Emanuela Falcinelli1, Alessia Iannone2, Anna Maria Mezzasoma1, Lavinia Amato2, Tiziana Fierro1, Giuseppe Guglielmini1, Carlo Cagini2, Paolo Gresele3. 1. Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Italy. 2. Department of Surgical and Biomedical Science, Section of Ophthalmology, University of Perugia, Perugia, Italy. 3. Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Italy. Electronic address: paolo.gresele@unipg.it.
Abstract
INTRODUCTION: The use of topical NSAIDs is frequent in ophthalmology to reduce the local inflammatory reaction resulting from surgical procedures. Ocular use of some drugs was previously found to lead to significant systemic absorption with possible systemic effects. NSAIDs may enhance the hemorrhagic risk of anticoagulant and antiplatelet drugs. Aim of our study was to evaluate the systemic effects of two NSAIDs given by eyedrops on platelet COX-1 and on ex vivo and in vivo platelet activation. MATERIALS AND METHODS: 20 patients planned to undergo cataract surgery were randomized to the use of an ophthalmic solution containing Diclofenac or Indomethacin. Blood was taken at enrollment (baseline) and after 3 days of therapy (1 drop, 4 times a day). Arachidonic Acid (AA)-induced light transmission aggregometry (LTA), PFA-100®C-EPI, circulating platelet P-Selectin expression by flow cytometry and serum and AA-induced TxB2 production were evaluated before and after eyedrop therapy. RESULTS: AA (0.1-0.2 mM)-induced LTA was significantly reduced after ocular indomethacin but not after diclofenac. PFA-100®C-EPIclosure time was also significantly prolonged in the indomethacin group but not in the diclofenac group. Circulating platelet P-selectin expression was significantly reduced after treatment with indomethacin compared with diclofenac. Finally, treatment with eyedrop indomethacin, but not with diclofenac, strikingly suppressed AA-induced TxB2 generation, while treatment with diclofenac did not modify it. CONCLUSIONS: Our data show that indomethacin administered by ophthalmic eye drops has a relevant systemic antiplatelet effect. This should be taken into account in patients under concurrent therapy with antiplatelet or anticoagulant agents.
RCT Entities:
INTRODUCTION: The use of topical NSAIDs is frequent in ophthalmology to reduce the local inflammatory reaction resulting from surgical procedures. Ocular use of some drugs was previously found to lead to significant systemic absorption with possible systemic effects. NSAIDs may enhance the hemorrhagic risk of anticoagulant and antiplatelet drugs. Aim of our study was to evaluate the systemic effects of two NSAIDs given by eyedrops on platelet COX-1 and on ex vivo and in vivo platelet activation. MATERIALS AND METHODS: 20 patients planned to undergo cataract surgery were randomized to the use of an ophthalmic solution containing Diclofenac or Indomethacin. Blood was taken at enrollment (baseline) and after 3 days of therapy (1 drop, 4 times a day). Arachidonic Acid (AA)-induced light transmission aggregometry (LTA), PFA-100® C-EPI, circulating platelet P-Selectin expression by flow cytometry and serum and AA-induced TxB2 production were evaluated before and after eyedrop therapy. RESULTS: AA (0.1-0.2 mM)-induced LTA was significantly reduced after ocular indomethacin but not after diclofenac. PFA-100® C-EPI closure time was also significantly prolonged in the indomethacin group but not in the diclofenac group. Circulating platelet P-selectin expression was significantly reduced after treatment with indomethacin compared with diclofenac. Finally, treatment with eyedrop indomethacin, but not with diclofenac, strikingly suppressed AA-induced TxB2 generation, while treatment with diclofenac did not modify it. CONCLUSIONS: Our data show that indomethacin administered by ophthalmic eye drops has a relevant systemic antiplatelet effect. This should be taken into account in patients under concurrent therapy with antiplatelet or anticoagulant agents.
Authors: Delia I Fernández; Isabella Provenzale; Hilaire Y F Cheung; Jan van Groningen; Bibian M E Tullemans; Alicia Veninga; Joanne L Dunster; Saman Honarnejad; Helma van den Hurk; Marijke J E Kuijpers; Johan W M Heemskerk Journal: iScience Date: 2021-12-31