Adjusted versus actual body weight dosing of 4-factor prothrombin complex concentrate in obese patients with warfarin-associated major bleeding

  • Keaton S. Smetana
  • Rachel Ziemba
  • Casey C. May
  • Michael J. Erdman
  • Edward T. Van Matre
  • G. Morgan Jones


The package insert of 4-factor prothrombin complex concentrate (4F-PCC) contains specific dosing recommendations stating to determine the patients dose based on their INR and weight, capping the weight at 100 kg. However, the mean body mass index (BMI) in the 4F-PCC U.S. approval study was 27 kg/m2, and there is a lack of literature identifying the ideal dosing strategy in obesity. We conducted a retrospective analysis of obese patients (BMI ≥ 30 kg/m2) who received 4F-PCC for warfarin associated emergent bleeding reversal. Treatment groups were those that received 4F-PCC on adjusted body weight (AdjBW) and those on actual body weight (ActBW). The primary outcome was the percent of patients achieving coagulopathy reversal, defined as a post-treatment INR < 1.4 for neurologic indications and < 1.5 for all others. A total of 78 obese patients were included (28 AdjBW and 50 ActBW). Baseline INR (3.1 vs. 2.8; p = 0.052) and BMI (33.6 vs. 33.6 kg/m2) were similar between groups. Achievement of goal INR was significantly lower in the AdjBW group (36% vs. 68%; p = 0.006). A majority of patients had intracranial hemorrhage (32% vs. 54%; p = 0.06), and the median dose of 4F-PCC was lower in the AdjBW group (2120 vs. 2500 units; p = 0.02). Dosing 4F-PCC using adjusted body weight in obese patients resulted in a significantly lower rate of coagulopathy reversal. ActBW should be used to dose 4F-PCC in obese patients when the 100 kg dose cap is utilized per the package insert recommendations.


Anticoagulation therapy Hematology Hemorrhagic disorders Prothrombin Obesity 


Author contributions

Study conception and design: KSS, RZ, CCM, MJE, ETVM, GMJ. Acquisition of data: KSS, RZ, CCM, MJE, GMJ. Analysis and interpretation of data: KSS, RZ, CCM, MJE, ETVM, GMJ. Critical revision of manuscript: KSS, RZ, CCM, MJE, ETVM, GMJ.

Compliance with ethical standards

Conflict of interest

All authors of this study have no direct or indirect conflicts of interest to disclose.

Supplementary material

11239_2018_1771_MOESM1_ESM.xlsx (31 kb)
Supplementary material 1 (XLSX 30 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Keaton S. Smetana
    • 1
  • Rachel Ziemba
    • 2
  • Casey C. May
    • 1
  • Michael J. Erdman
    • 3
  • Edward T. Van Matre
    • 4
  • G. Morgan Jones
    • 4
    • 5
    • 6
  1. 1.Department of PharmacyThe Ohio State University Wexner Medical CenterColumbusUSA
  2. 2.The Ohio State University College of PharmacyColumbusUSA
  3. 3.Department of PharmacyUniversity of Florida HealthJacksonvilleUSA
  4. 4.Department of Clinical Pharmacy and Translational Science, College of PharmacyUniversity of Tennessee Health Sciences CenterMemphisUSA
  5. 5.Department of PharmacyMethodist University HospitalMemphisUSA
  6. 6.Departments of Neurology and NeurosurgeryUTHSCMemphisUSA

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