Impact of aspirin and clopidogrel interruption on platelet function in patients undergoing major vascular surgery.

AIMS: To investigate functional platelet recovery after preoperative withdrawal of aspirin and clopidogrel and platelet function 5 days after treatment resumption. METHODS/RESULTS: We conducted an observational study, which prospectively included consecutive patients taking aspirin, taking clopidogrel, and untreated controls (15 patients in each group). The antiplatelet drugs were withdrawn five days before surgery (baseline) and were reintroduced two days after surgery. Platelet function was evaluated by optical aggregation in the presence of collagen, arachidonic acid (aspirin) and ADP (clopidogrel) and by VASP assay (clopidogrel). Platelet-leukocyte complex (PLC) level was quantified at each time-point. At baseline, platelet function was efficiently inhibited by aspirin and had recovered fully in most patients 5 days after drug withdrawal. PLC levels five days after aspirin reintroduction were similar to baseline (+4±10%; p = 0.16), in line with an effective platelet inhibition. Chronic clopidogrel treatment was associated with variable platelet inhibition and its withdrawal led to variable functional recovery. PLC levels were significantly increased five days after clopidogrel reintroduction (+10±15%; p = 0.02), compared to baseline. CONCLUSIONS: Aspirin withdrawal 5 days before high-bleeding-risk procedures was associated with functional platelet recovery, and its reintroduction two days after surgery restored antiplaletet efficacy five days later. This was not the case of clopidogrel, and further work is therefore needed to define its optimal perioperative management

Flowchart of the study.

<p>Flowchart of the study.</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

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

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