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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Burroughs, S. F. Articles by Johnson, G. J. Search for Related Content PubMed PubMed Citation Articles by Burroughs, S. F. Articles by Johnson, G. J. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Beta-lactam antibiotic-induced platelet dysfunction: evidence for irreversible inhibition of platelet activation in vitro and in vivo after prolonged exposure to penicillin SF Burroughs and GJ Johnson Hematology/Oncology Section, Veterans Affairs Medical Center, Minneapolis, MN 55417. beta-Lactam antibiotics cause platelet dysfunction with bleeding complications. Previous in vitro studies documented reversible inhibition of agonist-receptor interaction. This mechanism is inadequate to explain the effect of beta-lactam antibiotics in vivo. Platelet function does not return to normal immediately after drug treatment, implying irreversible inhibition of platelet function. We report here evidence of irreversible platelet functional and biochemical abnormalities after in vitro and in vivo exposure to beta- lactam antibiotics. Irreversible binding of [14C]-penicillin (Pen) occurred in vitro. After 24 hours' in vitro incubation with 10 to 20 mmol/L Pen, or ex vivo after antibiotic treatment, irreversible functional impairment occurred; but no irreversible inhibition of alpha 2 adrenergic receptors, measured with [3H]-yohimbine, or high-affinity thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors, measured with agonist [3H]-U46619 and antagonist [3H]-SQ29548, occurred. However, low- affinity platelet TXA2/PGH2 receptors were decreased 40% after Pen exposure in vitro or in vivo, indicating irreversible membrane alteration. Two postreceptor biochemical events were irreversibly inhibited in platelets incubated with Pen for 24 hours in vitro or ex vivo after antibiotic treatment. Thromboxane synthesis was inhibited 28.3% to 81.7%. Agonist-induced rises in cytosolic calcium ([Ca2+]i) were inhibited 40.1% to 67.5% in vitro and 26.6% to 52.2% ex vivo. Therefore, Pen binds to platelets after prolonged exposure, resulting in irreversible dysfunction attributable to inhibition of TXA2 synthesis and impairment of the rise in [Ca2+]i. The loss of low- affinity TXA2/PGH2 receptors suggests that the primary site of action of these drugs is on the platelet membrane. Volume 75, Issue 7, pp. 1473-1480, 04/01/1990 Copyright © 1990 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. M. BRINSON, P. G. NOONE, M. A. MAURO, M. R. KNOWLES, J. R. YANKASKAS, J. S. SANDHU, and P. F. JAQUES Bronchial Artery Embolization for the Treatment of Hemoptysis in Patients with Cystic Fibrosis Am. J. Respir. Crit. Care Med., June 1, 1998; 157(6): 1951 - 1958. [Abstract] [Full Text] [PDF]

	Copyright © 1990 by American Society of Hematology         Online ISSN: 1528-0020