Update (June 9, 2026): Rapamycin Impairs Platelet Aggregation and Procoagulant Phenotypes in Cats Ex Vivo

TL;DR. An April 2026 ex vivo study found low-dose delayed-release rapamycin impairs platelet aggregation and procoagulant platelet formation in domestic cats, raising new monitoring considerations for clinicians using sirolimus in feline HCM patients.

What just dropped

Shaverdian M, Nguyen N, Fitzgerald S, Grubb L, Stern JA, and Li RHL published "Ex vivo effects of low dose delayed release rapamycin on agonist-induced platelet aggregation, activation and procoagulant platelet phenotypes in domestic cats" in Scientific Reports (April 2026; PMID 41965408; PMC13221459; DOI 10.1038/s41598-026-46991-z). The study was conducted at UC Davis School of Veterinary Medicine and NC State College of Veterinary Medicine, groups with active feline HCM rapamycin programs. This is the first dedicated feline platelet study for rapamycin at the dose range being investigated for HCM.

Context

Sirolimus (rapamycin), an mTOR inhibitor, has been under investigation for feline hypertrophic cardiomyopathy on the basis that mTOR pathway dysregulation contributes to myocardial hypertrophy in cats. The RAPACAT trial and related pilot studies demonstrated structural and functional effects of low-dose rapamycin in HCM cats. Cats with HCM are at risk for arterial thromboembolism (ATE), one of the most feared sequelae of the disease, mediated in part by activated platelets and procoagulant platelet phenotypes (phosphatidylserine-exposing platelets that amplify thrombin generation).

The new study investigated whether rapamycin itself, at doses used in feline HCM investigation, alters platelet function - a safety-relevant question distinct from the efficacy evidence base.

What this changes in sirolimus-feline-hypertrophic-cardiomyopathy (https://www.thevoyage.ai/forvets/knowledge/sirolimus-feline-hypertrophic-cardiomyopathy)

The RAPACAT evergreen page summarizes the HCM efficacy evidence for sirolimus and notes that long-term safety data in cats are still accruing. Shaverdian et al. 2026 adds important nuance to that safety section:

• The study found that low-dose delayed-release rapamycin reduced agonist-induced platelet aggregation ex vivo in cats
• Procoagulant platelet phenotypes (phosphatidylserine-exposing, high mitochondrial membrane potential loss) were also reduced
• The study's keywords include cardiogenic arterial thromboembolism, indicating the authors explicitly frame this in the HCM-ATE context

Clinical implication: Reduced procoagulant platelet activity could theoretically be beneficial in HCM cats at risk for ATE, or could impair hemostasis in cats with concurrent bleeding risk. This is a hypothesis-generating ex vivo study only; platelet function was assessed in blood incubated with rapamycin, not in vivo. No clinical bleeding events or thrombotic events in cats are reported. Clinicians using sirolimus in HCM patients should be aware of this potential pharmacodynamic interaction and may consider baseline platelet function assessment if concurrent hemostatic risk is present.

References

1. Shaverdian M, Nguyen N, Fitzgerald S, et al. Ex vivo effects of low dose delayed release rapamycin on agonist-induced platelet aggregation, activation and procoagulant platelet phenotypes in domestic cats. Sci Rep. 2026;16(1):16696. https://pubmed.ncbi.nlm.nih.gov/41965408/

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Changelog

• 2026-06-09: First published.

Related reads

• Rapamycin (Sirolimus) for Feline Hypertrophic Cardiomyopathy: RAPACAT Trial and Evidence