Open Access

Sebastien Elvinger, Stephanie G. Kuehne, Andrea Patrignani, Maximilian Tscharre, Matthias Freynhofer, Leor Perl, Ran Kornowski, Francesca Cesari, Rossella Marcucci, Laura Novelli, Isabell Bernlochner, Philip W. Raake, Mauro Chiarito, Dario Bongiovanni

• Background: Platelets play a crucial role in immune responses and haemostasis. Among them, reticulated platelets (RPs) have gathered attention for their association with prothrombotic states and as a potential biomarker for cardiovascular events. However, the sex-specific prognostic value of RPs remains underexplored. Objective: This study aimed to systematically review and analyse sex-specific differences in the prognostic role of RPs in cardiovascular disease. Methods: We conducted a comprehensive search on studies that reported patient outcomes related to RPs. Study authors were contacted to provide sex-specific patient-level data. Two studies were excluded due to data unavailability. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints included cardiovascular death, myocardial infarction, stroke, urgent revascularization, and bleeding incidents. All outcomes were stratified by sex. Results: The analysis included 5 studies,Background: Platelets play a crucial role in immune responses and haemostasis. Among them, reticulated platelets (RPs) have gathered attention for their association with prothrombotic states and as a potential biomarker for cardiovascular events. However, the sex-specific prognostic value of RPs remains underexplored. Objective: This study aimed to systematically review and analyse sex-specific differences in the prognostic role of RPs in cardiovascular disease. Methods: We conducted a comprehensive search on studies that reported patient outcomes related to RPs. Study authors were contacted to provide sex-specific patient-level data. Two studies were excluded due to data unavailability. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints included cardiovascular death, myocardial infarction, stroke, urgent revascularization, and bleeding incidents. All outcomes were stratified by sex. Results: The analysis included 5 studies, reporting outcomes in 1835 patients (527 females and 1308 males). RPs are a significant predictor of MACCE independently of sex males (OR 1.99 [95% CI 1.3, 3.05; I2 = 29%]), females (2.29 [95% CI 1.31, 3.99; I2 = 10%]). For cardiovascular death RPs were predictive in females (OR 3.29 [95% CI 1.69, 6.40] I2 = .83%) and showed a trend toward significance in males (OR 2.19 95% CI [.98, 4.9] I2 = 42.72%). No sex-specific differences were observed in all other secondary endpoints. Conclusion: RPs significantly predict MACCE in cardiovascular disease independently from sex and may have a stronger association with cardiovascular death in females. Further research is needed to explore the sex-specific mechanisms of RPs' prognostic value.…