Summary of Studies Using Weight-Based Dosing Therapeutic Unfractionated Heparin 

Citation

Design/population

Intervention

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)

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)

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).

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). 

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. 

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.

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).

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.

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.

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.

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.

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).

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.

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.

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)

Age, years

Male

BMI, kg/m²

Initial UFH infusion rate in units/kg/h

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

Mean time to two therapeutic UFH levels based on TBW categories, h

Mean time to two therapeutic UFH levels based on BMI categories,h

Bolus prior to infusion given

(n= 42)

No bolus prior to infusion given

(n= 89)

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%)

Adverse Events

Common Adverse Events: overt bleeding events TBW vs. ABW (11.9% vs. 10.9%) 

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.