What heparin infusion weight cap does literature support? Are there different weight caps based on indication? And is there literature to support heparin no sub-therapeutic bolus infusion protocols?

Comment by InpharmD Researcher

Current literature does not appear to support a specific evidence-based weight cap for heparin infusions. Both the 2026 ISTH guidance and a 2016 guidance recommend weight-based (generally total body weight) dosing without an established maximum, noting that empiric dose caps may cause initial under-anticoagulation in obese patients, though data are lacking above ~270 kg. While dosing intensity and aPTT/anti-Xa targets vary by indication (e.g., ACS, VTE, mechanical-valve bridging), the literature does not establish separate maximum dosing weights by indication. Evidence also does not support a routine no-bolus protocol. Bolus-inclusive nomograms improve time to therapeutic anticoagulation and reduce recurrent VTE in standard treatment; but no-bolus strategies have shown benefit in select populations (e.g., fewer bleeding events in ECMO patients and safety of low-dose or omitted boluses in TIA/stroke). Therefore, no single bolus versus no-bolus strategy can be broadly recommended.
Background

Guidance published in 2026 by the International Society on Thrombosis and Haemostasis (ISTH) was developed to summarize the limited available evidence and provide consensus recommendations for the monitoring, initiation, and dose adjustment of therapeutic unfractionated heparin. The guidance does not identify an evidence-based maximum patient-weight cap for heparin infusion dosing and specifically defers recommendations for special populations, including patients with obesity, to subsequent guidance. It recommends using a weight-based nomogram but concludes that available evidence is insufficient to favor one nomogram or dosing cap over another. Although a retrospective study in patients with mechanical mitral valves used maximum initial infusion rates of 1,000 units/hour for a low-intensity regimen and 1,800 units/hour for a high-intensity regimen, the study was not powered to detect differences in thrombotic or bleeding outcomes; therefore, these limits should not be interpreted as broadly supported weight caps. [1]

Furthermore, the guidance describes different dosing intensities and targets according to indication, including acute coronary syndrome (ACS) and mechanical-valve bridging, but it does not establish separate maximum dosing weights for different indications. Regarding subtherapeutic anticoagulation, the paper does not provide evidence supporting a routine no-bolus protocol. Instead, it suggests a weight-based nomogram that includes an initial bolus and subsequent dose adjustments; the cited randomized trial found that initial and repeated boluses as needed improved attainment of therapeutic anticoagulation within 24 hours and were associated with fewer recurrent venous thromboembolic events than standard care. However, because published nomograms differ in their use of boluses and none have been validated using clinical events as the primary outcome, the guidance cannot recommend one specific bolus or no-bolus adjustment strategy over another. [1]

A 2016 guidance document notes that current heparin dosing recommendations do not specify which body weight should be used for weight-based dosing. The authors also note that the original Raschke nomogram was developed using actual body weight, although only 9 of 115 patients (<8%) weighed more than 100 kg (range 101–131 kg). Because available evidence is limited by low-quality studies, heterogeneous dosing strategies, and small sample sizes, the guidance suggests using total body weight when a weight-based dosing strategy is selected, while either total body weight or adjusted body weight may be used in obese or morbidly obese patients with close monitoring of anticoagulation parameters. The guidance cautions that empiric dose caps may increase the risk of initial under-anticoagulation in obese patients and recommends individualized dosing if dose caps are used. Although no increased risk of major bleeding has been reported with total body weight-based dosing in morbidly obese patients, available studies have not included patients weighing >270 kg. [2]

A 2022 literature review of PubMed studies addressed three questions on UFH bolus use: the function and therapeutic-range goals of an initial bolus, and the risks of subtherapeutic and supratherapeutic activated partial thromboplastin time (aPTT). It was determined that patients already anticoagulated should not receive an initial UFH bolus, while non-anticoagulated patients benefit from a bolus based on indication (e.g., 80 units/kg then 18 units/kg/hr for VTE), reaching therapeutic aPTT roughly 60 minutes sooner than without a bolus (9.6±7.3 vs 14.5±10.8 hours). However, neither group showed a significantly greater likelihood of achieving or maintaining therapeutic aPTT range overall. Subtherapeutic aPTT was linked to 20–25% VTE recurrence, while each 10-second aPTT increase above the prespecified goal range raised major bleeding risk by roughly 7%. As a non-systematic, single-institution literature synthesis without original patient-level data or a defined selection methodology, its conclusions are best viewed as a practical clinical summary rather than high-grade evidence. Additionally, this study was available only as a published conference abstract; as such, the full results were not able to be independently verified. [3]

Background References: [1] Gouin-Thibault I, Frere C, Castellucci LA, et al. How to monitor and manage unfractionated heparin in practice (Part 1)? Guidance from the SSC of the ISTH. J Thromb Haemost. Published online May 20, 2026. doi:10.1016/j.jtha.2026.05.013
[2] 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
[3] Gechlik A, Espinosa J, Lucerna A, Patel K. A brief literature review on heparin: to bolus or not to bolus, that is the question. Presented at: 26th Annual Research Day, Rowan-Virtua Research Day; May 5, 2022; Stratford, NJ. doi:10.31986/issn.2689-0690_rdw.stratford_research_day.1_2022
Literature Review

A search of the published medical literature revealed 6 studies investigating the researchable question:

What heparin infusion weight cap does literature support? Are there different weight caps based on indication? And is there literature to support heparin no sub-therapeutic bolus infusion protocols?

Level of evidence

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



Please see Tables 1-6 for your response.


 

Enter title in bold, with all first words capitalized, and without a reference number

Design

 Case report

Case presentation

A 32-year-old morbidly obese (weight 388 kg, body mass index [BMI] 134 kg/m2) male patient with obstructive sleep apnea, chronic obstructive pulmonary disease (COPD), venous stasis, hypoventilation, and chronic lower extremity cellulitis presented to the emergency department with complaints of intermittent cough and progressively worsening chest pain and shortness of breath for the past 9 days and was suspected to have pulmonary embolism. Initial unfractionated heparin therapy employed an empiric 5,000 unit bolus followed by an infusion rate capped at 1,500 units/hour per institutional protocol, corresponding to subtherapeutic anticoagulation levels. Incremental dose escalations over approximately 55 hours were required to reach therapeutic activated partial thromboplastin time (aPTT), culminating in a heparin infusion of 3,650 units/hour (~9.4 units/kg actual body weight [ABW]/hr). Despite achieving target anticoagulation, concerns about heparin-induced thrombocytopenia led to discontinuation and transition to fondaparinux. Upon reinitiation of heparin with a higher bolus (10,000 units) and infusion rate (3,000 to 3,550 units/hour), therapeutic aPTT was achieved after 48 hours; however, bleeding complications ensued. The patient ultimately developed fatal pulseless electrical activity. 

Study Author Conclusions

Despite limited data on heparin dosing in obesity, it was recommended to use an alternative dosing weight to determine initial heparin dosing when treating venous thromboembolism in morbidly obese patients. It is reasonable to consider one of the following formulas: dosing weight = ideal body weight (IBW) + 0.3(ABW–IBW), or dosing weight = IBW + 0.4(ABW– IBW).

The case underscored that conventional weight-based protocols with maximum dose restrictions can significantly delay attainment of therapeutic anticoagulation in morbidly obese patients. The report further synthesized retrospective analyses and smaller case series revealing that dosing strategies based on ABW often result in supratherapeutic anticoagulation and bleeding risk, while IBW may underestimate heparin requirements due to adipose tissue’s lower blood volume contribution.

Table 1 References:
[4] 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

Analysis of no bolus versus bolus unfractionated heparin nomograms in the management of pulmonary embolism: Insights from a real-world cohort
Design

Retrospective, single-center analysis of the Barnes-Jewish Hospital PE Response Team (PERT) database

N= 261

Objective To measure the association between no bolus vs bolus unfractionated heparin (UFH) nomograms and percent time with subtherapeutic activated thromboplastin time (aPTT) values within the first 24 hours of treatment for acute pulmonary embolism (PE)
Study Groups

No bolus (n= 63)

Bolus (n= 198)

Inclusion Criteria Patients with radiographically confirmed acute PE treated with intravenous UFH as initial therapy
Exclusion Criteria Not specified
Methods Retrospective analysis of patients treated with UFH for acute PE. Comparison of no bolus versus bolus UFH nomograms. Logistic regression used to identify factors associated with omission of the initial bolus.
Duration January 1, 2021, to July 1, 2025
Outcome Measures

Primary: Percent time with subtherapeutic aPTT value in the first 24 hours

Secondary: Time to achieve therapeutic aPTT, likelihood of achieving therapeutic aPTT within 24 hours

Baseline Characteristics  

No bolus

(n= 63)

Bolus

(n= 198)

Surgery within 12 weeks prior to PE diagnosis Associated with bolus omission (odds ratio [OR] 0.37)  
History of major bleed Associated with bolus omission (OR 0.14)  
Decrease in hemoglobin >1 g/dL Associated with bolus omission (OR 0.85)  
Results  

No bolus

(n= 63)

Bolus (n= 198) p-value
Median time in subtherapeutic range, hours (IQR) 15.3 (6.1-24.0) 8.1 (0.0-8.6) 0.01
Median time to achieve therapeutic aPTT, hours (IQR) 18.5 (7.0-24.0) 6.7 (5.8-12.7) 0.015
Percent time in subtherapeutic range 63% increase  - 0.001
Patients not achieving therapeutic aPTT at 24 hours 24 (38%) 21 (11%)  
Omission of an initial bolus was associated with a 58% decrease in likelihood of achieving a therapeutic or greater aPTT within 24 hours of UFH initiation (hazard ratio [HR] 0.42; 95% CI 0.30 to 0.59; p< 0.001).
Adverse Events Not specified
Study Author Conclusions Withholding the initial UFH bolus in the treatment of acute PE is associated with an increased percentage of time in subtherapeutic aPTT range within the first 24 hours of therapy. Evaluation of the risk of PE-related mortality and recurrent VTE after bolus omission is needed.
Critique The study provides valuable insights into the effects of withholding the initial UFH bolus in acute PE management. However, the retrospective design may introduce bias, and the study does not address long-term outcomes or adverse events. Further research is needed to evaluate the impact on PE-related mortality and recurrent VTE. Additionally, this study was available only as a published conference abstract; as such, the full results were not able to be independently verified.
Table 2 References:
[5] Xiong JQ, Von Nordheim D, Dei M, et al. Analysis of no bolus versus bolus unfractionated heparin nomograms in the management of pulmonary embolism: insights from a real-world cohort. Blood. 2025;146(Suppl 1):3117-3118. doi:10.1182/blood-2025-3117
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. The first aPTT was checked 6 hours following the infusion start. Further dose adjustments were made by registered nurses using protocol directions
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 24 hours; bleeding and thrombotic complications

Baseline Characteristics   Non-obese (n = 230) Obese (n = 146) Morbidly obese (n = 47)
Age, years 76.9 ± 12.7 72.3 ± 11.1 64.7 ± 11.5
Male 108 (47.0%) 89 (61.0%) 26 (55.3%)
White  226 (98.3%)  143 (97.9%)  46 (97.9%) 
BMI, kg/m2  24.5 ± 3.5  33.9 ± 2.6  46.8 ± 8.9
Charlson score 5.1 ± 2.7 5.0 ± 2.9 3.5 ± 2.5

Admission location 

          Floor

          ICU

 

172 (74.8%)

58 (25.2%)

 

104 (71.2%)

42 (28.8%)

 

26 (55.3%)

21 (44.7%)

Diagnosis

          DVT 

          PE 

 

94 (40.9%)

136 (59.1%)  

 

49 (33.6%)

97 (66.4%)  

 

15 (31.9%)

32 (68.1%) 

Heparin bolus  152 (66.1%)  87 (59.6%)  25 (53.2%)
Abbreviations: BMI, body mass index; DVT, deep vein thrombosis; ICU, intensive care unit; PE, pulmonary embolism.    
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 -
Cumulative incidence of therapeutic aPTT within 24 hours 70.7% 69.9% 61.7% -
Major bleeding events 15% 18.6% 16.4% -
Subtherapeutic aPTT within 24 hours 43.9% 39% 17% < 0.001
Supratherapeutic aPTT within 24 hours 42.2% 47.3% 61.7% 0.013
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
Critique The study's retrospective design and the smaller number of morbidly obese patients compared to other groups 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
Table 3 References:
[6] 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

Performance of Anti-Factor Xa Versus Activated Partial Thromboplastin Time for Heparin Monitoring Using Multiple Nomograms
Design

Prospective, single-center, nonrandomized study with historical control

N= 201

Objective To compare the performance of anti-factor Xa concentration versus activated partial thromboplastin time (aPTT) monitoring with multiple indication-specific unfractionated heparin (UFH)  nomograms
Study Groups

Anti-Xa monitoring (n= 101)

aPTT monitoring (n= 100)

Inclusion Criteria Patients who received intravenous UFH in the cardiology units (convenience sample)
Exclusion Criteria Use of IV UFH for less than 24 hours, treatment interruption for more than 10 hours, and 25% deviation from documented compliance with dose adjustment and/or monitoring with the heparin nomogram
Methods Patients in the prospective group had both anti-Xa and aPTT samples drawn, but anti-Xa was used for dosing adjustment. Nomograms for both anti-Xa and aPTT were designed for indication-specific uses (e.g., venous thromboembolism [VTE], acute coronary syndromes [ACS], atrial fibrillation/post-operative, and stroke/electrophysiology [EP]/ventricular assist device [VAD]/high-risk bleed)with different dose intensities and therapeutic anticoagulation targets. Only the stroke/EP/VAD/high-risk bleed nomogram did not include a bolus dose requirement. Dose adjustments and monitoring were based only on anti-Xa for the prospective cohort. 
Duration March 30, 2015, to June 30, 2015
Outcome Measures

Primary: Time to therapeutic anticoagulation

Secondary: Number of dose adjustments per 24 hours, discordance between anti-Xa and aPTT, length of stay (LOS), incidence of VTE, bleeding, mortality

Baseline Characteristics  

aPTT

(n= 100)

Anti-Xa

(n= 101)

p-value
Age, years 64.4 + 14.2 65.5 + 13.6 0.59
Race - White 89 (89) 94 (93.1) 0.43   
Race - Black 7 (7) 4 (4)
Race - Asian 0 (0) 1 (1)
Race - Unknown 4 (4) 2 (2)
Height, cm 171.8 + 11.3 170.5 + 10.1 0.40
Weight, kg 89.7 + 27.1 87.3 + 21.3 0.49
Body mass index (BMI), kg/m2 30.3 + 8.3 30.1 + 7.3 0.89
Kidney dysfunction 44 (44) 43 (42.6) 0.88
Concurrent medications - ASA 80 (80) 71 (70.3) 0.14
Concurrent medications - P2Y12 inhibitor 32 (32) 31 (30.7) 0.88
Concurrent medications - Glycoprotein IIb/IIIa inhibitor 1 (1) 1 (1) 1.00 
Concurrent medications - Warfarin 46 (46) 41 (40.6) 0.47
Concurrent medications - factor Xa inhibitor 0 (0) 1 (1) 1.00 
Concurrent medications - direct thrombin inhibitor DTI) 0 (0) 1 (1) 1.00 
Heparin nomogram - Afib/Post-Op 40 (40) 47 (46.5) 0.71    
Heparin nomogram - ACS 36 (36) 29 (28.7)
Heparin nomogram - VTE 22 (22) 23 (22.8)
Heparin nomogram - Stroke/EP/VAD/high-risk bleed 2 (2) 2 (2)
Bolus 39 (39) 47 (46.5) 0.31
Results  

aPTT

(n= 100)

Anti-Xa

(n= 101)

p-value
Time to therapeutic range (hours) 24 (2.5-118.8) 16 (0.8-69.3) < 0.01
Total time on heparin (hours) 66.5 (14.5-370) 61.5 (13-427) 0.84
Number of tests performed per 24 hours on heparin 2.7 (1.3-6.6) 2.7 (1-5.5) 0.81
Number of adjustments required 4 (0-24) 3 (0-16) 0.06
Number of adjustments required per 24 hours on heparin 1.5 (0-5.3) 1.2 (0-3.7) 0.01
LOS (days) 6.5 (1.6-37.9) 7.5 (1-43) 0.46
VTE 1 (1) 1 (1) 1.00
Bleeding 4 (4) 12 (11.9) 0.07
Mortality 4 (4) 0 (0) 0.06
Overall discordance rate between aPTT and anti-Xa was 49%>
Adverse Events No significant differences in clinical outcomes including bleeding and other adverse events were observed. Bleeding was evaluated based on the Thrombolysis in Myocardial Infarction noncoronary artery bypass grafting definition.
Study Author Conclusions Anti-Xa monitoring improved the time to therapeutic anticoagulation and led to fewer dose adjustments compared to the aPTT with multiple indication-based heparin nomograms.
Critique The study's prospective design with historical control provides a robust comparison, but the single-center nature and retrospective control arm may limit generalizability. The study did not perform a power calculation for clinical outcomes, which could affect the interpretation of the results. Additionally, the increased number of reported bleeds in the prospective group may indicate a need for further investigation into bleeding risks associated with anti-Xa monitoring.
Table 4 References:
[7] Whitman-Purves E, Coons JC, Miller T, et al. Performance of Anti-Factor Xa Versus Activated Partial Thromboplastin Time for Heparin Monitoring Using Multiple Nomograms. Clin Appl Thromb Hemost. 2018;24(2):310-316.
Impact of as Needed Heparin Boluses on Supratherapeutic Activated Partial Thromboplastin Time in Patients Managed With Extracorporeal Membrane Oxygenation
Design

Retrospective observational analysis

N= 32

Objective To compare the safety and efficacy of heparin nomograms with as needed boluses versus new nomograms without boluses in patients managed with ECMO
Study Groups Bolus nomogram (n= 23) No-bolus nomogram (n= 9)
Inclusion Criteria Adult patients cannulated on ECMO and initiated on an approved heparin bolus nomogram (January 1, 2018–December 31, 2019) or an approved heparin no-bolus nomogram (October 20, 2020–March 31, 2021)
Exclusion Criteria Managed on a custom UFH infusion outside of the approved nomograms, on UFH infusion for ≤24 hours, or if UFH was initiated before ECMO cannulation or at an outside hospital
Methods Data collection from EHR included past medical history, reason for ECMO support, baseline characteristics, UFH administration, bleeding, and thrombotic events. aPTT values were recorded at steady state, 6 hours after UFH initiation, and up to 72 hours. Safety events were collected according to ELSO Anticoagulation Guidelines.
Duration January 1, 2018–December 31, 2019 (bolus nomogram) October 20, 2020–March 31, 2021 (no-bolus nomogram)
Outcome Measures

Primary: Percentage of supratherapeutic aPTTs within the first 72 hours

Secondary: Percentage of aPTTs in therapeutic range or above within 24 hours, percentage of critically high PTTs, time to therapeutic aPTT, nomogram compliance

Baseline Characteristics   Bolus Nomogram (n = 23) No-bolus Nomogram (n = 9)
Age (years) 61 [43:65.5] 65 [61.5:67.5]
Weight (kg) 78 [68.8:90.5] 74 [59.7:91.5]
BMI 25 [23.6:29.4] 25.5 [24.4:33.2]
Gender: male 20 (87) 3 (33.3)
White race 19 (82.6) 4 (44.4)
Black race 3 (13)
Hispanic ethnicity 2 (22.2)
Other race/ethnicity 1 (4.3) 3 (33.3)
PTT (seconds) 30.9 [29.6:35.7] 30.3 [29.3:32.4]
Hemoglobin 12.2 [11.1:14.8] 12.1 [10.3:13.4]
Hematocrit 39.4 [33.9:46.5] 37.4 [32.9:42]
Platelets 248 [204.5:345] 263 [164.5:280]
INR 1.1 [1.1:1.2] 1.1 [1.1:1.2]
History of DVT/PE 2 (8.7) 1 (11.1)
History of bleeding on oral anticoagulant 0 0
Duration of ECMO (days) 16 [10:24] 43 [19:50]
Nomogram PTT goal - 50–70 1 (11.1)
Nomogram PTT goal - 60–80 22 (95.7) 8 (88.9)
Nomogram PTT goal - 80–100 1 (4.3)
Type of ECMO - Veno-venous 6 (26.1)
Type of ECMO - Veno-arterial 17 (73.9) 9 (100)
Starting heparin dose (units/kg/hr) 10 [7:15] 10 [9.5:12.5]
Duration of heparin (days) 11 [8:20] 16 [11.5:23.5]
Number of PTTs collected in first 72 hours per patient 11 [9.5:12] 9 [8:10.5]
Concomitant anticoagulant or antiplatelet 3 (13) 1 (11.1)
Results   Bolus Nomogram (n= 23) No-bolus Nomogram (n= 9) p-Value
Supratherapeutic aPTTs within 72 hours 11.5% 5.1% 0.101
Bleeding events 7 (30.4%) 1 (11.1%) 0.26
Thromboembolic events 0 0
Adverse Events Overall, there was 1 bleeding event in the no-bolus group (11.1%) and 7 in the bolus group (30.4%). There were no thromboembolic events in either group
Study Author Conclusions

The no-bolus UFH nomogram resulted in fewer supratherapeutic aPTTs and fewer bleeding events compared to the bolus nomogram, without compromising the ability to reach therapeutic aPTT values. This suggests that therapeutic anticoagulation can be achieved without boluses in ECMO patients, minimizing bleeding risks.

Critique

The study's strengths include its focus on a critical patient population and the comparison of two anticoagulation strategies. However, limitations include its retrospective design, small sample size, and single-center setting, which may limit the generalizability of the findings. Additionally, the study did not assess long-term outcomes or include ECMO circuit thrombotic events, which could provide a more comprehensive understanding of thrombotic risks.

 

Table 5 References:
[8] Corcoran DM, Kovacevic MP, Dell'Orfano H, Sylvester KW, Connors JM. Impact of as Needed Heparin Boluses on Supratherapeutic Activated Partial Thromboplastin Time in Patients Managed With Extracorporeal Membrane Oxygenation. Crit Pathw Cardiol. 2024;23(3):159-165. doi:10.1097/HPC.0000000000000347
The use of a bolus of intravenous heparin while initiating heparin therapy in anticoagulation following transient ischemic attack or stroke does not lead to increased morbidity or mortality
Design Subgroup analysis of a prospective, single-blinded, randomized clinical trial N= 206
Objective To evaluate the use of a heparin bolus via a subgroup analysis of a prospective, single-blinded, randomized clinical trial of a weight-based nomogram for heparin dosing in TIA and/or stroke
Study Groups

Bolus (n= 33)

No bolus (n= 173)

Inclusion Criteria Patients were 18 years of age or older; required anticoagulation for TIA(s) and/or stroke(s) due to suspected or known cardiac source, suspected hypercoagulable state, multiple vascular territory TIAs and/or stroke(s) of unknown etiology, and failure of antiplatelet therapy for prophylaxis of stroke
Exclusion Criteria Thrombolytic therapy in the past 24 h; current active hemorrhage; previous history of intracranial hemorrhage; stroke with suspected propensity to transform into hemorrhage; history of heparin-related complication(s) and/or allergy; inability to obtain informed consent; pregnancy or breast-feeding
Methods

Patients were randomized to either nomogram-directed anticoagulation or physician manually ordered anticoagulation. Intravenous boluses were provided if indicated by the enrolling physician. The bolus size was suggested to be 50 U/kg to a maximum of 5000 U. The initial infusion rate of intravenous heparin was determined by the nomogram or physician manual orders, and an aPTT was obtained 6 h following initiation of therapy.

Duration June 1999 to July 2001
Outcome Measures Primary: Time required for the first aPTT > 60 s, time required to achieve therapeutic aPTT range (60–90 s), percentage of time in therapeutic range
Baseline Characteristics   Bolus (n= 33) No bolus (n= 173)  
Patients 33 (16%) 173 (84%)  
Nomogram-maintained anticoagulation 18 (55%) 83 (48%)  
Physician-maintained anticoagulation 15 (45%) 90 (52%)  
Age (years) 62.1 ± 18.5 64.3 ± 12.7  
Sex (male) 18 (55%) 100 (58%)  
Results   Bolus (n= 33) No bolus (n= 173) P value
First aPTT (s) 87.6 ± 36.3 61.0 ± 18.1 < 0.001
Time to aPTT > 60 (h) 9.6 ± 7.3 14.5 ± 10.8 < 0.01
Time to aPTT = 60–90 (h) 13.9 ± 8.3 16.0 ± 11.9 0.33
Percentage of time in therapeutic range 68 ± 24% 71 ± 28% 0.34
Adverse Events There were no significant differences in the occurrence of major or minor complications between subgroups. No patients in either subgroup had documented complications of heparin-induced thrombocytopenia, skin necrosis, alopecia, hypoaldosteronism, or liver enzyme elevation
Study Author Conclusions

The use of a heparin bolus of 5000 U or less in the setting of TIA or stroke does not lead to a greater risk of complications, nor a greater number of unfavorable anticoagulation profiles in the anticoagulation management of TIA or stroke.

Critique

The study provides valuable insights into the use of heparin bolus in TIA or stroke, showing no increased risk of complications. However, the retrospective power analysis suggests a potential type II error due to the sample size. The study's subgroup analysis approach may limit the generalizability of the findings, and further randomized studies are needed to confirm these results.

 

Table 6 References:
[9] Toth C. The use of a bolus of intravenous heparin while initiating heparin therapy in anticoagulation following transient ischemic attack or stroke does not lead to increased morbidity or mortality. Blood Coagul Fibrinolysis. 2003;14(5):463-468. doi:10.1097/00001721-200307000-00006