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

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 one hour 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 hours 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.

White Blood Cell Count and Major Adverse Cardiovascular Events After Percutaneous Coronary Intervention in the Contemporary Era

“…A recent study by Nidorf et al demonstrated a significant reduction on the primary composite outcome of ACS, out-of-hospital cardiac arrest, or non-cardioembolic ischemic stroke in patients with stable coronary artery disease on anti-platelet and statin therapy randomized to receive the anti-inflammatory agent colchicine versus no colchicine (35). This is likely due to the effect of colchicine on the endothelial inflammatory response, as well as the inflammatory-thrombosis axis (36)(37). Our results combined with previously published data lend support to ongoing studies targeting the inflammatory pathway across the spectrum of cardiovascular disease (NCT01594333, NCT02594111, NCT02551094).…”

Why Colchicine Should Be Considered for Secondary Prevention of Atherosclerosis: An Overview

“…35 In addition, colchicine dampens the effects of mast cells 37 and T cells 38,39 that are also pivotal in mediating the response to injury induced by (cholesterol) crystals and can impair the plateleteleukocyte interactions that are important in promoting atherothrombosis. 40 Finally, colchicine can limit the extent of inflammatory injury by promoting antiinflammatory macrophages to release IL-10, TGB-b, and other antiinflammatory cytokines that act to suppress proinflammatory signaling and promote favorable healing by dampening the growth of vascular smooth muscle cells, 41 fibrocytes, and osteophytes, which, if unchecked, may lead to excessive fibrosis, calcification, and deformity of the arterial wall. 42 Evidence Supporting the Use of Colchicine in Cardiovascular Disease…”

Guidelines for the treatment of skin and mucosal lesions in Behçet's disease: A secondary publication

“…Colchicine inhibits platelet aggregation and is effective for preventing thrombosis. 41 In seven pediatric patients with Behc ßet's disease complicated by venous thrombosis, the combination of an anticoagulant and colchicine was effective. 42 Based on these studies, colchicine is likely to be effective for superficial thrombophlebitis and is proposed as a treatment option.…”

“…Explanation : No direct effect of colchicine on superficial thrombophlebitis has been reported. Colchicine inhibits platelet aggregation and is effective for preventing thrombosis . In seven pediatric patients with Behçet's disease complicated by venous thrombosis, the combination of an anticoagulant and colchicine was effective .…”