Neutrophils are the most abundant of the circulating immune cells and are the first to be recruited to sites of inflammation. Neutrophils are a heterogeneous group of immune cells from which are derived extracellular traps (NETs), reactive oxygen species, cytokines, chemokines, immunomodulatory factors, and alarmins that regulate the recruitment and phenotypes of neutrophils, macrophages, dendritic cells, T cells, and B cells. In addition, cytokine-stimulated neutrophils can express class II major histocompatibility complex and the internal machinery necessary for successful antigen presentation to memory CD4⁺ T cells. This may be relevant in the context of vaccine memory. Neutrophils thus emerge as orchestrators of immune responses that play a key role in determining the outcome of infections, vaccine efficacy, and chronic diseases like autoimmunity and cancer. This review aims to provide a synthesis of current evidence as regards the role of these functions of neutrophils in homeostasis and disease.

Background: Heparin-induced thrombocytopenia (HIT) is a rapid, life-threatening adverse drug reaction, with the widely used 4T score being the critical clinical tool guiding the need for serological confirmation. This study aimed to validate the diagnostic utility of the 4T score and evaluate its application in a tertiary hospital in Saudi Arabia. Methods: In this retrospective cohort study, we analyzed 449 patients with suspected HIT, comparing their initially recorded clinical 4T scores with those recalculated by trained specialists, using the anti-PF4/heparin IgG ELISA as the reference standard for HIT confirmation. Results: Of the 292 patients who underwent laboratory testing, the HIT positivity rate was 6.5% (n = 19). The primary finding was a markedly low agreement (15.4%) between the system-recorded and the standardized physician-calculated 4T scores, indicating significant inter-observer variability. Despite this, higher calculated 4T scores remained significantly associated with positive HIT test results, and the anti-PF4/heparin IgG ELISA demonstrated 100% sensitivity and 100% negative predictive value (NPV). Conclusions: While the 4T score is indispensable for guiding the diagnostic pathway, the observed profound inter-observer variability highlights an urgent need for standardized scoring training and protocol refinement to enhance diagnostic accuracy and reduce inappropriate therapeutic interventions.