Abstract Number: PB1480
Meeting: ISTH 2020 Congress
Background: Sudden infant death syndrome (SIDS) is the leading cause of postneonatal infant mortality. Subsets of SIDS infants show elevated serum serotonin (5-hydroxytryptamine [5-HT]) and abnormalities in 5-HT and 14-3-3 pathways in regions of the brainstem that mediate protective responses to life-threatening challenges during sleep. Platelets, which carry >98% of 5-HT in blood, share with neurons many of the same 5-HT and 14-3-3 pathways.
Aims: To determine if platelet 5-HT pathway and/or 14-3-3 pathway biomarkers are associated with SIDS.
Methods: Blood of infants dying suddenly and unexpectedly was collected under the auspices of California law and analyzed by whole blood flow cytometry to measure serotonin pathway markers (e.g. intra-platelet 5-HT, 5HT2a serotonin receptor) and 14-3-3 biomarkers (e.g. 14-3-3 zeta, 14-3-3-linked platelet surface glycoprotein [GP] Ibα and GPIX). Serum was analyzed for 5-HT and related molecules. Case and control adjudications were based upon autopsy reports, clinical information, and death scene investigations and were performed blinded to laboratory results.
Results: Serum 5-HT was significantly elevated in SIDS vs. controls (p=0.012, Figure, Table), replicating our previous findings (Haynes et al. PNAS 2017;114:7695). Intra-platelet (dense granule) 5-HT mean fluorescence intensity (MFI) was significantly higher in SIDS vs. controls (Figure). Platelet surface GPIX, which is linked to 14-3-3 via GPIbα, was lower in SIDS than in controls (p< 0.001) and 14-3-3 zeta itself was also lower in SIDS than in controls (p = 0.010) (Figure). GPIbα, which is susceptible to proteolysis, was not different between SIDS and controls. Other platelet end points were not significantly different between SIDS and controls.
Conclusions: The presence of both platelet and brain 5-HT and 14-3-3 abnormalities in SIDS suggests a global dysregulation of these pathways. Serum and platelet biomarkers may aid in the forensic determination of SIDS and have the potential to be predictive of risk for SIDS in living infants.
|Mean ± SD|
|Biomarker||SIDS||Control||SIDS log-transformed||Control log-transformed||P-val, 2 sample t-test of log-transformed|
|Serum 5-HT ng/mL||153.6 ± 97.0||77.8 ± 46.2||4.81 ± 0.71||4.21 ± 0.56||0.012|
|Adjusted Mean ± SE|
|Biomarker (adjusted for)||SIDS||Control||SIDS log-transformed||Control log-transformed||ANCOVA of log-transformed|
|Intra-platelet 5-HT MFI (PCA)||4.84 ± 0.39||3.66 ± 0.77||1.48 ± 0.08||1.13 ± 0.15||0.050|
|Platelet surface GPIX MFI (collection date)||242.4 ± 27.6||526.6 ± 52.8||5.21 ± 0.13||6.21 ± 0.24||<0.001|
|Platelet 14-3-3 MFI (PCA, collection date)||36.71 ± 5.75||64.08 ± 2.23||3.14 ± 0.14||4.05 ± 0.29||0.010|
[Platelet 5-HT and 14-3-3-related biomarkers in SIDS and controls. PCA, post-conceptional age.]
To cite this abstract in AMA style:Frelinger III AL, Haynes RL, Goldstein RD, Berny-Lang MA, Gerrits AJ, Riehs M, Haas EA, Paunovic B, Milne GL, Sleeper LA, Kinney HC, Michelson AD. Dysregulation of Platelet Serotonin and Platelet 14-3-3-Related Biomarkers in Sudden Infant Death Syndrome [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/dysregulation-of-platelet-serotonin-and-platelet-14-3-3-related-biomarkers-in-sudden-infant-death-syndrome/. Accessed December 6, 2021.
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