Case Report: Low Hematocrit Leading to Tacrolimus Toxicity

Area of Science:

• Pharmacology
• Transplantation Medicine
• Clinical Pharmacy

Background:

• Tacrolimus, a calcineurin inhibitor, has a narrow therapeutic index and significant pharmacokinetic variability.
• Therapeutic drug monitoring of tacrolimus in whole blood is standard practice.
• Tacrolimus binds extensively to erythrocytes, making whole-blood concentrations sensitive to hematocrit levels.

Observation:

• Low hematocrit can disproportionately increase unbound tacrolimus plasma concentrations.
• This can lead to toxicity even with seemingly therapeutic whole-blood trough concentrations.
• A case involving a teenage transplant patient with low hematocrit and ABCB1 polymorphism is presented.

Findings:

• Low hematocrit necessitated a significant tacrolimus dosage increase in the patient.
• The interplay of low hematocrit, increased tacrolimus dosage, and ABCB1 polymorphism contributed to nephrotoxicity.
• This case underscores the limitations of whole-blood monitoring in specific patient populations.

Implications:

• Hematocrit levels must be carefully considered when interpreting tacrolimus whole-blood trough concentrations.
• Monitoring unbound tacrolimus concentrations may be crucial in patients with fluctuating hematocrit.
• Personalized dosing strategies considering hematocrit and genetic factors are essential for optimizing tacrolimus therapy and preventing toxicity.