Effect of DPQ and INO-1001 on ADP-, collagen- or PAR1ap-induced platelet aggregation.

<p>Human PRP samples were pre-incubated with PARP inhibitor (50 µM) or its vehicle and then stimulated with ADP (1.5 to 5 µM; to produce a biphasic aggregation curve), collagen (1 to 2 µg/ml) or PAR1ap (1 to 2 µM). Results are expressed relatively to platelet agonist alone ( = vehicle group; normalized to 100%) and presented as the mean ± SD (n = 5–6).</p

Effect of PJ34 on both phases of ADP-induced platelet aggregation.

<p>(A) ADP concentration (1.5 to 5 µM) was determined for each donor to produce a biphasic aggregation curve. (B) Human PRP samples were pre-incubated with PJ34 (1–100 µM) or its vehicle and then stimulated with ADP. Results are expressed relatively to ADP alone ( = vehicle group; normalized to 100%) and presented as the mean ± SD (n = 6–7). **P<0.01 and ***P<0.001 <i>versus</i> the corresponding vehicle group (one-way ANOVA followed by Dunnett's test). (C) Representative curves showing the effect of PJ34 or its vehicle on platelet aggregation induced by 2 µM ADP.</p

Effect of incremental concentrations of ADP on platelet aggregation in the presence of PJ34.

<p>Human PRP samples were pre-incubated with PJ34 or its vehicle and then stimulated with ADP. Results are expressed relatively to ADP alone ( = vehicle group; normalized to 100%) and presented as the mean ± SD (n = 4–7). *P<0.05, **P<0.01 and ***P<0.001 <i>versus</i> the corresponding vehicle group (one-way ANOVA followed by Dunnett's test).</p

Effect of PJ34 on VASP phosphorylation.

<p>Human whole blood was pre-incubated with PJ34 or its vehicle and then stimulated with ADP. A low platelet reactivity index (PRI) is associated with a high VASP phosphorylation state and thus reflects P2Y₁₂ inhibition. Results are expressed relatively to ADP alone ( = vehicle group) and presented as the mean ± SD (n = 3–4). **P<0.01 and ***P<0.001 <i>versus</i> vehicle (one-way ANOVA followed by Dunnett's test).</p

Effect of PJ34 on collagen- and PAR1ap-induced platelet aggregation.

<p>Human PRP samples were pre-incubated with PJ34 or its vehicle and then stimulated with either collagen (1 to 2 µg/ml) or PAR1ap (1 to 2 µM). Results are expressed relatively to platelet agonist alone ( = vehicle group; normalized to 100%) and presented as the mean ± SD (n = 7–8).</p

Impact of aspirin withdrawal and reintroduction on arachidonic acid-induced platelet aggregation.

<p>D-5: baseline value determined during preoperative examination. Ds: day of surgery. D+7: seven days after surgery, five days after aspirin resumption Arachidonic acid was used at 2 mM. Platelet aggregation is expressed as maximal aggregation (%).</p

Flowchart of the study.

<p>Flowchart of the study.</p

Platelet-Leukocyte Complex (PLC) levels in the three patient groups.

<p>PLC are expressed as a percentage of total leukocytes. D-5: baseline value for aspirin and clopidogrel groups. Ds: day of surgery, baseline value for the control group. D+7: seven days after surgery, five days after aspirin or clopidogrel 75 mg resumption.</p

Impact of clopidogrel withdrawal and reintroduction on platelet functions.

<p>A: Platelet aggregation response to 20 µM ADP, expressed as maximal aggregation (%). B: VASP phosphorylation level, expressed as the Platelet Reactivity Index (%). D-5: baseline value; Ds: day of surgery; D+7: seven days after surgery, five days after clopidogrel 75 mg resumption.</p

Patients’ characteristics.

<p>Data are presented as the mean value ± SD or number (%) of subjects. RCRI: Revised Cardiac Risk Index; ACE: angiotensin converting enzyme. CI = confidence interval.</p