Abstract Number: LPB0034
Meeting: ISTH 2021 Congress
Background: Depression is a risk factor of cardiovascular disease (CVD) and linked to worsened CVD outcomes. Serotonin is a key neurotransmitter in depressive pathology, contained in platelet dense granules, and a weak activator of platelets.
Aims: Our study assessed the link between platelet reactivity traits, depression and antidepressant (AD)-use in a large population sample.
Methods: This study was conducted in the Framingham Heart Study (N= 3,140). AD-use (N=563) and aspirin-use (N=681) at the time of platelet assays was noted. Depression was measured using the Center for Epidemiological Studies-Depression (CES-D) survey. Platelet reactivity traits were measured across multiple agonists using light transmission aggregometry (LTA), Multiplate whole blood impedance aggregometry (MP), Total-Thrombus Formation Assay System (T-TAS), Optimul 96-well plate assay, and flow cytometry (FC). We utilized a linear mixed effects model to test associations between platelet reactivity traits and depression, adjusting for age, sex and aspirin-use. Similarly, we analyzed trait associations with any AD-use, serotonin-affecting ADs, and norepinephrine-affecting ADs, respectively.
Results: There were strong associations with reduced platelet function and AD-use, particularly with serotonin-affecting medications. This included decreased Optimul epinephrine (P<4.49E-14) and U46619 (P<8.56E-11) maximal aggregation, decreased LTA ADP final aggregation (P<1.26E-07), higher LTA ADP disaggregation (P<2.14E-07), and decreased ADP activation by FC, among others. Similar associations with increased CES-D symptomology (thresholds >16 or >21) were largely attenuated after adjusting for current AD-use. Observations were also significant within the aspirin strata.
Conclusions: In the largest study yet of AD-use on platelet function we show that antidepressants, particularly serotonin-affecting drugs, inhibit platelet reactivity. Serotonin potentiates platelet reactivity to weak agonists such as ADP and epinephrine. Thus, our results are consistent with AD-use leading to platelet serotonin depletions, decreased stability of platelet aggregates, and overall decreased aggregation to multiple agonists, which may be a mechanism by with ADs increase risk for adverse bleeding events.
To cite this abstract in AMA style:Grech J, Chan M, Lachapelle A, Thibord F, Schneider Z, Armstrong P, Wallace de Melendez C, Warner T, Chen M-, Johnson A. Effects of Depression and Antidepressant Use on Platelet Reactivity Traits [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/effects-of-depression-and-antidepressant-use-on-platelet-reactivity-traits/. Accessed December 11, 2023.
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