Effect of Colchicine on Platelet-Platelet and Platelet-Leukocyte Interactions: a Pilot Study in Healthy Subjects

• Published in: Inflammation Vol. 39; no. 1; pp. 182 - 189
• Main Authors: Shah, Binita, Allen, Nicole, Harchandani, Bhisham, Pillinger, Michael, Katz, Stuart, Sedlis, Steven P., Echagarruga, Christina, Samuels, Svetlana Krasnokutsky, Morina, Pajazit, Singh, Prabhjot, Karotkin, Liza, Berger, Jeffrey S.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2016; Springer Nature B.V
• Subjects: Adult; Biomedical and Life Sciences; Biomedicine; Blood Platelets - drug effects; Blood Platelets - metabolism; Cardiotonic Agents - pharmacology; Cell Adhesion - drug effects; Colchicine - pharmacology; Female; Healthy Volunteers; Humans; Immunology; Inflammation - drug therapy; Internal Medicine; Male; Monocytes - drug effects; Monocytes - metabolism; Myocardial Ischemia - drug therapy; Neutrophils - drug effects; Neutrophils - metabolism; Pathology; Pharmacology/Toxicology; Pilot Projects; Platelet Activation - drug effects; Platelet Aggregation - drug effects; Platelet Aggregation - physiology; Prospective Studies; Rheumatology; Young Adult; tissue adhesion; colchicine; monocyte; neutrophil; platelet aggregation
• ISSN: 0360-3997; 1573-2576; 1573-2576
• DOI: 10.1007/s10753-015-0237-7

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.