In vitro bleeding test with PFA-100-aspects of controlling individual acetylsalicylic acid induced platelet inhibition in patients with cardiovascular disease.

OBJECTIVES: This study investigated the usefulness and practicability of a platelet function analyzer (PFA-100(TM), DADE-Behring, Germany) to determine individual platelet inhibition in patients treated with acetylsalicylic acid (ASA).
BACKGROUND: Patients with coronary artery disease (CAD) routinely and during angioplasty (PTCA) receive standard doses of ASA to avoid acute coronary syndromes and abrupt vessel closures without information of the individual efficacy of platelet inhibition.
METHODS: With the PFA-100(TM) a standardized bleeding time is measured. Whole-blood anticoagulated with 3.2% sodium citrate is aspirated through a capillary ( solidus in circle 200 microm) and through an aperture ( solidus in circle 147 microm). The time until occlusion of the aperture (closure time, CT) by a stable platelet plug induced by shear stress, collagen and epinephrine (COLL/EPI-CT) or shear stress, collagen and adenosine 5'-diphosphate (COLL/ADP-CT) is determined. To examine the usefulness of the PFA-100(TM) as a rapid bedside test and the individual effect of ASA, closure time was measured in healthy individuals (n=17), in patients with stable CAD (n=19) and in patients undergoing PTCA (n=8).
RESULTS: Patients with stable CAD and regular medication with 100 mg ASA per day for at least 3 month showed shorter COLL/ADP-CT in comparison to healthy individuals who took only one single dose of 100 mg ASA. Of the patients with CAD 63% had a COLL/EPI-CT within normal range suggesting a low or no response to ASA. Also only 50% of the patients undergoing PTCA reached the expected COLL/EPI-CT>300 s after an additive single dose of 500 mg ASA intravenously. Neither heparin, phenprocoumon, sex nor different blood sampling methods seem to influence the measurements relevantly.
CONCLUSIONS: This pilot study indicates that with the PFA-100(TM) test device a simple and quick measurement of an in vitro bleeding time is possible. It is able to detect an increase in the bleeding time after a single dose of ASA 100 mg in healthy subjects, reflecting a sensitive detection of ASA induced changes in platelet inhibition respective activation. Differences in the individual response to ASA could be observed in healthy subjects, patients with stable CAD and patients undergoing PTCA. Further studies should validate the PFA-100(TM) with standard methods to determine ASA response in patients with cardiovascular disease and investigate implications for treatment and outcome in this patient group.