Sex differences of leukocyte-platelet interactions and on-treatment platelet reactivity in patients with atherosclerosis

Objective: To investigate differences of platelet activation and on-treatment residual platelet reactivity between female and male patients with atherosclerotic cardiovascular disease. Methods: We compared P-selectin expression, activated glycoprotein (GP) IIb/IIIa and leukocyte-platelet aggregates (LPA) by flow cytometry between 110 female and 206 male patients undergoing angioplasty and stenting. On-treatment residual platelet reactivity was determined by two test systems. Results: The expression of P-selectin and GPIIb/IIIa did not differ significantly between female and male patients. In contrast, females showed a significantly more pronounced formation of LPA in vivo, in response to thrombin receptor-activating peptide-6 and in response to adenosine diphosphate. Further, high LPA were seen more frequently in female patients. Finally, protease-activated receptor (PAR)-1 mediated platelet reactivity by both assays was significantly higher in females. Conclusion: Female sex is associated with a more pronounced formation of LPA and increased PAR-1 mediated platelet reactivity in atherosclerotic cardiovascular disease.