitant disease states
Baseline Characteristics		Obese (n= 10)	Non-obese (n= 45)
	Age, years (mean ± SD)	60.9 ± 16.7	60.9 ± 16.7
	Female	55%	55%
	Previous PE/DVT	23.6%	23.6%
	CHF	20%	20%
	ESRD	14.5%	14.5%
Results		Obese (n= 10)	Non-obese (n= 45)	p-value
	Achieving therapeutic aPTT	80%	73.3%	0.971
	Time to first therapeutic aPTT, hours (median ± SD)	27.8 ± 27	31 ± 20.8	0.987
	Adverse events	0%	16.4%	0.193
Adverse Events	No adverse events were reported in the obese group. In the non-obese group, adverse events occurred in 16.4% of patients
Study Author Conclusions	The revised high-intensity, weight-based, IV heparin protocol is safe and effective for patients who are obese, validating a potential heparin dosing adjustment for this population.
Critique	The study's retrospective design and small sample size limit the generalizability of the findings. Additionally, the variability in data distribution and the lack of randomization or blinding may introduce bias. The study provides valuable insights into heparin dosing adjustments for obese patients, but further research with larger, randomized trials is needed to confirm these findings.

References:
[1] Dee BM, Thomas ML. Safety and efficacy of a high-intensity, weight-based, intravenous heparin protocol revision in patients who are obese. Hosp Pharm. 2008;43(11):895-902. doi:10.1310/hpj4311-895

Time to Target Anti-Xa Level in Obese Vs Nonobese Patients Using an Adjusted Body Weight Heparin Infusion Protocol for the Treatment of Venous Thromboembolism
Design	Single-center retrospective cohort study N= 166
Objective	To determine equivalency in time to reach target antifactor-Xa (anti-Xa) for obese and nonobese patients using the same adjusted body weight (AdjBW)-based unfractionated heparin (UFH) infusion protocol
Study Groups	Obese (n= 75) Nonobese (n= 91)
Inclusion Criteria	Patients aged 18 years or older treated with IV UFH for venous thromboembolism (VTE) for a minimum of 24 hours
Exclusion Criteria	Anticoagulant use prior to admission, thrombolytic administered prior to or during UFH treatment, UFH initiated at another institution, AdjBW not used for UFH dosing, pregnancy, or incarceration
Methods	Patients received an 80 unit/kg bolus followed by a maintenance infusion of 18 units/kg/h using AdjBW for dosing. Anti-Xa values were collected every 6 hours with nurse-driven dosing adjustments based on results for a goal anti-Xa range of 0.3 to 0.7 IU/mL
Duration	January 1, 2018, to December 31, 2023
Outcome Measures	Median time to first target anti-Xa, percentage of first anti-Xa levels at 6 hours within, below, or above target range
Baseline Characteristics		Obese (n= 75)	Nonobese (n= 91)
	Age, years	65 (54–73)	72 (60–83)
	Height, inches	66 (63–71)	67 (63–70)
	Weight, kg	104.5 (88.5–121.7)	66.7 (59.0–81.2)
	BMI, kg/m²	35.2 (32.2–41.3)	24.6 (21.3–26.7)
	Male	36 (48.00%)	44 (48.35%)
	White race	70 (94.59%)	88 (97.78%)
Results		Obese (n= 75)	Nonobese (n= 91)	p-value
	Median time to first target anti-Xa, hours	12.45	13.03	0.49
	First anti-Xa within target range	24 (32.00%)	31 (34.07%)	0.78
	First anti-Xa above target range	28 (37.33%)	42 (46.15%)	0.25
	First anti-Xa below target range	23 (30.67%)	18 (19.78%)	0.11
	Evidence of major bleed	6 (8.00%)	8 (8.89%)	0.84
Adverse Events	See Results
Study Author Conclusions	There was no observed difference in median time to first target anti-Xa in obese vs nonobese patients when using an AdjBW heparin infusion protocol, with no observed difference in evidence of major bleed. Our findings support the use of AdjBW in weight-based UFH dosing.
Critique	The study provides valuable insights into the use of AdjBW for UFH dosing in both obese and nonobese patients, demonstrating no significant differences in time to target anti-Xa or major bleeding events. However, the retrospective design and single-center setting may limit generalizability. Additionally, the lack of reporting on total heparin dose at target anti-Xa achievement poses challenges for extrapolation to other dosing protocols.

References:
[1] Eibye MK, Poston JN, Kennedy AG, DeSarno M, Nashett RM. Time to Target Anti-Xa Level in Obese Vs Nonobese Patients Using an Adjusted Body Weight Heparin Infusion Protocol for the Treatment of Venous Thromboembolism. Ann Pharmacother. 2025;59(11):1007-1014. doi:10.1177/10600280251321478

Evaluation of unfractionated heparin dosing using an antifactor-Xa-based protocol in non-obese vs. obese patients for acute venous thromboembolism
Design	Single-center, retrospective cohort study N= 172
Objective	To evaluate safety and efficacy outcomes of an antifactor-Xa based unfractionated heparin (UFH) venous thromboembolism (VTE) protocol in obese vs. non-obese patients
Study Groups	Non-obese (n= 99) Obese (n= 73)
Inclusion Criteria	Adults with a primary diagnosis of acute VTE treated with UFH according to institutional protocol between September 1, 2020 and September 1, 2023
Exclusion Criteria	Not receiving the initial bolus or infusion rate per protocol, dosing based on adjusted body weight, aPTT based monitoring, receipt of a direct oral anticoagulant or a therapeutic dose of a low molecular weight heparin within 72 hours, or factors influencing UFH pharmacokinetics
Methods	Patients received an initial bolus of 80 units/kg (max 10,000 units) and an initial infusion rate of 18 units/kg/hour based on total body weight. Anti-Xa levels were monitored to adjust UFH dosing. Data were collected retrospectively from electronic health records.
Duration	September 1, 2020 to September 1, 2023
Outcome Measures	Primary: Weight-based rate of UFH (units/kg/hr) required to attain a therapeutic anti-Xa level, rate required to attain steady state, time to first therapeutic anti-Xa level and steady state, proportion of anti-Xa levels being therapeutic, subtherapeutic, or supratherapeutic
Baseline Characteristics		Non-obese (n= 99)	Obese (n= 73)	p-value
	Age, years	66.3 ± 17.59	59.66 ± 15.91	0.01
	Female	48 (48.5%)	43 (58.9%)	0.23
	BMI, kg/m²	25.1 (21.9, 27.4)	35.8 (32.1, 42.7)	<0.0001
	VTE Diagnosis Type DVT PE DVT & PE	24 (24.2%) 45 (45.5%) 30 (30.3%)	14 (19.2%) 33 (45.2%) 26 (35.6%)	0.65
	VTE History	19 (19.2%)	24 (32.9%)	0.06
	Initial Bolus Dose Received, units/kg (IQR)	80 (80, 80)	80 (80, 80)	<0.0001
	Initial Bolus Dose Received, units (IQR)	5700 (4760, 6500)	8700 (7330, 9800)	<0.0001
Results		Non-obese (n= 99)	Obese (n= 73)	p-value
	UFH Rate at First Therapeutic anti-Xa level, (IQR) Units/kg/hour Units/hour	16 (14,18) 1133.6 (903.1, 1343.4)	14 (14,16) 1555.4 (1387.45, 1906.8)	<0.001 <0.0001
	UFH Rate at Steady State, (IQR) Units/kg/hour Units/hour	16 (14,18) 1142.4 (889, 1346.4)	14 (14,16) 1485.4 (1263.5, 1805.4)	<0.001 <0.0001
	Time to First Therapeutic anti-Xa level, hours	13.7 (8.1, 18.4)	11.7 (8.5, 18.1)	0.89
	Time to Steady State, hours	22.3 (15.1, 28.8)	23.2 (15.2, 31.5)	0.41
	Patients Attaining at Least One Therapeutic anti-Xa	96 (97.0%)	72 (98.6%)	0.84
	Patients Attaining Steady State	85 (85.9%)	59 (80.8%)	0.4
	Dose Changes Required to Attain Steady State	1 (0, 2)	1 (1, 2)	0.02
	Total Duration of Heparin Infusion, hours (IQR)	46.3 (37.3, 80.2)	47.3 (36.7, 79.2)	0.89
	First anti-Xa Level Therapeutic Subtherapeutic Supratherapeutic > 1.0 IU/mL	28 (28.3%) 8 (8.1%) 63 (63.6%) 32 (32.3%)	6 (8.2%) 1 (1.4%) 66 (90.4%) 57 (78.1%)	0.002 0.108 0.0001 <0.0001
	All anti-Xa Levels Within First 24 Hours, % (IQR) Therapeutic Supratherapeutic	50 (25, 70.5) 33 (0, 50)	33 (25, 50) 50 (33, 66)	0.02 <0.0001
	All anti-Xa levels for Duration of UFH Infusion, % (IQR) Therapeutic Supratherapeutic	62.5 (40, 75) 25 (6.07, 40)	50 (33.3, 62.5) 40 (29.4, 57.1)	0.001 <0.0001
	Met Major Bleed Criteria	23 (23.5%)	7 (9.6%)	0.03
	Any Bleed Criteria Met	28 (28.3%)	9 (12.3%)	0.03
Adverse Events	No significant differences in clinically overt bleeding rates were found. The non-obese group had a higher proportion of patients meeting major or any bleeding criteria, but this was mitigated when excluding patients with only a hemoglobin decrease ≥2g/dL.
Study Author Conclusions	Obese patients required a lower weight-based rate of UFH to attain therapeutic anti-Xa levels for the treatment of VTE. There appears to be an inverse relationship between weight-based UFH rate and total UFH rate at the first therapeutic anti-Xa and steady state as BMI increases. Future studies should focus on dosing strategies that improve attainment of therapeutic anti-Xa levels in obese patients.
Critique	The study's strengths include its large sample size and use of an anti-Xa based protocol, which provides a more precise measure of UFH activity. However, the retrospective design and single-center setting may limit the generalizability of the findings. The high incidence of PE compared to DVT may also affect the applicability of the results to broader populations. Additionally, the study did not assess overall mortality, only mortality due to fatal bleeding associated with heparin use.

References:
[1] Flanagan T, Sharma M, Cao UT, Wang X, Kataria V. Evaluation of unfractionated heparin dosing using an antifactor-Xa-based protocol in non-obese vs. obese patients for acute venous thromboembolism. J Thromb Thrombolysis. 2025;58(4):556-565. doi:10.1007/s11239-025-03097-z