The amino acid content in the daily diet of seniors negatively correlates with the degree of platelet aggregation in a sex- and agonist-specific manner.

Aging is a significant risk factor for the development of thrombotic diseases, dependent on blood platelet reactivity. However, the risk of thrombosis also appears to be significantly modulated by dietary nutrient content. The aim of the current study was to assess the relationship between the amount of amino acids present in the daily diet (not supplemented) and the reactivity of blood platelets to arachidonate, collagen and ADP in 246 women and men aged 60-65 years. Platelet reactivity was tested using whole blood impedance aggregometry. Amino acid intake was assessed with a 24-hour Recall Questionnaire and calculated with Dieta 5.0 software. Older subjects receiving higher amounts of all essential amino acids with their daily diet exhibit significantly lower platelet responsiveness to AA-, COL- and ADP in a sex-specific manner: dietary amino acid content was more closely associated with AA- and, to some extent, ADP-induced platelet reactivity in women, and with COL-induced platelet aggregability in men. Therefore, dietary amino acid content may be a novel factor responsible for attenuating platelet reactivity in a sex- and agonist-specific manner.

Does high on-treatment platelet aggregability reflect poor individual response to clopidogrel?

INTRODUCTION: On-treatment platelet aggregability represents the major form of functional assessment for patients treated with P2Y12 receptor antagonists, with "high" on-treatment platelet aggregability (HTPA) predicting thrombotic risk. However HTPA reflects a variable combination of pre-treatment hyperaggregability and poor response to P2Y12 antagonists. We have previously shown that integrity of platelet adenylate cyclase/cAMP signaling, assessed with PGE1, is a strong predictor of individual responses to clopidogrel. We therefore sought to determine the extent to which HTPA reflects impaired platelet responsiveness to clopidogrel. METHODS: Using data from our previous investigations of acute and sub-acute effects of clopidogrel, we analyzed the relationship between on-treatment aggregability and acute/steady state responsiveness to clopidogrel, utilizing ADP, the thromboxane A2 mimetic U46619, and thrombin receptor-activating peptide (TRAP) as pro-aggregants. The relationship between anti-aggregatory response to PGE1 and both on-treatment and pre-treatment aggregability was also examined. RESULTS AND CONCLUSIONS: With all 3 pro-aggregants, (1) response to clopidogrel after 4 h, as measured by ΔADP response, exhibits a strong inverse relationship with on-treatment aggregation, with a similarly inverse relationship between pre-treatment PGE1 response and on-treatment aggregability; (2) there is a weaker inverse relationship between clopidogrel response and pre-treatment platelet aggregability, and a significant inverse relationship between pre-treatment PGE1 response and pre-treatment platelet aggregability. Furthermore, pre-treatment PGE1 response also predicts on-treatment platelet aggregability in response to ADP at steady state. Thus, HTPA largely represents clopidogrel resistance.

Influence of Direct Thrombin Inhibitor and Low Molecular Weight Heparin on Platelet Function in Patients with Coronary Artery Disease: A Prospective Interventional Trial.

INTRODUCTION: The interaction between anticoagulants and platelet function is complex. Previous publications showed mixed results regarding the role of heparins in platelet aggregation. On the other hand, the direct thrombin inhibitor (DTI) dabigatran might enhance the risk of myocardial infarction in patients with atrial fibrillation, which could be related to increased platelet aggregability. METHODS: This was a prospective, interventional study of patients with chronic coronary artery disease (CAD) taking low-dose aspirin. The objective of the current study was to compare the effects of dabigatran versus enoxaparin on platelet aggregability. Subjects initially were on orally administered dabigatran for 5 days followed by subcutaneously administered enoxaparin after a 30-day washout period. Platelet function was assessed at baseline and after each intervention by multiple electrode aggregometry (MEA-ASPI) (primary endpoint), serum thromboxane B2 (TXB2), VerifyNow Aspirin™, and coagulation tests (secondary endpoints). RESULTS: Compared to baseline MEA-ASPI values, dabigatran increased platelet aggregation while enoxaparin decreased platelet aggregation (+ 5 U ± 24.1 vs - 6 U ± 22.2, respectively, p = 0.012). The TXB2 assay showed the same pattern (+ 2 pg/ml for dabigatran vs - 13 pg/ml for enoxaparin, p = 0.011). None of the additional tests showed significant differences between the groups. Individually, compared to baseline TXB2 results, enoxaparin significantly decreased platelet activation [33 (16.5-95) pg/mL vs 20 (10-52) pg/mL, respectively, p = 0.026], but no significant differences were observed with dabigatran. CONCLUSIONS: DTI and anti-Xa drugs exert opposite effects on platelet function. A significant decrease in platelet activation through COX1 (also known as prostaglandin G/H synthase 1) was observed with enoxaparin, but no significant differences in platelet function were observed with dabigatran. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02389582.

Coronary blood flow volume change is negatively associated with platelet aggregability in patients with non-obstructive ischemic heart disease who have no anti-platelet agents.

BACKGROUND: Thrombus formation is one of the main pathogeneses of acute coronary syndrome with atherosclerotic rupture. Previous studies have reported that atherosclerosis increases platelet aggregability and that vascular endothelial dysfunction reflects early change of atherosclerosis. However, the relationship between coronary endothelial dysfunction and platelet reactivity remains unclear. Therefore, in this study, we investigated the relationship between them in non-obstructive ischemic heart disease (IHD) patients. METHODS: Three hundred sixty-eight consecutive stable patients with suspected angina presenting non-obstructive coronary arteries (<50% diameter) in coronary angiography were investigated with the intracoronary acetylcholine provocation test and measured adenosine triphosphate-induced coronary flow reserve. Finally, 25 non-obstructive IHD patients who had no anti-platelet agents were assessed for the relationship between coronary blood flow volume (CBFV) change and platelet aggregability as P2Y12 reaction unit (PRU) by VerifyNow P2Y12 assay system. RESULTS: CBFV change by intracoronary 20 µg/kg per minute acetylcholine provocation showed a significant negative correlation with platelet aggregability as PRU (r = 0.44, P = 0.03). Conversely, there was no significant correlation between PRU and endothelial function as coronary flow reserve. Furthermore, multivariable linear regression analysis indicated that an incremental CBFV change was independently associated with PRU (ß = 0.63, P < 0.001) in non-obstructive IHD patients. CONCLUSIONS: In patients with non-obstructive IHD, CBFV change was significantly associated with platelet aggregability, indicating that coronary endothelial dysfunction might mediate higher platelet aggregability.