A case of renal-coloboma syndrome associated with mental developmental delay exhibiting a novel PAX2 gene mutation.

INTRODUCTION

Sacubitril/valsartan is the first approved angiotensin receptor-neprilysin inhibitor (ARNI) and a cornerstone therapy for heart failure with reduced ejection fraction (HFrEF). While its clinical benefits are well established, adverse drug reactions (ADRs) beyond the recognized profile of hypotension, hyperkalaemia, and renal impairment remain incompletely characterized.

CASE DESCRIPTION: We report a case of isolated elevation in prothrombin time (PT) and international normalized ratio (INR) in a 58-year-old male with HFrEF receiving sacubitril/valsartan 49/51 mg twice daily, without any concurrent anticoagulant therapy. Approximately 6 weeks after initiation, PT was 18.4 seconds and INR was 1.7. Temporary discontinuation (dechallenge) led to normalization within 2 weeks; cautious re-challenge resulted in recurrent INR elevation. Naranjo Adverse Drug Reaction Probability Scale criteria yielded a score of +9, consistent with a probable drug-induced adverse event.

CONCLUSION

This case highlights a potentially underrecognized coagulopathic ADR associated with sacubitril/valsartan, manifesting as elevated PT/INR without anticoagulant use. Clinicians should consider periodic coagulation monitoring in patients on ARNI therapy. Further pharmacovigilance studies and mechanistic investigations are strongly warranted.

LEARNING POINTS: Sacubitril/valsartan may cause isolated elevation of prothrombin time and international normalized ratio in the absence of anticoagulant therapy, liver disease, or vitamin K deficiency; a potentially underrecognized adverse drug reaction (ADR).The dechallenge-rechallenge pattern, together with a Naranjo score of +9, provides robust pharmacovigilance evidence implicating angiotensin receptor-neprilysin inhibitor therapy as the causative agent and supports baseline and periodic coagulation monitoring.Clinicians prescribing sacubitril/valsartan should be vigilant for this coagulopathic ADR, especially in patients at elevated bleeding risk, and should report cases to pharmacovigilance registries to facilitate systematic signal detection.