What literature supports a maximum dose of unfractionated heparin in patients with obesity?

Introduction
Standard therapeutic dosing for unfractionated heparin is weight-based (80 units/kg bolus followed by 18 units/kg/hour infusion), which raises concern for appropriate dosing in patients with obesity.1 Using actual body weight when calculating the dose could increase bleeding risk but using ideal or adjusted body weights could lead to underdosing. Since both approaches are limited, and since venous thromboembolism (VTE) treatment guidelines do not comment on unfractionated heparin dosing in patients with obesity, a third strategy of using a maximum dose has been explored.2,3

Literature Review
A search of the primary literature did not reveal any randomized studies of heparin dosing in patients with obesity. The available literature (summarized in the Table) is limited by its observational/retrospective nature and generally small sample sizes.4-21 The small sample sizes affect interpretation of both efficacy and safety results; none of the studies in the Table reported a difference in bleeding between groups, likely due to lack of power to detect differences in this outcome. Other limitations include differences among studies in initial heparin doses and target anti-factor Xa or activated partial thromboplastin time (aPTT) values.

In studies that dosed based on total body weight without dose capping, no differences were reported in time to therapeutic aPTT levels (or achievement of therapeutic aPTT levels at a designated time point) between patients with and without obesity.6,8,11,12,15,16,18-20

One study suggested that lower infusion rates were needed in patients with obesity, which has also been reported in the setting of percutaneous coronary intervention.11,22 Two studies that used dose capping also suggested that patients with higher weights required lower doses to achieve therapeutic anticoagulation.7,13 However, other studies that used dose capping had conflicting results about the appropriateness of dose capping.9,10,14

Studies that dosed based on adjusted body weight with no capping did not demonstrate a benefit of using an adjusted body weight rather than total body weight.4-6,12,21

Table. Studies investigating maximum doses of unfractionated heparin in patients with obesity.4-21
StudyPatient populationInterventionsaResults
Eibye et al 20254166 adults with VTE, with and without obesity

Retrospective, single-center study		UFH dosed on adjusted body weight
Doses were not capped		Median time to first target anti-Xa level was similar between patients with and without obesity (about 13 hours; p=0.49)
Tyler et al 2023532 adults with obesity with VTE

Retrospective, single-center study		UFH dosed on total body weight
UFH dosed on adjusted body weight
Doses were not capped		Time to first therapeutic anti-Xa level was similar between dosing weight groups (about 15 hours; p=0.613)
Ebied et al 20206131 adults with obesity

Retrospective, single-center cohort study		UFH dosed on total body weight
UFH dosed on adjusted body weight (for patients >125 kg)
Doses were not capped		Median time to 2 consecutive target anti-Xa levels was similar between groups (30 hours for total body weight, 25 hours for adjusted body weight; p=0.09)
George et al 20207200 patients with obesity who received UFH for ACS, VTE, or bridging therapy

Retrospective, single-center study		UFH dosed on total body weight
Bolus doses were capped at 8000 units
Infusion doses were capped at 1500 units/hr		Capped doses led to more patients requiring infusion doses above the initial cap recommendation to achieve therapeutic aPTT compared to patients weighing <100 kg (p=0.0047)

Dose required to achieve 2 consecutive therapeutic aPTT:
<100 kg: 16 units/kg/hr
100 to 124.9 kg: 15.1 units/kg/hr
125 to 150 kg: 14.9 units/kg/hr
>150 kg: 11.6 units/kg/hr
Shlensky et al 20208423 adults with VTE, with and without obesity

Retrospective cohort study		UFH dosed on total body weight
Doses were not capped
Only about 60% of patients received a bolus dose		Time to therapeutic aPTT was not significantly different between patients with obesity, morbid obesity, and without obesity (about 16.5 hours; p-value not given)
Floroff et al 20179197 adults with and without obesity

Retrospective, before/after cohort study		UFH dosed on total body weightb
Standard dosing (historical):
Bolus doses were capped at 4000 units
Infusion doses were capped at 1000 units/hr
Aggressive dosing (intervention):
Bolus doses were capped at 10,000 units
Infusion doses were capped at 2250 units/hr (aggressive dosing)		Therapeutic aPTT within 6 hours was more common with aggressive dosing (23%) than with standard dosing (11%; p=0.034)

Median time to therapeutic aPTT was shorter with aggressive dosing (15 hours) versus standard dosing (21 hours; p=0.036)
Hosch et al 201710298 patients with VTE, with and without obesity

Retrospective cohort study		UFH dosed on total body weight
UFH dosed on dosing body weight (if total body weight was ≥120% of ideal body weight)
Bolus doses were capped at 10,000 units
Infusion doses were capped at 2500 units/hr

Dosing body weight=ideal body weight + [(0.4)(actual body weight - ideal body weight)]		Time to therapeutic aPTT was not significantly different between patients with obesity, severe obesity, and without obesity (about 15 hours; p=0.506)
Isherwood et al 201711296 adults, with and without obesity

Retrospective cohort study		UFH dosed on total body weight
Doses were not capped
High, moderate, and low anti-Xa levels were targeted		Patients with obesity required lower infusion rates to achieve target anti-Xa levels compared to patients without obesity (high and moderate anti-Xa targets only; p<0.001 and p=0.003, respectively)
Fan et al 201612393 patients with and without obesity

Retrospective, single-center cohort study		UFH dosed on total body weight
UFH dosed on adjusted body weight
Doses were not capped		Time to first therapeutic aPTT was not significantly different between patients with and without obesity (14 to 17 hours; p=0.47)

Patients with obesity achieved therapeutic aPTT faster when dosed on adjusted body weight versus total body weight (p=0.002)
Hohner et al 201513206 critically ill patients (normal weight [95 to 104 kg], high weight [105 to 129 kg], and higher weight [≥130 kg])

Retrospective, single-center cohort study		UFH dosed on total body weightc
Standard nomogram (patients ≥105 kg):
Bolus doses were capped at 7700 units
Infusion doses were capped at 1650 units/hr

Low dose nomogram (patients ≥105 kg):
Bolus doses were capped at 6600 units
Infusion doses were capped at 1300 units/hr		Time to therapeutic aPTT was not significantly different between groups (controls, high weight, and higher weight) (about 28 hours; p=0.99)

Dose required to achieve therapeutic aPTT (p=0.009):
Controls: 15.8 units/kg/hr
High weight: 15.5 units/kg/hr
Higher weight: 13.1 units/kg/hr
Shin et al 201514240 patients with and without obesity

Retrospective cohort study		UFH dosed on total body weight Bolus doses were not capped
Infusion doses were capped at 1800 units/hr for VTE or 1100 units/hr for ACS		Mean time to first therapeutic aPTT (p=0.002):
<100 kg: about 13 hours
100 to 124.9 kg: about 15.5 hours
125 to 150 kg: about 18 hours
>150 kg: about 24 hours

Dose required to achieve therapeutic aPTT (p<0.001):
<100 kg: 16 units/kg/hr
100 to 124.9 kg: 14.6 units/kg/hr
125 to 150 kg: 13.0 units/kg/hr
>150 kg: 11.3 units/kg/hr
Gerlach et al 20131562 critically ill patients with and without obesity

Retrospective cohort study		UFH dosed on total body weightd
Bolus doses were not used
Infusion doses were not capped		Mean time to therapeutic aPTT was not significantly different between obesity levels (about 17 to 20 hours; p=0.54)
Taylor et al 20131650 children, with and without obesity

Retrospective, single-center case-control study		UFH dosed on total body weight
Infusion dose cap of 1000 units/hr was suggested
Only about 50% of patients received a bolus dose		Mean time to 2 consecutive target anti-Xa levels was lower in patients with obesity (about 27 hours) compared to patients without obesity (about 44 hours; p=0.045)

Patients with obesity required lower mean initial (p=0.013) and maintenance doses (p=0.033) to achieve therapeutic aPTT or anti-Xa levels compared to patients without obesity
Riney et al 201017285 patients with and without obesity

Prospective observational cohort study		UFH dosed on total body weight Bolus doses were only capped for patients with ACS – 4000 units
Infusion doses were not capped		Time to therapeutic aPTT was not significantly different between obesity levels (about 21 to 30 hours; p=0.421)

Supratherapeutic aPTT was more common among higher BMIs (p=0.008)
Bauer et al 2009181054 patients, with and without obesity

Retrospective, single center cohort study		UFH dosed on total body weightb
Doses were not capped		Proportion of first aPTT values in goal range was not statistically different between patients with and without obesity (about 30% to 35%; p=0.07)
Barletta et al 200819101 patients, with or without morbid obesity

Retrospective cohort study		UFH dosed on total body weight
Doses were not capped		At 12 hours, significantly more patients without morbid obesity (43%) had a therapeutic aPTT compared to patients with morbid obesity (18%; p=0.012)
Spruill et al 20012040 patients, with or without obesity

Retrospective cohort study		UFH dosed on total body weighte
Doses were not capped		Time to therapeutic aPTT was not significantly different between patients with and without obesity (25 hours; p-value not given)
Yee and Norton 199821213 adults, with or without obesity

Retrospective cohort study		UFH dosed on total body weight (patients without obesity)
UFH dosed on adjusted body weight (patients with obesity)
Doses were not capped		Mean initial aPTT was significantly lower in patients with obesity than in patients without obesity
Abbreviations: ACS=acute coronary syndrome; aPTT=activated partial thromboplastin time; BMI=body mass index; UFH=unfractionated heparin; VTE=venous thromboembolism.
a UFH was dosed at 80 units/kg bolus and 18 units/kg/hr infusion unless otherwise specified.
b UFH was dosed at 60 units/kg bolus and 12 units/kg/hr infusion.
c UFH was dosed at 60 or 70 units/kg bolus and 12 or 15 units/kg/hr infusion.
d UFH was dosed at 16 units/kg/hr for patients with obesity and 12 units/kg/hr for patients with morbid obesity.
e UFH was dosed at 70 units/kg bolus and 15 units/kg/hr infusion.

Conclusions
Studies addressing the question of the most appropriate dosing weight and/or whether dose capping should be used for unfractionated heparin in the treatment of VTE are limited. Almost all of the data is retrospective, and sample sizes are too small to detect differences in bleeding. Overall, the studies that examined dose capping do not suggest that capped doses improve time to therapeutic anticoagulation compared to uncapped doses. The available literature supports using total body weight as the dosing weight, but further prospective study is needed. Clinicians should continue to use caution and close monitoring when using unfractionated heparin in patients with obesity.

References

  1. Clinical Pharmacology. Elsevier; 2025. Accessed March 24, 2025. https://www-clinicalkey-com
  2. Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018;2(22):3257-3291. doi:10.1182/bloodadvances.2018024893
  3. Stevens SM, Woller SC, Kreuziger LB, et al. Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report. Chest. 2021;160(6):e545-e608. doi:10.1016/j.chest.2021.07.055
  4. 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. Published online March 21, 2025. doi:10.1177/10600280251321478
  5. Tyler DJ, Caruso KA, Lyden AE, Karpowitsch KM. Emergency department management of acute venous thromboembolism in patients with obesity with intravenous unfractionated heparin and anti-Xa monitoring. J Pharm Pract. 2023;36(3):588-593. doi:10.1177/08971900221074935
  6. 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
  7. 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
  8. 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
  9. Florof 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. 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. 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
  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
  13. Hohner EM, Kruer RM, Gilmore VT, Streif 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
  14. 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 Coag Fibrinol. 2015;26(6):655-660. doi:10.1097/MBC.0000000000000336
  15. 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 Injury Sci. 2013;3(3):195-199. doi:10.4103/2229-5151.119200
  16. Taylor BN, Bork SJ, Kim S, Moffett BS, Yee DL. Evaluation of weight-based dosing of unfractionated heparin in obese children. J Pediatr. 2013;163(1):150-153. doi:10.1016/j.jpeds.2012.12.095
  17. 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. https://doi.org/10.1345/aph.1P088
  18. Bauer SR, Ou NN, Dreesman BJ, et al. Effect of body mass index on bleeding frequency and activated partial thromboplastin time in weight-based dosing of unfractionated heparin: a retrospective cohort study. Mayo Clin Proc. 2009;84(12):1073-1078. doi:10.4065/mcp.2009.0220
  19. 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
  20. Spruill WJ, Wade WE, Huckaby WG, Leslie RB. Achievement of anticoagulation by using a weight-based heparin dosing protocol for obese and nonobese patients. Am J Health-Syst Pharm. 2001;58(22):2143-2146. doi:10.1093/ajhp/58.22.2143
  21. Yee WP, Norton LL. Optimal weight base for a weight-based heparin dosing protocol. Am J Health-Syst Pharm. 1998;55(2):159-162. doi:10.1093/ajhp/55.2.159
  22. Kreutz RP, Leon IG, Bain ER, et al. Heparin Dosing During Percutaneous Coronary Intervention and Obesity. J Cardiovasc Pharmacol. 2024;83(3):251-257. doi:10.1097/FJC.0000000000001525

Prepared by:
Heather Ipema, PharmD, BCPS
University of Illinois Chicago Retzky College of Pharmacy

April 2025

The information presented is current as of March 22, 2025. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.