Changes in Platelet Level and Activation as Hematological Biomarkers of Antipsychotic-Induced Systemic Inflammatory Response: Narrative Review

Research over the last decade has shown that schizophrenia spectrum disorders (SSDs) cannot be viewed exclusively as a neurotransmitter pathology. A significant proportion of patients, especially those in the acute phase and with treatment resistance, exhibit signs of low-grade inflammation (LGI), which is associated with cardiovascular comorbidity, including the risk of venous thromboembolism (VTE). The role of antipsychotics (APs), which are the mainstay of SSDs therapy, in the development of VTE remains controversial. On one hand, preclinical in vitro and in vivo studies demonstrate an antiplatelet effect of APs. This effect is mediated through blockade of adenosine diphosphate (P2Y1 and P2Y2) and serotonin (5-HT2A) receptors, and inhibition of thromboxane A2. On the other hand, clinical in vivo studies indicate the persistence or even increase of procoagulant platelet activity and LGI, which significantly elevates the risk of VTE in patients with SSDs during long-term AP treatment. Materials and Methods: In this narrative review, we analyzed and summarized the results of preclinical and clinical studies on biomarkers of AP-induced platelet activation, as well as their prognostic role in assessing VTE risk in patients with SSDs. Results: As a result, the knowledge of psychiatrists regarding the potential negative impact on platelet hemostasis has been updated for firstand new-generation APs. It has been shown that asenapine and amisulpride carry the highest risk of developing AP-induced VTE. Haloperidol and droperidol have a dose-dependent risk of VTE. An increased risk of AP-induced pathological bleeding is observed with the use of quetiapine, thioridazine, thiothixene, and flupentixol. Conclusion: The diverse effects of APs on platelet hemostasis have been demonstrated. This underscores the need for a differentiated approach to selecting APs and the complexity of predicting the additive effect during AP polytherapy. Dynamic monitoring of hematological biomarkers (platelet and inflammatory) is important for reducing the risk of developing VTE in patients with SSDs.