To cite this article: Linnemann B, Schwonberg J, Mani H, Prochnow S, Lindhoff-Last E. Standardization of light transmittance aggregometry for monitoring antiplatelet therapy: an adjustment for platelet count is not necessary. J Thromb Haemost 2008; 6: 677-83.Summary. Background: Light transmittance aggregometry (LTA) is considered to be the Ôgold standardÕ of platelet function testing. As LTA has been poorly standardized, we analyzed the results of LTA in healthy subjects and patients with antiplatelet therapy using different concentrations of agonists and performing tests in non-adjusted and platelet count-adjusted platelet-rich plasma (PRP). Methods: LTA was performed in 20 healthy subjects and in patients treated with aspirin (n = 30) or clopidogrel (n = 30) monotherapy, as well as in patients on combination therapy (n = 20), using arachidonic acid (ARA 0.25 and 0.5 mg mL ) and adenosine diphosphate (ADP 2 and 5 lM) as agonists and performing platelet function tests in non-adjusted and platelet count (250 nL )1 ± 10%)-adjusted PRP. Results: The overall platelet aggregation response is decreased after adjusting the PRP for platelet count compared with measurements in unadjusted PRP. The variability of aggregation results is high in adjusted PRP in the subgroup of healthy subjects, ranging from 9.2-95.3% (5th-95th percentile) relative to 77.6-95.5% in nonadjusted PRP when determining maximum aggregation to ARA 0.5 mg mL )1. Late aggregation using ADP 2 lM ranges from 3.8-89.9% in adjusted PRP compared with 42.9-92.5% in non-adjusted PRP. Maximum aggregation using ARA 0.5 mg mL )1 in non-adjusted PRP differentiates between aspirin-treated patients and healthy controls well, whereas late aggregation using ADP 2 lM in non-adjusted PRP offers the best discrimination between clopidogrel-treated patients and healthy controls. Conclusion: Adjustment of PRP for platelet count does not provide any advantage and therefore the time-consuming process of platelet count adjustment is not necessary.

Edelgard Lindhoff-Last. Variability of non-response to aspirin in patients with peripheral arterial occlusive disease during long-term follow-up. Annals of Hematology, Springer Verlag, 2009, 88 (10) Abstract Non-responsiveness to aspirin as detected by laboratory tests may identify patients at high risk for future vascular events. The aim of this prospective study was to evaluate whether non-responsiveness to aspirin is stable over time. Ninety-eight patients with stable peripheral arterial occlusive disease (PAOD) treated with 100 mg/d aspirin were followed over a median timeframe of 17 months. Platelet function tests were performed initially and at follow-up using arachidonic acid-induced light transmittance aggregometry (LTA) in native platelet-rich plasma with the Behring Coagulation Timer® and by measuring the collagen−epinephrine closure time (CT) on a Platelet Function Analyzer (PFA-100®). When determining platelet function using LTA, four patients (4.1%) had residual platelet function (i.e., MaxAggr ≥78%) despite aspirin treatment, whereas, according to the PFA-100® results, 12 patients (12.2%) were identified as nonresponders (i.e., CT <192 s). Fifty-seven patients who were still under treatment with 100 mg/d aspirin at the time of follow-up provided a second blood sample. Further platelet function tests with the PFA-100® system identified a persistent non-responsiveness to aspirin over time in three patients (5.3%) whereas four (7.0%) and 15 (26.3%) patients had changes in response status when platelet function was assessed by LTA and on the PFA-100®, respectively. We conclude that true non-responsiveness to aspirin is a rare phenomenon in stable PAOD patients.Furthermore, we conclude that in a number of patients, aspirin non-responsiveness is not stable over time.