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Correspondence |

Average-Weight Methodology in Weight-Based Unfractionated Heparin Therapy in the Presence of Obesity FREE TO VIEW

Michael Safani, PharmD; Serge Tobias, MD; Michele Robinson, RN, NP; Joon Hwang, PharmD; Gregory S. Thomas, MD, MPH
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: None declared.

aMemorialCare Heart & Vascular Institute, Long Beach Memorial, Long Beach, CA

bDepartment of Pharmacy Services, Long Beach Memorial, Long Beach, CA

cSchool of Pharmacy, University of California, San Francisco, CA

dSchool of Medicine, University of California, Irvine, CA

eSkaggs School of Pharmacy, University of California, San Diego, CA

CORRESPONDENCE TO: Michael Safani, PharmD, Department of Pharmacy Services and MemorialCare Heart & Vascular Institute, Long Beach Memorial, 2801 Atlantic Ave, Long Beach, CA 90806


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2017;151(5):1187-1188. doi:10.1016/j.chest.2016.12.016
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Published online

We applaud the recent updates to the ninth edition of the American College of Chest Physicians on antithrombotic therapy. Their 2012 recommendation to use weight-based unfractionated heparin (UFH) was a remarkable advance in tailored heparin therapy. Because of the lack of definitive evidence, the ninth edition and the recent update are silent on how to address weight-based UFH in the presence of obesity. We published our limited experience with the use of average-weight methodology in patients with acute coronary syndrome previously. In this brief report, we add to that body of knowledge our experience with patients undergoing catheter ablation for atrial fibrillation (AF).

Optimal anticoagulation is critical in preventing thrombotic complications and reducing stroke or transient ischemic attack during catheter ablation for AF. The 2012 Heart Rhythm Society expert consensus statement recommends a periprocedural activated clotting time (ACT) of 300 to 400 s.

Following institutional review board approval, a single-center retrospective chart review was conducted in patients undergoing catheter ablation for AF to evaluate this prospectively initiated UFH dosing. A baseline CBC, activated partial thromboplastin time, and international normalized ratio were obtained prior to the procedure and one or more CBC were obtained the day after. Patients with an international normalized ratio > 1.5 within 24 hours of the procedure were excluded. We used the average-weight methodology to determine all weight-based UFH doses. Average weight is defined as the sum of actual and ideal weight divided by two. An IV loading dose of UFH 200 units/kg was followed by a maintenance infusion of 35 units/kg/h. Additional weight-based UFH boluses were administered to maintain an ACT of 300 to 400 s per Heart Rhythm Society recommendations. An ACT was measured within 10 to 15 min of the initial UFH loading dose, after each additional bolus dose, and every 15 to 30 min throughout the procedure. Sheath access sites were monitored for presence of hematoma twice daily until discharge. Hemorrhagic complications were assessed per Thrombosis in Myocardial Infarction (TIMI) criteria. i-STAT Celite ACT point-of-care analyzer and i-STAT ACT cartridges were used (Abbott Laboratories).

A total of 78 consecutive patients was studied. Seven patients were excluded due to dosing protocol violations. Mean age was 61 ± 9 years and 76% were men. BMI ranged from 22 to 41.5, with a mean of 30.5 ± 5.2, and 61 of the patients (86%) were overweight or obese. ACT outcomes were comparable independent of BMI subgroup (Table 1). There were no cases of TIMI minor or major bleeding from the time of the procedure to discharge. One patient experienced insignificant oozing from the femoral venous access site.

Table Graphic Jump Location
Table 1 ACT Outcomes as a Function of BMI Subgroups
a A P value of < .05 is considered significant using one-way analysis of variance to compare ACT values between three BMI groups.

ACT = activated clotting time; UFH = unfractionated heparin.

Raschke et al, showed that a weight-based heparin dose, compared with a fixed dose, is a powerful predictor of successful outcome in treatment of VTE. They used total weight in determining the weight-based heparin dose, and the number of obese patients was limited in their studies. Their post hoc analysis demonstrated an increased risk of bleeding in obese patients who received weight-based heparin, although none of the patients appeared to have undergone excessive anticoagulation, as reflected by the measured activated partial thromboplastin time, suggesting that bleeding may be partly related to heparin dose. Selection of proper dosing weight in weight-based UFH therapy is critical, as UFH has saturable pharmacokinetics, its dosing requirements are not directly proportional to body weight, it does not distribute into muscle or fat tissues, and it remains in the vascular circulation only. Anticoagulation in obese patients continues to be a therapeutic challenge resulting in both overtreatment and undertreatment., With increasing obesity in much of the world, use of average-weight methodology in weight-based UFH dosing represents an important opportunity to achieve the desired antithrombotic goal with efficiency and safety. This methodology was successful in achieving and maintaining the target ACT in the prevention of thrombotic events without hemorrhagic complications during catheter ablation for AF. Despite a wide range of BMI, ACT outcomes were consistent, reproducible, and independent of obesity. We have not studied patients with VTE and thus cannot comment on the efficacy of our approach in this setting.

References

Kearon C. .Aki E.A. .Ornelas J. .et al Antithrombotic therapy for VTE disease. CHEST Guideline and Expert Panel Report. Chest. 2016;149:315-352 [PubMed]journal. [CrossRef] [PubMed]
 
Safani M. .Hill S.E. .Winters R. .et al The use of average body weight in dosing unfractionated heparin. Chest. 2013;143:1840-1841 [PubMed]journal. [CrossRef] [PubMed]
 
Calkins H. .Kuck K.H. .Cappato R. .et al 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2012;9:632-696 [PubMed]journal. [CrossRef] [PubMed]
 
Serenbruany V.L. .Atar D. . Assessment of Bleeding events in clinical trials—proposal of a new classification. Am J Cardiol. 2007;99:288-290 [PubMed]journal. [CrossRef] [PubMed]
 
Raschke R.A. .Reilly B.M. .Guidry J.R. .et al The weight-based heparin dosing nomogram compared with a “standard care” nomogram. Ann Intern Med. 1993;119:874-881 [PubMed]journal. [CrossRef] [PubMed]
 
Raschke R.A. .Gollihare B. .Peirce J.C. .et al The effectiveness of implementing the weight-based heparin nomogram as a practice guideline. Arch Intern Med. 1996;156:1645-1649 [PubMed]journal. [CrossRef] [PubMed]
 
Estes J.W. . Clinical pharmacokinetics of heparin. Clin Pharmacokinet. 1980;5:204-220 [PubMed]journal. [CrossRef] [PubMed]
 
Barletta J.F. .DeYoung J.L. .McAllen K. .et al Limitations of standardized weight-based nomogram for heparin dosing in patients with morbid obesity. Surg Obes Relat Dis. 2008;4:748-753 [PubMed]journal. [CrossRef] [PubMed]
 
Hurewitz A.N. .Khan S.U. .Groth M.L. .et al Dosing of unfractionated heparin in obese patients with venous thromboembolism. J Gen Intern Med. 2011;26:487-491 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1 ACT Outcomes as a Function of BMI Subgroups
a A P value of < .05 is considered significant using one-way analysis of variance to compare ACT values between three BMI groups.

ACT = activated clotting time; UFH = unfractionated heparin.

References

Kearon C. .Aki E.A. .Ornelas J. .et al Antithrombotic therapy for VTE disease. CHEST Guideline and Expert Panel Report. Chest. 2016;149:315-352 [PubMed]journal. [CrossRef] [PubMed]
 
Safani M. .Hill S.E. .Winters R. .et al The use of average body weight in dosing unfractionated heparin. Chest. 2013;143:1840-1841 [PubMed]journal. [CrossRef] [PubMed]
 
Calkins H. .Kuck K.H. .Cappato R. .et al 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2012;9:632-696 [PubMed]journal. [CrossRef] [PubMed]
 
Serenbruany V.L. .Atar D. . Assessment of Bleeding events in clinical trials—proposal of a new classification. Am J Cardiol. 2007;99:288-290 [PubMed]journal. [CrossRef] [PubMed]
 
Raschke R.A. .Reilly B.M. .Guidry J.R. .et al The weight-based heparin dosing nomogram compared with a “standard care” nomogram. Ann Intern Med. 1993;119:874-881 [PubMed]journal. [CrossRef] [PubMed]
 
Raschke R.A. .Gollihare B. .Peirce J.C. .et al The effectiveness of implementing the weight-based heparin nomogram as a practice guideline. Arch Intern Med. 1996;156:1645-1649 [PubMed]journal. [CrossRef] [PubMed]
 
Estes J.W. . Clinical pharmacokinetics of heparin. Clin Pharmacokinet. 1980;5:204-220 [PubMed]journal. [CrossRef] [PubMed]
 
Barletta J.F. .DeYoung J.L. .McAllen K. .et al Limitations of standardized weight-based nomogram for heparin dosing in patients with morbid obesity. Surg Obes Relat Dis. 2008;4:748-753 [PubMed]journal. [CrossRef] [PubMed]
 
Hurewitz A.N. .Khan S.U. .Groth M.L. .et al Dosing of unfractionated heparin in obese patients with venous thromboembolism. J Gen Intern Med. 2011;26:487-491 [PubMed]journal. [CrossRef] [PubMed]
 
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