Human platelet 5-hydroxyindoleacetic acid concentrations are meager and unlikely to be physiologically active or play a role in inflammation

Hematology. 2026 Dec 31;31(1):2733376. doi: 10.1080/16078454.2026.2733376. Epub 2026 Sep 18.

ABSTRACT

OBJECTIVES: A crucial role for platelet 5-hydroxyindoleacetic acid (5-HIAA, the principal serotonin metabolite) in human immune response and inflammation has been claimed. We have attempted to assess the likelihood of such a role for platelet 5-HAA. To assess the concentration of 5-HIAA in human platelets, we have reviewed prior reports of platelet 5-HIAA concentrations and to measure 5-HIAA concentrations in human platelet-poor plasma (PPP) and platelet-rich plasma (PRP) samples.

METHODS: A liquid chromatographic-mass spectrometric method (LC-MS) was used to measure 5-HIAA levels in simultaneously obtained PPP and PRP samples (n = 68).

RESULTS: Measured median PPP and PRP 5-HIAA concentrations of 9.7 ng/mL (IQR: 7.69-10.6), and 8.42 ng/mL (IQR: 6.57-10.3), respectively, were similar. Levels of PPP and PRP 5-HIAA were highly correlated (Spearman’s R² = .872. Measured levels were consistent with most prior reports.

DISCUSSION: Based on the observed PRP and PPP 5-HIAA concentrations, platelet 5-HIAA concentrations appear to be less than 1 ng/billion platelets. This compares to a typical mean concentration of human platelet serotonin of 600 ng/billion platelets.

CONCLUSION: It appears that the platelet has only negligible amounts of 5-HIAA and that platelet 5-HIAA is unlikely to play a role in human immune response, in inflammation, or in any other aspect of human physiology.

PMID:42758861 | DOI:10.1080/16078454.2026.2733376