Inconsistency of different methods for assessing ex vivo platelet function: relevance for the detection of aspirin resistance

• Published in: Haematologica (Roma) Vol. 95; no. 12; pp. 2095 - 2101
• Main Authors: RENDA, Giulia, ZURRO, Maria, MALATESTA, Gelsomina, RUGGIERI, Benedetta, DE CATERINA, Raffaele
• Format: Journal Article
• Language: English
• Published: Pavia Ferrata Storti Foundation 01.12.2010
• Subjects: Adenosine Diphosphate - pharmacology; Adult; Arachidonic Acid - pharmacology; Aspirin - pharmacology; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - physiology; Collagen - pharmacology; Drug Resistance; Female; Hematologic and hematopoietic diseases; Humans; Male; Medical sciences; Middle Aged; Original; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Platelet Function Tests - methods; Thromboxane B2 - blood; Young Adult; Prostaglandin-endoperoxide synthase; Hematology; aspirin resistance; Enzyme; Arachidonic acid derivatives; Enzyme inhibitor; Thromboxane B2; Acetylsalicylic acid; Method; Antiplatelet agent; platelet aggregation; Aggregation; Resistance; Platelet; Ex vivo; Hemostasis; Eicosanoid; Platelet function; Serum; serum thromboxane B2; Oxidoreductases; Salicylates; Diagnosis
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2010.027102

Assays to evaluate platelet function are often interchangeably used to assess "resistance" to aspirin. We compared different platelet function assays in patients treated or untreated with aspirin. Platelet function was evaluated in 162 subjects, 85 of whom were not being treated with any antiplatelet drug and 77 of whom were receiving chronic therapy with low-dose aspirin. Platelet Function Analyzer collagen/ADP- and collagen/epinephrine closure times, as well as light transmittance aggregometry in response to ADP, collagen and arachidonic acid (this last in 47 aspirin-treated patients) were determined. In 43 aspirin-treated patients, serum thromboxane B(2) levels were also measured. In untreated patients, collagen/ADP- and collagen/epinephrine-closure times were correlated with each other (r=0.5, P=0.0001), but did not correlate with ADP- or collagen-induced aggregation. In patients treated with aspirin, collagen/ADP-closure time values were not different from those in untreated patients, while the collagen/epinephrine-closure time was prolonged. ADP-induced aggregation was unaffected by aspirin, while collagen-induced aggregation was reduced. Arachidonic acid-induced aggregation was almost completely suppressed (% maximum light transmittance aggregometry =5 ± 13%). There was, however, no correlation between the various platelet function tests. Serum thromboxane B(2), an index of platelet cyclooxygenase-1 activity, was almost completely suppressed (down to 8 ± 17 ng/mL) in treated patients, and was not correlated with arachidonic acid-, ADP- and collagen-induced aggregation or with collagen/ADP-closure time, but was inversely correlated with collagen/epinephrine-closure time. There is a high heterogeneity of results of tests evaluating inhibition of platelet function by aspirin, and the results of functional tests do not match biochemical measurement of cyclooxygenase-1 activity. Extreme caution should, therefore, be used in defining "resistance" to aspirin on the basis of the results of these tests.