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Acetaminophen Inhibits Platelet Function Dose-dependently in Volunteers
Abstract number: P1546
Munsterhjelm1 E, Lundström1 NM, Niemi1 TT, Neuvonen2 PJ, Rosenberg1 PH
11Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Hospital, Finland 11Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Hospital, Finland 22Department of Clinical Pharmacology, Helsinki University Hospital, Finland
Background: Acetaminophen (paracetamol) is a widely used analgesic, traditionally considered not to influence platelet function. Methods: 13 healthy, non-smoking volunteers participated in this double-blind, randomized, placebo-controlled, cross-over study. Volunteers were given intravenously acetaminophen 15 mg kg-1; 22.5 mg kg-1; 30 smg kg-1 or placebo and platelet aggregation was assessed photometrically before drug administration and after 10 minutes and 90 minutes. Aggregation in platelet rich plasma was induced with arachidonic acid (0.5 mM), which is transformed into pro-aggregatory thromboxane A2 by cyclo-oxygenase 1. Plasma concentrations of acetaminophen were determined with HPLC. Results: | | Mean plasma concentration (mg l-1) of acetaminophen (95% CI) | Median platelet aggregation (% of pre-drug value) (25th/75th percentiles) |
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| 10 min | 90 min | 10 min | 90 min |
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| Placebo | 0 | 0 | 104 (99/106) | 101 (98/104) | | 15 mg kg-1 | 18.2 (16.3–20.1) | 10.5 (9.6–11.4) | 90 (2.1/92)* | 91 (3.2/99)* | | 22.5 mg kg-1 | 30.2 (27.5–33.0) | 16.3 (14.8–17.8) | 4.6 (3.2/7.4)* | 55 (3.8/96)* | | 30 mg kg-1 | 39.1 (34.9–43.4) | 22.2 (20.5–24.0) | 2.9 (1.5/6.0)* | 8.6 (2.9/89)* | | *P < 0.05 vs placebo (Wilcoxon matched pairs signed rank sum test with Bonferroni-correction) |
Discussion: The analgesic plasma concentration of acetaminophen is not known. However, the well-known antipyretic concentration of 10–20 mg l-1 was reached after all doses in the present study. Platelet aggregation was dose-dependently and significantly inhibited by acetaminophen. This antiaggregatory effect of acetaminophen may play a clinical role in patients with intrinsic or drug-induced impaired hemostasis.
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