Variables influencing Platelet Function Analyzer‐100^TM closure times in healthy individuals

Abstract

Summary We investigated the relationship between platelet function analyzer (PFA‐100TM) closure times (CT) and bleeding time (BT), platelet aggregation (PA) induced by ADP, arachidonic acid, and collagen, blood cell counts, and von Willebrand factor (VWF) in 120 well‐characterised healthy individuals. Pre‐analytical and analytical conditions were standardised comprehensively. In a substantial number of cases the differences between duplicate measurements exceeded 15%. The reference range (5th and 95th percentiles) for CT with the collagen/epinephrine (CEPI) and the collagen/ADP (CADP) cartridge was 93–223 s and 64–117 s respectively. Re‐examination of 11 individuals with CEPI‐CT above the 95th percentile revealed considerable batch‐to‐batch variation of CEPI‐CT. Males had significantly longer CADP than females (P = 0·002). CEPI and CADP‐CT measured pm were significantly longer than corresponding values determined am (P = 0·003 and P < 0·0001 respectively). Blood group O was associated with greater CEPI and CADP‐CT and lower VWF levels compared with non‐O blood groups (P = 0·008, P = 0·0003 and P < 0·0001 respectively). Linear regression analysis revealed association between CEPI‐CT, CADP‐CT and VWF (P < 0·0001), but no relationship was found between CT and BT or between CT and PA. We conclude that VWF plasma levels modulate PFA‐100TM CT to a greater extent than platelet function. Establishment of reliable reference ranges and careful standardisation of pre‐analytical and analytical conditions is a prerequisite for obtaining reliable PFA‐100TM results. Duplicate measurements are necessary.

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

“…It has been reported that the appropriate agonist concentration seems to be one of the important variables influencing platelet aggregation results [6] and this issue requires further investigation, especially in the context of aspirin resistance. Contrary to some previous reports [6,16] , aspirin had no effect on collagen-induced platelet aggregation in this study. Collagen has been recognized as less specific for measuring aspirin response, since collageninduced platelet activation is not dependent only on platelet production of thromboxane A 2 , but also on platelet reactivity to collagen and platelet responsiveness to secreted ADP [13,17] , and our results seem to support these data.…”

“…Even higher proportions of aspirin-resistant subjects were detected if only a single measurement was considered, namely 30% for 1A+ and 35% for 2A+, which is in accordance with published data, where a single measurement was also considered [19,22] . Variation of CEPI and CADP closure times without aspirin were in accordance with the data provided by the manufacturer and with the published data [16,20] . Although the median within-subject variation of CEPI closure time after aspirin was similar to the variation without aspirin, the range of variations after aspirin was much wider and exceeded 30% in one quarter of subjects.…”

The Impact of Aspirin Resistance on the Long‐term Cardiovascular Mortality in Patients with Non‐ST Segment Elevation Acute Coronary Syndromes

“…On the other hand, PFA-100 is a simple, rapid, and widely available pointof-care method, which has been designed to overcome many drawbacks of other available techniques, such as standard platelet aggregometry or flow cytometry. Second, it has been shown that the values of PFA-100 CEPI-CT are highly dependent on the von Willebrand factor, 10 and it is possible that differences in von Willebrand factor levels (not measured in the present study) could, at least partially, account for the outcome differences between aspirin sensitives and aspirin resistants. However, Fucsh et al, in a study of patients with ACS, have shown that inclusion of von Willebrand factor levels in a multivariate Cox regression model did not alter the predictive value of a low PFA-100 CEPI-CT for the incidence of long-term recurrent instability.…”

“…10 Previous studies, using several methods for the assessment of aspirin resistance, evaluated the possible clinical relevance of this phenomenon in patients with atherothrombotic complications. 1 -9 Grotemeyer et al, in a study of 180 patients suffering from ischemic stroke, have demonstrated that long-term fatal or nonfatal cardiovascular events were significantly more frequent in aspirin resistants than in aspirin sensitives.…”

Nachblutungen und Gerinnungsstörungen bei Tonsillektomien

“…Scheckenbach et al [21] sowie Schwerdtfeger u. Dennebaum [25] sehen in der Bestimmung der Blutungszeit kein Routineverfahren, sondern eine gezielt eingesetzte Diagnostik bei anamnestischem oder klinischem Hinweis auf eine Thrombozytenfunktionsstörung. Wir würden uns den letzten Autoren anschließen, da auch die In-vitro-Testung der Blutungszeit mit PFA kostenaufwendig ist und, wie Haubelt et al beschreiben [8], Limitationen zeigt und insofern nur bei Verdacht auf eine Gerinnungsstörung eingesetzt werden sollte. …”