2. Academic Validation
  3. Sex-specific platelet activation through protease-activated receptor-1 in patients undergoing cardiac catheterization

Sex-specific platelet activation through protease-activated receptor-1 in patients undergoing cardiac catheterization

  • Atherosclerosis. 2021 Dec;339:12-19. doi: 10.1016/j.atherosclerosis.2021.11.011.
Thomas Gremmel 1,  Alan D Michelson 2,  Patricia P Wadowski 3,  Joseph Pultar 3,  Constantin Weikert 3,  Maximilian Tscharre 3,  Silvia Lee 3,  Simon Panzer 4,  Andrew L Frelinger 3rd 2
Affiliations

Affiliations

  • 1 Center for Platelet Research Studies, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, USA; Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria; Institute of Antithrombotic Therapy in Cardiovascular Disease, Karl Landsteiner Society, St. Poelten, Austria; Department of Internal Medicine I, Cardiology and Intensive Care Medicine, Landesklinikum Mistelbach-Gänserndorf, Mistelbach, Austria. Electronic address: [email protected].
  • 2 Center for Platelet Research Studies, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, USA.
  • 3 Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
  • 4 Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.
PMID: 34808540 DOI: 10.1016/j.atherosclerosis.2021.11.011
Abstract

Background and aims: Protease-activated Receptor (PAR)-1-mediated platelet activation may vary according to sex and clinical situation. In order to investigate sex-specific platelet activation through PAR-1, we assessed platelet response to Thrombin receptor-activating peptide (TRAP) in 562 patients undergoing cardiac catheterization without (Group 1A) and with (Group 1B) acute coronary syndrome (ACS). Subsequently, we sought to confirm our findings in 287 patients undergoing elective (Group 2A) or acute (Group 2B) percutaneous coronary intervention.

Methods: TRAP-stimulated platelet surface expression of P-Selectin and activated glycoprotein IIb/IIIa (GPIIb/IIIa) were measured by flow cytometry in Group 1. LIGHT transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) in response to TRAP were assessed in Group 2.

Results: In Group 1A, platelet activation in response to TRAP was significantly higher in women compared to men (P-selectin: 511 MFI [443-597 MFI] vs. 471 MFI [393-552 MFI]; GPIIb/IIIa: 84 MFI [58-119 MFI] vs. 70 MFI [47-103 MFI]; both p ≤ 0.002). In contrast, in Group 1B, TRAP-stimulated P-Selectin and activated GPIIb/IIIa were similar in men and women (both p ≥ 0.3). Likewise, TRAP-stimulated platelet aggregation was significantly higher in female patients in Group 2A (LTA: 66% [54-76%] vs. 51% [41-65%]; MEA: 78 AU [66-107 AU] vs. 62 AU [52-88 AU]; both p ≤ 0.02), whereas men and women in Group 2 B had similar platelet aggregation (p = 0.5). The occurrence of ischemic endpoints did not differ significantly between men and women in Group 1A and Group 1B.

Conclusions: Platelet PAR-1 signaling is more pronounced in women than in men without ACS. In ACS, however, PAR-1-mediated platelet activation is similar in male and female patients.

Keywords

Acute coronary syndrome; Cardiac catheterization; Platelet activation; Protease-activated receptor-1; Sex.

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