Perioperative changes of response to antiplatelet medication in vascular surgery patients.

INTRODUCTION: Reduced antiplatelet activity of aspirin (ALR) or clopidogrel (CLR) is associated with an increased risk of thromboembolic events. The reported prevalence data for low-responders vary widely and there have been few investigations in vascular surgery patients even though they are at high risk for thromb-embolic complications. The aim of this prospective observational monocentric study was to elucidate possible changes in ALR or CLR after common vascular procedures. METHODS: Activity of aspirin and clopidogrel was measured by impedance aggregometry using a multiple electrode aggregometer (Multiplate®). Possible risk factors for ALR or CLR were identified by demographical, clinical data and laboratory parameters. In addition, a follow-up aggregometry was performed after completion of the vascular procedure to identify changes in antiplatelet response. RESULTS: A total of 176 patients taking antiplatelet medications aspirin and/or clopidogrel with peripheral artery disease (PAD) and/or carotid stenosis (CS) were included in the study. The prevalence of ALR was 13.1% and the prevalence of CLR was 32% in the aggregometry before vascular treatment. Potential risk factors identified in the aspirin group were concomitant insulin medication (p = 0.0006) and elevated C-reactive protein (CRP) (p = 0.0021). The overall ALR increased significantly postoperatively to 27.5% (p = 0.0006); however, there was no significant change in CLR that was detected. In a subgroup analysis elevation of the platelet count was associated with a post-procedure increase of ALR incidence. CONCLUSION: The incidence of ALR in vascular surgery patients increases after vascular procedures. An elevated platelet count was detected as a risk factor. Further studies are necessary to analyse this potential influence on patency rates of vascular reconstructions.

Which is the best anticoagulant for whole blood aggregometry platelet function testing? Comparison of six anticoagulants and diverse storage conditions.

Major hindrances of impedance aggregometry are caused by limited storage time and the requirement of ex vivo anticoagulation. Data on the influence of different anticoagulants and storage conditions are rare and incomplete. This study has systematically examined the influence of six different anticoagulants (sodium and lithium heparin, 20 µg/mL and 45 µg/mL r-hirudin, benzylsulfonyl-D-Arg-Pro-4-amidinobenzylamide (BAPA), and citrate) on the results of Adenosine 5'-diphosphate (ADP) and arachidonic acid (AA) induced measurements using multiple-electrode impedance aggregometer (MEA). Measurements were carried out in a time frame of 0 min up to 48 h after blood withdrawal. In addition, the influence of storage temperatures of 4°C and 37°C was evaluated. Results of ADP-induced tests significantly varied within the first 30 min in all tested anticoagulants, in citrated blood even within the first 60 min. They remained stable up to 2 h in 20 µg/mL r-hirudin and BAPA, 4 h in citrate, 8 h in 45 µg/mL r-hirudin, and lithium heparin and up to a maximum of 12 h in sodium heparin anticoagulated blood. The analysis of AA-induced tests revealed no significantly different results up to 6 h when BAPA was used, 8 h in lithium heparin, 20 µg/mL r-hirudin and citrate, 12 h in 45 µg/mL r-hirudin, and even 24 h in sodium heparin-anticoagulated samples. A storage temperature of either 4°C or 37°C in contrast to room temperature had a negative influence on the stability of results. In conclusion, sodium heparin and 45 µg/mL r-hirudin as anticoagulants guarantee the longest storage time for impedance aggregometry.

Upregulation of platelet CD40, CD40 ligand (CD40L) and P-Selectin expression in cigarette smokers: a flow cytometry study.

Cigarette smoking is a well known risk factor for cardiovascular disease with a great impact on mortality. Studies have linked smoking to inflammation, platelet activation and enhanced atherosclerosis. The present study investigated the activation and expression of proinflammatory markers on platelets obtained from smokers. The expression of P-selectin (CD62P) (as a marker of activation) and CD40/CD40L (as a marker for proinflammatory processes) were quantified in platelets by flow cytometry. Platelet-rich plasma was obtained from 34 apparent healthy volunteers (19 cigarette smokers, 15 age-matched control persons). Basal measurements and the response to stimulation with ADP and TRAP (10, 30, 100 micromol/l) were evaluated. Values given (mean fluorescence index, MFI) are mean +/- standard deviation. The basal values of platelet bound CD40 (3.20 +/- 0.50 vs. 2.71 +/- 0.28; P = 0.002), CD40L (1.10 +/- 0.12 vs. 0.95 +/- 0.12; P = 0.005) and P-selectin (0.70 +/- 0.21 vs. 0.55 +/- 0.11; P = 0.012) were significantly elevated in smokers as compared to controls. In addition, higher values were noted on stimulation with ADP or TRAP in smokers, although these different values were without statistical significance. According to our data cigarette smoking activates platelets (P-selectin expression) and stimulates the CD40-CD40L-pathway in otherwise healthy volunteers. These findings emphasize that cigarette smoking leads to a proinflammatory and prothrombotic state thus contributing to accelerated atherosclerosis.