Effect of aspirin treatment in patients with peripheral arterial disease monitored with the platelet function analyzer PFA-100

Abstract

We have used the platelet analyzer PFA-100TM to assess the effect of aspirin (ASA) in patients with documented peripheral arterial disease (PAD). Thirty-one previously untreated patients were recruited. Laboratory investigations, including the collagen and adenosine diphosphate closure time (CADP-CT) and the collagen and epinephrine closure time (CEPI-CT) were performed before and 7 days after treatment with 100 mg ASA per day. Five patients were excluded from the final analysis: one patient did not appear for second examination, in one patient type I von Willebrand disease was diagnosed, and three patients with prolonged CEPI-CT admitted the intake of non-steroidal anti-inflammatory drugs. Prior to ASA treatment, CADP-CT was 90 +/- 15 s (range, 67-124 s) and CEPI-CT was 116 +/- 27 s (range, 78-164 s). There was a significant negative correlation between CADP-CT and von Willebrand factor antigen (r = -0.57, P = 0.001). After treatment with 100 mg ASA per day, CADP-CT was not significantly different (96 +/- 22 s; range, 65-158 s). CEPI-CT, however, was prolonged in all patients, compared with pre-ASA values (226 +/- 82 s; range, 89 to > 300 s). In 12 of 26 patients, CEPI-CT was > 300 s and in another four of 26 patients CEPI-CT was prolonged to more than the upper normal range ('responders'). In the remaining 10 patients, CEPI-CT values did not exceed the upper limit of the normal range ('non-responders'). Five non-responders were re-investigated after intake of 300 mg ASA per day for 3 weeks; in none of these was a CEPI-CT > 165 s recorded. We conclude that 40% of PAD patients have an inadequate response to ASA, as determined by the PFA-100TM CEPI-CT. Whether these patients have a reduced benefit from this treatment remains to be investigated.

Variation in Platelet Function Testing Has a Major Influence on Detection of Aspirin Resistance in Healthy Subjects

“…As observed before [8,20,21] , aspirin significantly prolonged CEPI closure time and had no significant effect on CADP closure time in this study. According to CEPI closure time, 20% of subjects were aspirin resistant on both days after aspirin.…”

Aspirin and Clopidogrel

“…As a matter of fact, Chakroun et al recently showed that high plasma VWF levels are the main determinant of short PFA-100 closure time in patients with cardiovascular disease on aspirin treatment, 61 and Watala et al demonstrated that VWF interaction with GPIb and GPIIb/IIIa is the major determinant of PFA-100 closure time, whereas other platelet receptors and mechanisms leading to platelet aggregation are of minor significance. 63 These findings explain the relatively high prevalence of short PFA-100 closure time in patients on aspirin treatment for cardiovascular or cerebrovascular disease, 42,43,[57][58][59][60][61][62] because these patients tend to have higher than normal levels of plasma VWF. Therefore, because aspirin does not inhibit the major determinants of the PFA-100 closure time, it appears that the PFA-100 system is not an adequate method to measure platelet inhibition by aspirin.…”

“…This could easily account for the high percentage of subjects with short closure time despite being on aspirin treatment. 42,43,[57][58][59][60][61][62] Because the PFA-100 system studies platelet function under flow conditions that are characterized by high shear, plasma VWF is a major determinant of closure time. As a matter of fact, Chakroun et al recently showed that high plasma VWF levels are the main determinant of short PFA-100 closure time in patients with cardiovascular disease on aspirin treatment, 61 and Watala et al demonstrated that VWF interaction with GPIb and GPIIb/IIIa is the major determinant of PFA-100 closure time, whereas other platelet receptors and mechanisms leading to platelet aggregation are of minor significance.…”

Frequency of development of aspirin resistance in the early postoperative period and inadequate inhibition of thromboxane A2 production after coronary artery bypass surgery

“…Grundmann et al [8] used PFA-100 in 35 symptomatic patients with asymptomatic cerebrovascular disease, who received 100 mg aspirin daily, and found that aspirin resistance developed in 34% of symptomatic patients and 0% of asymptomatic patients. Roller et al [9] determined the threshold value of Col/Epi closure time as 165 sec for the diagnosis of aspirin resistance and found the percentage of aspirin resistance to PFA-100 as 40%. Macchi et al [10] reported a threshold value for Col/Epi closure time of 186 sec for the diagnosis of aspirin resistance, and reported that in patients with stable angina pectoris disease, who received 160 mg aspirin daily, 29.2% developed aspirin resistance according to PFA-100.…”