What does the literature say regarding heparin infusion dosing in obese patients related to time to therapeutic aPTT, BMI threshold for using adjusted body weight, and safety?

Comment by InpharmD Researcher

While major guidelines are often ambiguous on the optimal weight descriptor for heparin dosing in obesity, clinical data supports the use of adjusted body weight. Some studies demonstrate that using adjusted body weight leads to a faster time to achieving therapeutic anticoagulation levels and reduces the rate of supratherapeutic levels compared to using total body weight. Furthermore, this approach has been associated with a reduced risk of clinically significant bleeding in obese patients. Still, other data are conflicting Additionally, current evidence does not define a maximum unfractionated heparin infusion rate for obese patients. Expert guidance recommends using weight-based dosing with total or adjusted body weight and adjusting the infusion based on institution-specific monitoring (e.g., aPTT or anti-Xa), rather than applying empiric dose caps, which may increase the risk of under-anticoagulation. Although therapeutic infusion requirements in obese patients have been reported to range from approximately 5 to 12.8 units/kg/hour, higher rates may be required to achieve target anticoagulation in some individuals. Overall, heparin infusion rates in obese patients should be individualized based on clinical response, laboratory monitoring, and institutional protocols.

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. Additionally, dosing recommendations for various body-mass index (BMI) categories are not provided. [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 current 2012 ACCP guidelines for the prevention of VTE in nonsurgical patients does not provide distinct recommendation on doses for patients who are obese. [5], [6]

A 2016 review provides guidance for the practical management of heparin anticoagulants in the treatment of thromboembolism. Two separate continuous infusion dosing regimens of heparin for the treatment of VTE are recommended: 1) 5,000 units bolus followed by 1,250-1,280 units/h or 2) 80 units/kg followed by 18 units/kg/h. It states that the two regimens have not been compared in a head-to-head trial, and individual institutions should monitor their own lab values to ensure patients are within the acceptable range. If the second regimen (weight-based) is selected, total body weight is recommended to calculate the dose. For obese/morbidly obese patients, either total body weight or adjusted body weight is recommended; however, if adjusted body weight is used, prompt attention to the initial laboratory results is suggested to ensure the therapeutic level is achieved in time. Finally, it suggests that an empiric dose cap may increase the risk of initial under-anticoagulation in obese and morbidly obese patients. In such cases, individual attention is recommended to ensure efficacy and safety. [7]

Another 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. [8]

Lastly, a 2018 review questioned the dosing of VTE prophylaxis as obesity rates are rising. 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. Problematically, 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. [9]

Background References: [1] Smythe MA, Priziola J, Dobesh PP, Wirth D, Cuker A, Wittkowsky AK. Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism. J Thromb Thrombolysis. 2016;41(1):165-186. doi:10.1007/s11239-015-1315-2
[2] Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e152S-e184S. doi:10.1378/chest.11-2295
[3] O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;61(4):e78-e140. doi:10.1016/j.jacc.2012.11.019
[4] Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published correction appears in J Am Coll Cardiol. 2014 Dec 23;64(24):2713-4. Dosage error in article text]. J Am Coll Cardiol. 2014;64(24):e139-e228. doi:10.1016/j.jacc.2014.09.017
[5] Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines [published correction appears in Chest. 2012 May;141(5):1369. Dosage error in article text] [published correction appears in Chest. 2013 Aug;144(2):721. Dosage error in article text]. Chest. 2012;141(2 Suppl):e24S-e43S. doi:10.1378/chest.11-2291
[6] Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e195S-e226S. doi:10.1378/chest.11-2296
[7] Smythe MA, Priziola J, Dobesh PP, Wirth D, Cuker A, Wittkowsky AK. Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism. J Thromb Thrombolysis. 2016;41(1):165-186. doi:10.1007/s11239-015-1315-2
[8] Vandiver JW, Ritz LI, Lalama JT. Chemical prophylaxis to prevent venous thromboembolism in morbid obesity: literature review and dosing recommendations. J Thromb Thrombolysis. 2016;41(3):475-481. doi:10.1007/s11239-015-1231-5
[9] Sebaaly J, Covert K. Enoxaparin Dosing at Extremes of Weight: Literature Review and Dosing Recommendations. Ann Pharmacother. 2018;52(9):898-909. doi:10.1177/1060028018768449
Literature Review

A search of the published medical literature revealed 13 studies investigating the researchable question:

What does the literature say regarding heparin infusion dosing in obese patients related to time to therapeutic aPTT, BMI threshold for using adjusted body weight, and safety?

Level of evidence

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


Please see Tables 1-13 for your response.

 

Utilization of adjusted body weight for dosing unfractionated heparin in obese patients with venous thromboembolism: A retrospective matched cohort study
Design

Retrospective matched cohort study

N= 57
Objective To evaluate the effectiveness of adjusted body weight (AjBW)-based dosing of unfractionated heparin (UFH) in obese patients vis a vis actual body weight (ABW)-based dosing in non-obese patients with venous thromboembolism (VTE)
Study Groups

Obese patients (n= 27)

Non-obese patients (n= 30)
Inclusion Criteria Obese and non-obese patients aged 18 years and older admitted with acute VTE from September 2013 to December 2014
Exclusion Criteria Patients under 18 years old, developed heparin-induced thrombocytopenia during treatment, received thrombolytic therapy prior to UFH, or received UFH at a dose that did not follow the institution’s protocol
Methods Retrospective chart review for patients who received intravenous infusion of UFH for VTE treatment. AjBW was used for dosing in obese patients, calculated as IBW + 0.3 (ABW - IBW). UFH dosing followed an internal protocol with a loading dose of 80 units/kg and an infusion rate of 15-18 units/kg/h to achieve a target aPTT of 74-106
Duration September 2013 to December 2014
Outcome Measures

Primary: Percentage of subjects achieving a therapeutic aPTT within the first 24 h

Secondary: Time to achieve therapeutic aPTT, number of supratherapeutic aPTT values, average number of UFH dose adjustments, number of bleeding or thrombotic events
Baseline Characteristics   Obese patients (n= 27) Non-obese patients (n= 30) P-value
Mean age (years) 62.18 ± 15.03 66.8 ± 13.95 0.231
Male 12 (44.44%) 17 (56.66%) 0.431
Female 15 (55.55%) 13 (43.33%) 0.431
Mean actual body weight (kg) 113.96 ± 20.36 73.07 ± 9.958 0.0001
Mean ideal body weight (kg) 61.98 ± 6.403 64.76 ± 6.19 0.119
Mean body mass index (kg/m2) 40.28 ± 7.045 25.08 ± 3.46 0.0002
Mean initial bolus dose (unit/kg) 79.44 ± 5.753* 79.07 ± 5.753ǂ 0.796
Mean initial infusion dose (unit/kg/h) 14.59 ± 1.474 14.40 ± 1.714 0.653
Results   Obese patients (n= 27) Non-obese patients (n= 30) P-value
Therapeutic aPTT within 24 h 16 (59%) 18 (60%) 0.45
Therapeutic aPTT > 24 to 48 h 26% 27% 0.59
Therapeutic aPTT after 48 h 15% 13% 0.46
Sub-therapeutic aPTT values 19% 17%  
Supratherapeutic aPTT values 22% 23%  
>1 Supratherapeutic aPTT value 78% 83%  
Adverse Events A total of six patients experienced bleeding (two in the obese group and four in the non-obese group). In the obese group, one patient experienced a minor nosebleed and one experienced minor hematochezia. In the non-obese group, two patients experienced gastrointestinal bleeding, and two patients experienced hematochezia. There were no thrombotic events in either group
Study Author Conclusions AjBW-based dosing of UFH in obese patients demonstrates comparable efficacy to ABW-based dosing in non-obese patients.
Critique The study's strengths include its focus on a relevant clinical question and the use of a matched cohort design. However, the small sample size and retrospective nature limit the generalizability of the findings. Further prospective studies with larger sample sizes are needed to confirm these results.

 

Table 1 References:
[10] Alessa M, Gramish J, Almodaimegh H, Khobrani MA, Hornsby L, Alhifany AA. Utilization of adjusted body weight for dosing unfractionated heparin in obese patients with venous thromboembolism: A retrospective matched cohort study. Tropical Journal of Pharmaceutical Research. 2021;20(1):191-195. doi:10.4314/tjpr.v20i1.27
Evaluation of unfractionated heparin therapy for venous thromboembolism using adjusted body weight in elderly or higher weight patients
Design

Single-center, retrospective, pre-post study

N= 80
Objective To determine if the use of adjusted body weight (AdjBW)-based unfractionated heparin (UFH) regimens improves time to therapeutic anti-Xa levels compared to total body weight (TBW)-based regimens in elderly or higher weight patients
Study Groups

TBW (n= 40)

AdjBW (n= 40)
Inclusion Criteria Patients aged ≥65 years or weighing ≥100 kg with suspected or confirmed VTE, admitted to Cooper University Hospital between July 1, 2019 and September 30, 2019 (TBW cohort) or July 1, 2021 and September 30, 2021 (AdjBW cohort)
Exclusion Criteria Significant variation from the approved heparin protocol, pregnant or incarcerated, received oral factor Xa inhibitor during or prior to admission, underwent extracorporeal membrane oxygenation during UFH infusion, missing height or height ≤152.4 cm
Methods Patients received UFH infusions dosed according to either TBW or AdjBW to target a therapeutic anti-Xa level. Anti-Xa assays were collected six hours after initiating the infusion, and infusion rates were adjusted to target a therapeutic anti-Xa goal of 0.3 to 0.7 units/mL. The study compared the time to therapeutic anti-Xa levels between the two dosing strategies
Duration July 1, 2019 to September 30, 2019 (TBW cohort) July 1, 2021 to September 30, 2021 (AdjBW cohort)
Outcome Measures

Primary: Median time to first therapeutic anti-Xa level

Secondary: Percentage of first-measured anti-Xa values in the therapeutic range, percentage of therapeutic anti-Xa values within the first 24 hours, inpatient mortality, major bleeding
Baseline Characteristics   TBW Cohort (n= 40) AdjBW Cohort (n= 40) p-value
Age in years - mean (SD) 68.8 (16.69) 67.3 (11.82) 0.64
TBW in kg - mean (SD) 91.02 (33.68) 84.76 (22.86) 0.33
Age ≥65 years only - no. (%) 27 (67.5) 27 (67.5) 1
Weight ≥100 kg only - no. (%) 11 (27.5) 11 (27.5) 1
Age ≥65 years and weight ≥100 kg - no. (%) 2 (5) 2 (5) 1
Received bolus dose of 80 units/kg - no. (%) 13 (32.5) 13 (32.5) 1
Male sex - no. (%) 19 (47.5) 20 (50) 0.82
Race, White (non-Hispanic) - no. (%) 25 (62.5) 27 (67.5) 0.64
Race, Hispanic - no. (%) 2 (5) 3 (7.5) 0.64
Race, African American - no. (%) 13 (32.5) 8 (20) 0.2
Race, Other - no. (%) 0 (0) 2 (5) 0.17
Location, Med/Surg Unit - no. (%) 29 (72.5) 27 (67.5) 0.63
Location, Intensive Care Unit - no. (%) 11 (27.5) 13 (32.5) 0.63
Concomitant antithrombotic medication used - no. (%) 25 (62.5) 34 (85) 0.02
Concomitant alteplase used - no. (%) 2 (5) 4 (10) 0.39
Serum creatinine - mean (SD) 1.24 (0.80) 1.56 (2.32) 0.42
Results   TBW Cohort (n= 40) AdjBW Cohort (n= 40) p-value
Median time to first therapeutic anti-Xa, hours (IQR) 20.9 (6.7–27.7) 13.6 (6.5–18.9) 0.02
Age ≥65 years only 21.9 (10.9–28.0) 13.6 (6.2–19.4) 0.026
Weight ≥100 kg only 13.9 (6.7–25.9) 11.2 (6.4–16.5) 0.47
Bolus at start of infusion 22.7 (17.4–27.6) 13.7 (12.3–15.0) 0.02
No bolus at start of infusion 20.9 (6.5–27.1) 13.5 (6.3–21.7) 0.21
First-measured anti-Xa within therapeutic range—no. (%) 12 (30) 17 (43) 0.24
Therapeutic anti-Xa values within the first 24 h of IV UFH protocol—no./total n(%) 40/103 (38.8) 59/105 (56.2) 0.01
In-hospital mortality—no. (%) 3 (7.5) 4 (10) 1
Major bleeds—no. (%) 4 (10) 2 (5) 0.68
Adverse Events No significant increase in major bleeding events between TBW and AdjBW groups (10% vs. 5%, p= 0.68)
Study Author Conclusions The use of adjusted body weight (AdjBW) for unfractionated heparin (UFH) dosing improves time to therapeutic anti-Xa levels in older adults and higher body weight patients, particularly in older adults. Larger, prospective studies are needed to determine the impact on clinical safety and efficacy outcomes.
Critique The study's retrospective, single-center design limits generalizability. The sample size for the weight subgroup was small, potentially underpowering the analysis. The study focused on laboratory outcomes rather than patient-centered endpoints. However, the study's real-life applicability and careful selection of time periods to avoid COVID-19-related coagulopathy are strengths. Larger, prospective trials are needed to confirm findings and assess clinical outcomes.
Table 2 References:
[11] Hopkins AJ, Chau T, Pullinger B, et al. Evaluation of unfractionated heparin therapy for venous thromboembolism using adjusted body weight in elderly or higher weight patients. J Thromb Thrombolysis. 2025;58(3):420-426. doi:10.1007/s11239-024-03060-4

 

Evaluation of heparin dosing based on adjusted body weight in obese patients
Design

Single-center retrospective cohort study

N= 393
Objective To determine whether heparin dosing based on adjusted body weight (BWAdj) instead of actual body weight (ABW) can lead to faster achievement of therapeutic activated partial thromboplastin time (aPTT) values in obese patients
Study Groups

Preimplementation obese (n= 76)

Preimplementation nonobese (n= 92)

Postimplementation obese (n= 77)

Postimplementation nonobese (n= 148)
Inclusion Criteria Patients 18 years or older; treated using the high-intensity heparin protocol with a targeted aPTT range of 68–95 seconds; had at least one aPTT measurement 6 hours after heparin infusion was started
Exclusion Criteria Pregnancy during heparin treatment, continuation of heparin therapy initiated at another institution, transition from low-intensity heparin therapy, receipt of subcutaneous low-dose heparin within the preceding 48 hours, receipt of other anticoagulants within 48 hours prior to initiation of heparin, and any violation of the high-intensity heparin protocol
Methods Retrospective cohort analysis comparing aPTT outcomes before and after implementation of a revised heparin protocol specifying BWAdj-based dosing for obese patients. BWAdj was calculated using the formula BWAdj = IBW + 0.4(ABW – IBW). Data were collected from medical records including demographic information, heparin dosing information, and aPTT values
Duration Preimplementation: January 2010–June 2011 Postimplementation: January 2013–July 2014
Outcome Measures

Primary: Percentage of first aPTT values within the target range after heparin initiation

Secondary: Median time to the first on-target aPTT, rate of clinically significant bleeding
Baseline Characteristics   Preimplementation Obese (n= 76) Preimplementation Nonobese (n= 92) Postimplementation Obese (n= 77) Postimplementation Nonobese (n= 148)
Mean ± S.D. age, yr 63.4 ± 15.6 64.0 ± 18.8 59.2 ± 11.7 67.3 ± 17.5
Male, no. (%) 32 (42.1) 51 (55.4) 48 (62.3) 81 (54.7)
Mean ± S.D. ABW, kg 104.7 ± 11.5 71.9 ± 15.2 138.7 ± 35.6 71.9 ± 14.9
Mean ± S.D. BMI, kg/m2 36.1 ± 8.1 24.1 ± 3.5 44.4 ± 10.4 24.4 ± 3.3
Results   Preimplementation Obese (n= 76) Preimplementation Nonobese (n= 92) Postimplementation Obese (n= 77) Postimplementation Nonobese (n= 148)
First aPTT within target range, no. (%) 8 (10.5) 14 (15.2) 13 (16.9) 31 (20.9)
Below target range, no. (%) 14 (18.4) 20 (21.7) 30 (39.0) 29 (19.6)
Above target range, no. (%) 54 (71.1) 58 (63.0) 34 (44.2) 88 (59.5)
Adverse Events Clinically significant bleeding was higher in obese patients preimplementation (11%) compared to nonobese (1%), but postimplementation rates did not differ significantly
Study Author Conclusions The percentages of first aPTT values in the targeted range did not differ significantly in obese and nonobese patients before and after protocol implementation. The use of BWAdj for dose calculation in obese patients was associated with faster achievement of an aPTT value in the target range
Critique The study provided valuable insights into heparin dosing in obese patients, showing faster achievement of target aPTT values with BWAdj-based dosing. However, the retrospective design and potential confounding factors such as differences in patient populations and institutional practices may limit the generalizability of the findings. Additionally, the study did not measure clinical outcomes associated with below-target aPTT values, which could be a concern for thrombosis risk
Table 3 References:
[12] 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

 

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%) 

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. 

 

 

Table 4 References:
[13] 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

 

Unfractionated heparin infusion for treatment of venous thromboembolism based on actual body weight without dose capping
Design

Single-center, retrospective cohort study

N= 423
Objective To compare time to first therapeutic activated partial thromboplastin time (aPTT) in hospitalized patients receiving UFH for acute venous thromboembolism (VTE) among three body mass index (BMI) cohorts: non-obese (< 30 kg/m2), obese (30–39.9 kg/m2), and morbidly obese (⩾ 40 kg/m2)
Study Groups

Non-obese (n= 230)

Obese (n= 146)

Morbidly obese (n= 47)
Inclusion Criteria Patients ⩾ 18 years of age, had a documented VTE, and were on an infusion of UFH for at least 24 hours
Exclusion Criteria Patients who did not authorize review of their medical records for research, received a thrombectomy, or received a fibrinolytic agent
Methods Patients received an optional 80 units/kg bolus of UFH followed by a continuous infusion starting at 18 units/kg/hour. Doses were calculated using actual body weight regardless of body size. The first aPTT was checked 6 hours following the infusion start. Further dose adjustments were made based on aPTT values using a nurse-driven protocol
Duration January 1, 2010 through December 31, 2016
Outcome Measures

Primary: Time to first therapeutic aPTT

 Secondary: Achievement of therapeutic, subtherapeutic, and supratherapeutic aPTT at 10 and 24 hours; bleeding and thrombotic complications
Baseline Characteristics   Non-obese (n= 230) Obese (n= 146) Morbidly obese (n= 47)
Age, years, mean (SD) 76.9 (12.7) 72.3 (11.1) 64.7 (11.5)
Male 108 (47.0%) 89 (61.0%) 26 (55.3%)
Charlson score, mean (SD) 5.1 (2.7) 5.0 (2.9) 3.5 (2.5)
Admission location - Floor 172 (74.8%) 104 (71.2%) 26 (55.3%)
Admission location - ICU 58 (25.2%) 42 (28.8%) 21 (44.7%)
Results   Non-obese (n= 230) Obese (n= 146) Morbidly obese (n= 47) p-value
Median time to therapeutic aPTT, hours 16.4 16.6 17.1 NS
Cumulative incidence of therapeutic aPTT within 24 hours 70.7% 69.9% 61.7% *See notes
Major bleeding events 14 (15%) 10 (18.6%) 3 (16.4%) NS
Subtherapeutic aPTT within 24 hours 43.9% 39% 17% <0.001
Supratherapeutic aPTT within 24 hours 42.2% 47.3% 61.7% 0.013
*Difference in cumulative incidence of therapeutic aPTT within 24 hours 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).
Adverse Events There was no significant difference in major bleeding events between BMI groups (obese vs non-obese, p = 0.91; morbidly obese vs non-obese, p = 0.98)
Study Author Conclusions Heparin dosing based on actual body weight without a dose cap is safe and effective for treating VTE in non-obese, obese, and morbidly obese patients. There were no differences in rates of bleeding among the groups.
Critique The study's retrospective design and smaller sample size for the morbidly obese group may limit the generalizability of the findings. Additionally, the study did not use ICD-9 and ICD-10 codes for bleeding or thrombotic complications, which may lead to underestimation of these events. Despite these limitations, the study provides valuable insights into the safety and efficacy of weight-based UFH dosing without a dose cap in different BMI cohorts.
Table 5 References:
[14] 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

 

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.

 

Table 6 References:
[15] 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

 

Unfractionated heparin dosing in obese patients
Design

Retrospective audit

N= 200
Objective To determine if current practices for unfractionated heparin dosing leads to inadequate anticoagulation in obese patients
Study Groups

<100 kg (n= 34)

100–124.9 kg (n= 122)

125–150 kg (n= 27)

>150 kg (n= 17)
Inclusion Criteria Patients who received IV UFH according to the hospital nomogram
Exclusion Criteria Patients receiving prophylactic doses of UFH, a target APTT outside the nomogram ranges, patients prescribed UFH for dialysis, patients with limited data available (<2 APTTs), and patients with genetic prothrombotic disorders
Methods

A retrospective chart review was conducted from January to July 2018 at the Princess Alexandra Hospital. Patients were identified through electronic reports. Data collected included doses administered and subsequent APTT levels taken approximately 4–6 hours later. Patients were grouped into four weight cohorts. 

Obesity was described as a weight > 100 kg. Actual body weight was used for dosing UFH.
Duration January to July 2018
Outcome Measures

Primary: Mean maintenance doses in U/h and U/kg/h required to achieve two consecutive therapeutic APTTs

Secondary: Median infusion time to achieve two consecutive therapeutic APTTs
Baseline Characteristics   < 100 kg (n= 34) 100–124.9 kg (n= 122) 125–150 kg (n= 27) > 150 kg (n= 17)
Weight (kg) 76 ± 13.6 109.7 ± 7.8 133.2 ± 8.5 188.2 ± 35.9
Age (years) 64.9 ± 13.9 61 ± 11.4 56 ± 12 57 ± 12
Male, n (%) 18 (52.9) 93 (76.2) 18 (66.7) 9 (52.9)
Current smoker, n (%) 6 (17.6) 29 (23.8) 6 (22.2) 2 (11.8)
ICU patient, n (%) 1 (2.9) 31 (25.4) 8 (29.6) 10 (58.8)
BMI (kg/m2) 27.2 ± 5.5 36.6 ± 5.1 44.2 ± 4.7 63.5 ± 14.3
Results   < 100 kg (n= 34) 100–124.9 kg (n= 122) 125–150 kg (n= 27) > 150 kg (n= 17)
Mean maintenance dose (U/h) 1229 ± 316 1673 ± 523 2031 ± 596 2146 ± 846
Mean maintenance dose (U/kg/h) 16 ± 4.1 15.1 ± 4.8 14.9 ± 4.2 11.6 ± 4.2
Median time to therapeutic APTTs (h) 47 (23–77.5) 39 (21.5–56) 39 (21.5–56) 39 (21.5–56)
Adverse Events There were 27 patients (13.5%) with reported cases of bleeding and 15 patients (7.5%) died during their admission. The rates of bleeding between non-obese and obese cohorts were non-significant (p= 0.302)
Study Author Conclusions Larger absolute doses (U/h) of IV UFH but reduced uncapped TBW based doses (U/kg/h) should be considered in obese patients. Further prospective randomised controlled studies are required.
Critique The study was limited by its single site retrospective design, which may be prone to documentation or recording errors. The small sample size in the <100 kg and >150 kg cohorts made comparative analyses difficult. Additionally, the study did not control for factors that may influence APTT readings, such as sample haemolysis or increased UFH binding proteins. Despite these limitations, the study supports findings that absolute infusion dose requirements increase with weight, while TBW based doses decrease.
Table 7 References:
[16] 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

 

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.

 

Table 8 References:
[17] 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

 

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 admitted for NSTEMI/UA or atrial fibrillation, or other cardiac indications and received at least 6 hours of a continuous UFH infusion
Exclusion Criteria Patients who experienced deviations from either dosing strategy, including changes to aPTT goals and altered initial infusion rates; UFH infusion interrupted before at least one aPTT was measured
Methods

Patients received either standard UFH dosing (60-unit/kg bolus [or maximum 4000 units] followed by an infusion of 12 units/kg/hour [or maximum 1000 units/hour]) or aggressive UFH dosing (60-unit/kg bolus [or maximum 10,000 units] followed by an infusion of 12 units/kg/hour [or maximum 2250 units/hour]). UFH dosing was calculated based on patient's actual body weight. 

Time-to-event analysis for achievement of therapeutic aPTT range (60–80 sec) was assessed. Data were collected from electronic medical records.
Duration

Standard dosing: September 2013 to February 2014

Aggressive dosing: October 2014 to March 2015
Outcome Measures

Primary: Achievement of therapeutic aPTT value within 6 hours

Secondary: Time required to obtain a therapeutic aPTT value, incidence of supratherapeutic aPTT values, number of additional UFH bolus doses required for subtherapeutic aPTT value 
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, small sample size, and single-center setting, which may affect the generalizability of the findings. The potential for incomplete documentation in a retrospective chart review may have led to underreporting of clinically relevant 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 are needed to determine optimal UFH dosing regimens for patients with cardiovascular indications.
Table 9 References:
[18] 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

Adjusted Versus Total Body Weight Dosing for Intravenous Heparin Infusions and Target Attainment in Obese Patients
Design

Single center, retrospective cohort study

N= 477
Objective To evaluate the achievement of therapeutic heparin correlation values (HCV) with heparin infusions dosed utilizing total body weight (TBW) versus adjusted body weight (ABW) in obese patients
Study Groups

TBW cohort (n= 453)

ABW cohort (n= 24)
Inclusion Criteria Obese patients (BMI ≥30 kg/m2), at least 18 years of age, initiated on and receiving a continuous IV heparin infusion following a standard nomogram for at least 6 hours, admitted between January 1, 2020, to May 20, 2023
Exclusion Criteria Prolonged aPTT at baseline (>40 seconds), heparin infusion initiated at an outside institution, history of genetic prothrombotic disorders, use of additional anticoagulants at the time of the heparin infusion, and active pregnancy
Methods A standard weight-based institutional nomogram for heparin monitoring and dose adjustment was followed. Heparin monitoring was based on HCV, with an initial level checked 6 hours after initiation of the heparin infusion. Data was collected from electronic medical records
Duration January 1, 2020, to May 20, 2023
Outcome Measures

Primary: Percentage of initial HCV within the therapeutic range after heparin initiation

Secondary: Incidence of supratherapeutic HCV at any time, major bleeding events
Baseline Characteristics   Total body weight (n= 453) Adjusted body weight (n= 24) P-value
Age, years (mean ± SD) 56.4 ± 14.7 51.6 ± 14.7 .120
Male sex, n (%) 222 (49) 13 (54.2) .622
BMI, kg/m2 (mean ± SD) 36.8 ± 7.4 42.1 ± 9.3 <.001
Class 1: BMI 30-<35, n (%) 237 (52.3) 6 (25) .009
Class 2: BMI 35-40, n (%) 125 (27.6) 5 (20.8) .469
Class 3: BMI ≥40, n (%) 91 (20.1) 13 (54.2) <.001
Results   Total body weight (n= 453) Adjusted body weight (n= 24) P-value
First HCV therapeutic, n (%) 190 (41.9) 13 (54.2) .238
Supratherapeutic HCV during therapy, n (%) 293 (64.7) 10 (41.7) .022
Major bleeding, n (%) 69 (15.2) 3 (12.5) .716
Adverse Events Major bleeding occurred in 15.2% of patients in the TBW cohort and 12.5% in the ABW cohort
Study Author Conclusions Utilization of ABW compared to TBW for dosing of heparin infusions in obese patients did not lead to a higher attainment of therapeutic anticoagulation at the first monitoring timepoint. Increased rates of supratherapeutic levels of anticoagulation in obese patients dosed based on TBW warrant consideration of empiric dose adjustment in this patient population.
Critique The study is limited by its small sample size and retrospective nature, which may introduce selection bias. The single-center design and specific heparin order set and nomogram used may limit generalizability. The study did not address efficacy endpoints or evaluate all possible risk factors for bleeding or VTE development.
Table 10 References:
[19] Nguyen K, Murray B, Campbell-Bright S, et al. Adjusted Versus Total Body Weight Dosing for Intravenous Heparin Infusions and Target Attainment in Obese Patients. Hosp Pharm. Published online June 29, 2025. doi:10.1177/00185787251348377

 

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.

 

Table 11 References:
[20] 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

 

Limitations of a standardized weight-based nomogram for heparin dosing in patients with morbid obesity
Design

Retrospective study

 N= 101
Objective To compare the activated partial thromboplastin time (aPTT) values in morbidly obese and nonmorbidly obese patients using a standardized nomogram and to determine factors associated with achieving a supratherapeutic aPTT value
Study Groups

Morbidly obese (n= 38)

Nonmorbidly obese (n= 63)
Inclusion Criteria Patients who received intravenous heparin according to a standardized weight-based nomogram for ≥12 hours
Exclusion Criteria Age <18 years, pregnancy, and insufficient data
Methods

Patients were stratified into morbidly obese (BMI ≥40 kg/m2) and nonmorbidly obese (BMI <40 kg/m2) groups. Heparin was administered using a high-intensity, weight-based nomogram with an 80-U/kg bolus followed by an 18-U/kg/hr infusion rate. aPTT measurements were obtained at 6-hour intervals.

All heparin doses were calculated based on actual body weight. No dose cap or maximal bolus was used. The institution-specific therapeutic range for activated partial thromboplastin time aPTT value was 70–110 seconds.
Duration December 2004 to December 2005
Outcome Measures

Primary: aPTT values at 6 and 12 hours

Secondary: Predictors of supratherapeutic aPTT values
Baseline Characteristics   Morbidly obese patients (n= 38) Nonmorbidly obese patients (n= 63) P value
Actual body weight (kg) 151 ± 43 97 ± 25 <.001
Ideal body weight (kg) 62 ± 13 70 ± 13 .007
Height (in.) 67 ± 5 69 ± 5 .007
BMI (kg/m2) 52.5 ± 12.1 31 ± 5.7 <.001
Received bolus (%) 79 95 .018
Bolus dose (U/kg) 70 ± 17 79 ± 3 .012
Initial infusion rate (U/kg/hr) 17 ± 1.6 18 ± 0.5 .336
Results   Morbidly obese patients Nonmorbidly obese patients P value
Baseline aPTT 32 ± 7 28 ± 4 .016
aPTT (first assessment) 155 ± 37 135 ± 44 .020
aPTT (second assessment) 141 ± 45 117 ± 45 .012
Adverse Events Four patients had a bleeding event during the evaluation period. Only 2 patients had a supratherapeutic aPTT value.
Study Author Conclusions Heparin dosing with a weight-based nomogram will yield greater aPTT values in morbidly obese patients. Consideration of BMI and age can help identify those patients at risk of supratherapeutic aPTTs. Alternative strategies, such as a dose cap should be considered in patients with morbid obesity.
Critique The study was limited by its retrospective nature and potential confounding factors such as baseline aPTT differences and fewer obese patients receiving a bolus dose. The study was likely underpowered to detect bleeding events. Future prospective trials are necessary to validate the findings.
Table 12 References:
[21] 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

 

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.

 

Table 13 References:
[22] 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