Influence of Kidney Transplant Status on Warfarin Dose, Anticoagulation Control, and Risk of Hemorrhage

Pharmacotherapy. 2017 Nov;37(11):1366-1373. doi: 10.1002/phar.2032. Epub 2017 Nov 2.

Abstract

Study design: To assess whether warfarin dose requirement, anticoagulation control, and risk of hemorrhage differ in kidney transplant recipients (KTRs) compared with patients without kidney transplants (non-KTRs).

Design: Analysis of data from the Warfarin Pharmacogenetics Cohort, a prospective cohort of first-time warfarin users followed at two anticoagulation clinics.

Setting: Two outpatient anticoagulation clinics at two large, academic, tertiary care hospitals.

Patients: Adults aged 20 years or older starting warfarin for anticoagulation with a therapeutic international normalized ratio (INR) goal of 2-3 who were KTRs (n=65) or non-KTRs (n=1630).

Measurements and main results: Warfarin dose requirement, anticoagulation control, and risk of hemorrhage were assessed in each group. KTRs required an approximately 20% lower warfarin dose (4.7 vs 5.6 mg/day, p=0.0005) compared with non-KTRs. Genetic variants had similar effects on dose in both groups. Mean percentage of time in therapeutic range (PTTR) was similar among KTRs and non-KTRs. Although the proportion of patients achieving good anticoagulation control (PTTR ≥ 60%) was low in both groups, it was similar among KTRs and non-KTRs. KTRs had a higher risk of major hemorrhage (hazard ratio 2.1, p=0.0081), but this difference was not statistically significant after controlling for kidney function, clinical, and genetic factors.

Conclusion: KTRs initiating warfarin require lower doses and closer monitoring to optimize anticoagulation therapy. Additional studies are needed to confirm these findings.

Keywords: anticoagulation; hemorrhage; kidney transplant; warfarin.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Drug Monitoring / methods
  • Female
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Humans
  • International Normalized Ratio
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Outpatient Clinics, Hospital
  • Pharmacogenetics
  • Prospective Studies
  • Risk
  • Warfarin / administration & dosage*
  • Warfarin / adverse effects

Substances

  • Anticoagulants
  • Warfarin