Background Platelet P2Y12 antagonist ticagrelor reduces mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets, leukocytes, and endothelial cells release proinflammatory and prothrombotic extracellular vesicles (EVs), we hypothesized that the release of EVs is more efficiently inhibited by ticagrelor compared to clopidogrel. Objectives We compared EV concentrations and EV procoagulant activity in plasma of patients after AMI treated with ticagrelor or clopidogrel. Methods After percutaneous coronary intervention, 60 patients with first AMI were randomized to ticagrelor or clopidogrel. Flow cytometry was used to determine concentrations of EVs from activated platelets (CD61+, CD62p+), fibrinogen+, phosphatidylserine (PS+), leukocytes (CD45+), endothelial cells (CD31+, 146+), and erythrocytes (CD235a+) in plasma at randomization, after 72 hours and 6 months of treatment. A fibrin generation test was used to determine EV procoagulant activity. Results Concentrations of platelet, fibrinogen+, PS+, leukocyte, and erythrocyte EVs increased 6 months after AMI compared to the acute phase of AMI (P ≤ .03). Concentrations of platelet EVs were lower on ticagrelor compared to clopidogrel after 6 months (P = .03). Concentrations of fibrinogen+, PS+, and leukocyte EVs were lower on ticagrelor compared to clopidogrel both after 72 hours and 6 months (P ≤ .03). Concentrations of endothelial EVs and EV procoagulant activity did not differ between patient groups and over time (P ≥ .17). Conclusions Ticagrelor attenuates the increase of EV concentrations in plasma after acute myocardial infarction compared to clopidogrel. The ongoing release of EVs despite antiplatelet therapy might explain recurrent thrombotic events after AMI and worse clinical outcomes on clopidogrel compared to ticagrelor.

Inhibition of P2Y1 and P2Y12 receptors reduces platelet aggregation and affects the release of distinct subpopulations of PEVs. Ticagrelor decreases the release of procoagulant PEVs from activated platelets, which may contribute to the observed clinical benefits in patients treated with ticagrelor.

(1) Background: Prostacyclin analogues (epoprostenol, treprostinil, and iloprost) induce vasodilation in pulmonary arterial hypertension (PAH) but also inhibit platelet function. (2) Objectives: We assessed platelet function in PAH patients treated with prostacyclin analogues and not receiving prostacyclin analogues. (3) Methods: Venous blood was collected from 42 patients treated with prostacyclin analogues (49.5 ± 15.9 years, 81% female) and 38 patients not receiving prostacyclin analogues (55.5 ± 15.6 years, 74% female). Platelet reactivity was analyzed by impedance aggregometry using arachidonic acid (AA; 0.5 mM), adenosine diphosphate (ADP; 6.5 µM), and thrombin receptor-activating peptide (TRAP; 32 µM) as agonists. In a subset of patients, concentrations of extracellular vesicles (EVs) from all platelets (CD61+), activated platelets (CD61+/CD62P+), leukocytes (CD45+), and endothelial cells (CD146+) were analyzed by flow cytometry. Platelet-rich thrombus formation was measured using a whole blood perfusion system. (4) Results: Compared to controls, PAH patients treated with prostacyclin analogues had lower platelet reactivity in response to AA and ADP (p = 0.01 for both), lower concentrations of platelet and leukocyte EVs (p ≤ 0.04), delayed thrombus formation (p ≤ 0.003), and decreased thrombus size (p = 0.008). Epoprostenol did not affect platelet reactivity but decreased the concentrations of platelet and leukocyte EVs (p ≤ 0.04). Treprostinil decreased platelet reactivity in response to AA and ADP (p ≤ 0.02) but had no effect on the concentrations of EVs. All prostacyclin analogues delayed thrombus formation and decreased thrombus size (p ≤ 0.04). (5) Conclusions: PAH patients treated with prostacyclin analogues had impaired platelet reactivity, EV release, and thrombus formation, compared to patients not receiving prostacyclin analogues.

controlled trial protocol to investigate the antiplatelet therapy effect on extracellular vesicles in acute myocardial infarction (AFFECT EV)', Platelets.

ABSTRACT:In this report, we present a rare case of cephalothoracopagus (monocephalic dithoracic) conjoined twins with anencephaly in pig. Conjoined Polish large white piglets were born at term after an uncomplicated birth. The litter consisted of 11 piglets. The conjoined twins were born alive, but died shortly after birth and were subjected to further investigation. Blood vessels of the heart were filled with LBS 3060 latex, and then the twins were fixed in 10% non-buffered formalin. Necropsy revealed the external and internal anatomy of the affected twins. Examinations demonstrated abnormalities of skeletal, digestive, cardiovascular, respiratory and nervous systems. The twins had a single head, neck and chest and were separated from the umbilicus caudally. They had four forelimbs and four hindlimbs. Examination of the skeleton revealed two complete vertebral columns connected with one skull. Two tongues and a cleft palate were present in the oral cavity. The conjoined twins had a single pharynx, oesophagus, stomach, duodenum, part of jejunum, spleen, liver and pancreas. The remaining part of the digestive system was doubled. Each piglet had a separate urogenital apparatus. The examination revealed only one heart with structural abnormalities. Two larynxes and tracheas were identified. The right twin had the right lung while the left twin had the left lung. To the authors' knowledge, this is the first detailed report of this type of conjoined twins in the pig.