Abstract Number: PB0473
Meeting: ISTH 2020 Congress
Background: Inhibition of serum thromboxane (TxB2) and arachidonic acid-induced platelet aggregation (AA-PA) are direct indicators of platelet COX-1inhibition by acetylsalicylic acid (ASA). It is widely believed that >95% TxB2 inhibition from baseline is essential for clinical efficacy of ASA.
Aims: To evaluate the relation between AA-PA, and serum TxB2, urinary 11-dehydro thromboxane B2 (u11-dh TxB2), and ASA and salicylic acid (SA) levels.
Methods: ASA effect was assessed serially over a 24-hour period at 10 timepoints in seventeen healthy volunteers either receiving a single dose of 162 mg chewed /swallowed or 50-100 mg inhaled ASA. AA-PA was measured using light transmittance aggregometry, serum TxB2 by liquid chromatography‐mass spectrometry (LC-MS), u11-dh TxB2 by ELISA, and plasma concentrations of ASA and SA were measured by LC-MS. Receiver operator characteristic (ROC) analysis was used to develop criterion for each test measure using the definition for complete ASA inhibition (AA-induced PA of < 5%).
Results: Baseline variability was more pronounced with serum TxB2 (5-95% CI, 31-680ng/mL) as compared to AA-PA (65-81%) and u11-dh TxB2 (1556-4440 pg/mg).
AA-PA of < 5% was reached within 2 min with inhaled ASA and 30 min with chewed/swallowed ASA. Based on ROC analysis both u11-dh TxB2 and ASA level were outstanding (AUC>0.9) whereas serum TxB2 inhibition was excellent (AUC 0.8-0.9) (Table 1). ROC based criterion for serum TxB2 to indicate complete ASA inhibition is >49% and for u11-dh TxB2 is 1520 pg/mg.
Conclusions: Our study results suggest that the definition of >95% inhibition of serum TxB2 to indicate platelet COX-1inhibition for clinical efficacy may be overestimated and should be re-considered in future investigations.
|Serum TxB2 Inhibition (%)||>49||0.82||96.4||64.3||<0.001|
|Serum TxB2 (ng/mL)||<100||0.76||86.2||67.7||<0.001|
|u11-dh TxB2 (pg/mg)||<1520||0.92||76.0||100||<0.001|
|Acetylsalicylic acid (ng/mL)||>264||0.92||87.7||93.5||<0.001|
|Salicylic acid (ng/mL)||>263||0.83||68.1||93.6||<0.001|
[ROC analysis of Test Measures]
To cite this abstract in AMA style:Bliden K, Tantry U, Ens G, Messbarger W, Chaudhary R, Gurbel P. Defining Acetylsalicylic Acid Responsiveness: Understanding the Relation between Thromboxane B2 Inhibition and Aggregation Induced by Arachidonic Acid [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/defining-acetylsalicylic-acid-responsiveness-understanding-the-relation-between-thromboxane-b2-inhibition-and-aggregation-induced-by-arachidonic-acid/. Accessed December 6, 2021.
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