# A Case of Pulmonary Hemorrhage, Supratherapeutic International Normalized Ratio (INR), and Anti-neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis: Unmasking a Potential Link to Tirzepatide

## TL;DR

A patient taking tirzepatide and warfarin developed severe bleeding and autoimmune symptoms, suggesting a possible link between the drug and immune-related complications.

## Contribution

This case report suggests a potential pharmacokinetic interaction and autoimmune trigger associated with tirzepatide.

## Key findings

- The patient experienced supratherapeutic INR and pulmonary hemorrhage after increasing tirzepatide dose.
- Elevated c-ANCA levels and signs of vasculitis were observed, requiring immunosuppressive treatment.
- The case raises concerns about tirzepatide's effects on drug metabolism and immune regulation.

## Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as tirzepatide (Mounjaro), are widely used for type 2 diabetes and obesity, but their effects on drug metabolism and immune regulation remain areas of concern. We report a 64-year-old male with diabetes and chronic deep vein thrombosis (DVT) on warfarin who developed pulmonary hemorrhage, acute kidney injury (AKI), and markedly elevated cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) levels shortly after increasing his tirzepatide dose. His international normalized ratio (INR) was supratherapeutic at 8.7, prompting warfarin discontinuation. Despite INR normalization, he developed diffuse alveolar hemorrhage (DAH) and worsening renal function. Workup revealed ANCA-associated vasculitis, though confirmation by renal biopsy was pending at the time of the patient’s expiration. He required corticosteroids, plasmapheresis, rituximab, and hemodialysis. This case highlights potential pharmacokinetic interactions between tirzepatide and warfarin, as well as a possible role for tirzepatide in triggering autoimmunity. While definitive causality remains unclear, clinicians should closely monitor INR levels in patients on GLP-1RAs and warfarin and be vigilant for autoimmune complications in those presenting with pulmonary-renal syndromes. Further research is needed to explore the immunomodulatory effects of tirzepatide.