In vitro aspirin resistance detected by PFA-100 closure time: pivotal role of plasma von Willebrand factor

The in vitro closure time (CT), determined by the Platelet Function Analyzer (PFA-100), is used to monitor patients treated with aspirin. A relatively high percentage of in vitro aspirin resistance was reported despite an adequate inhibition of platelet response to arachidonic acid and we investigated whether high plasma levels of von Willebrand factor ristocetin cofactor activity (vWF:RCo) may contribute to this profile. Platelet aggregation test, CT [collagen adrenaline (CEPI-CT) and collagen adenosine 5'-diphosphate (ADP) (CADP-CT)], and vWF:RCo levels were evaluated in 55 consecutive patients receiving aspirin (75-250 mg/d) versus 32 untreated control subjects. All the aspirin-treated patients showed platelet aggregation responses that reflected the aspirin intake. However, CT data analysis enabled aspirin good-responder (GR) and aspirin bad-responder (BR) patients to be identified. All GR group subjects (n = 27), had a CEPI-CT and a CADP-CT longer than 300 s and 96 s respectively. The BR group (n = 28) had CEPI-CT values below 200 s and all CADP-CT were in the normal range (77 +/- 19 s). Interestingly, the BR plasma vWF:RCo levels were significantly higher (159 +/- 43%) than those of the GR group (121 +/- 34%) (P < 0.01), which were similar to control values (114 +/- 31%). A negative correlation between vWF:RCo and CT values was established. We demonstrate that in vitro aspirin-resistance, revealed by PFA-100 CT prolongation failure, is correlated to increased plasmatic vWF:RCo levels, reinforcing its particular importance in PFA-100 cartridges performance.