Increased basal platelet activity, plasma adiponectin levels, and diabetes mellitus are associated with poor platelet responsiveness to in vitro effect of aspirin

• Published in: Thrombosis research 2007-01, Vol.119 (4), p.517-524
• Main Authors: Takahashi, Shinichi, Ushida, Miho, Komine, Risa, Shimizu, Aya, Uchida, Toshihiro, Ishihara, Hiroaki, Shibano, Toshiro, Watanabe, Gentaro, Ikeda, Yasuo, Murata, Mitsuru
• Format: Article
• Language: English
• Subjects: Adiponectin; Adiponectin - blood; Adult; Aspirin - administration & dosage; Aspirin resistance; Associated diseases and complications; Biological and medical sciences; Blood and lymphatic vessels; Blood coagulation. Blood cells; Blood Platelets - drug effects; Cardiology. Vascular system; Diabetes mellitus; Diabetes Mellitus - blood; Diabetes. Impaired glucose tolerance; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug Resistance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Fundamental and applied biological sciences. Psychology; Hematology, Oncology and Palliative Medicine; Humans; Hyperplatelet activity; In Vitro Techniques; Male; Medical sciences; Middle Aged; Molecular and cellular biology; PFA-100; Platelet; Platelet Aggregation Inhibitors - administration & dosage; Platelet Function Tests - methods
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2006.04.004

Abstract Introduction Aspirin is one of the most effective antiplatelet agents and is now commonly used to prevent vascular events. In some patients, however, recurrent vascular events have been demonstrated despite aspirin therapy. Our objective was to characterize individuals showing poor response to in vitro effect of aspirin, using PFA-100. Methods One hundred sixty-eight healthy male subjects were analyzed. We assessed platelet function tests, including PFA-100, whole blood aggregation, and optical platelet aggregation. Also measured were hemostatic and other parameters including von Willebrand factor (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), soluble vascular adhesion molecule-1 (sVCAM-1), high sensitive C-reactive protein (hs-CRP), and adiponectin. Poor responders were defined as having a collagen/epinephrine-induced closure time (CEPI-CT) under 250 s with PFA-100 when incubated with 10 μM aspirin, whereas good responders were defined as having a CEPI-CT of more than 250 s. Results and conclusions PFA-100 tests revealed that 40 subjects (24%) were poor responders (PR) and 128 (76%) were good responders (GR). Poor responsiveness was significantly associated with (1) higher basal platelet activities in PFA-100, as well as in whole blood aggregation and aggregometer;(2) increased level of adiponectin (8.8 ± 4.1 μg/mL [PR] vs 7.3 ± 2.9 μg/mL [GR], p = 0.010);and (3) the presence of diabetes mellitus (17.5% [PR] vs 4.7% [GR], p = 0.009). Importantly, whereas 24% of the subjects showed insufficient inhibition in PFA-100 when incubated with 10 μM aspirin, almost all subjects showed maximum inhibition with 30 μM aspirin. These observations suggest that higher doses of aspirin might overcome aspirin resistance.