Effect of Colchicine on Platelet-Platelet and Platelet-Leukocyte Interactions: a Pilot Study in Healthy Subjects
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Effect of Colchicine on Platelet-Platelet and Platelet-Leukocyte Interactions: a Pilot Study in Healthy Subjects Binita Shah,1,2,5 Nicole Allen,1 Bhisham Harchandani,1 Michael Pillinger,3 Stuart Katz,1 Steven P. Sedlis,1,2 Christina Echagarruga,1 Svetlana Krasnokutsky Samuels,3 Pajazit Morina,1 Prabhjot Singh,1 Liza Karotkin,1 and Jeffrey S. Berger4
Abstract—The cardioprotective mechanisms of colchicine in patients with stable ischemic heart disease remain uncertain. We tested varying concentrations of colchicine on platelet activity in vitro and a clinically relevant 1.8-mg oral loading dose administered over 1 h in 10 healthy subjects. Data are shown as median [interquartile range]. Colchicine addition in vitro decreased light transmission platelet aggregation only at supratherapeutic concentrations but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. Administration of 1.8 mg colchicine to healthy subjects had no significant effect on light transmission platelet aggregation but decreased the extent of MPA (28 % [22–57] to 22 % [19–31], p = 0.05) and NPA (19 % [16–59] to 15 % [11–30], p = 0.01), platelet surface expression of PAC-1 (370 mean fluorescence intensity (MFI) [328–555] to 333 MFI [232–407], p =0.02) and P-selectin (351 MFI [269–492] to 279 [226–364], p = 0.03), and platelet adhesion to collagen (10.2 % [2.5–32.6] to 2.0 % [0.2–9.5], p =0.09) 2 h post-administration. Thus, in clinically relevant concentrations, colchicine decreases expression of surface markers of platelet activity and inhibits leukocyte-platelet aggregation but does not inhibit homotypic platelet aggregation. KEY WORDS: colchicine; platelet aggregation; neutrophil; monocyte; tissue adhesion.
INTRODUCTION Colchicine is an anti-inflammatory agent commonly used in rheumatic diseases and pericarditis [1]. Recent data suggest potential benefit in other systemic inflammatory disease processes, including atherosclerotic heart disease [2, 3]. The cardioprotective mechanisms of colchicine have not been fully elucidated. Microtubules support the discoid shape of platelets and may play a role in platelet activation 1
Department of Medicine, Division of Cardiology, New York University School of Medicine, 227 E 30th Street, Office 835, New York, NY 10016, USA 2 Department of Medicine, Section of Cardiology, Veterans Affairs New York Harbor Health Care System, New York, NY, USA 3 Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY, USA 4 Department of Medicine, Divisions of Cardiology and Hematology, New York University School of Medicine, New York, NY, USA 5 To whom correspondence should be addressed at Department of Medicine, Division of Cardiology, New York University School of Medicine, 227 E 30th Street, Office 835, New York, NY 10016, USA. E-mail: [email protected]
[4–8]. Colchicine disrupts microtubule polymerization and dissociation and thus may inhibit platelet activation. The effect of colchicine on platelet activity is currently lim
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