Abstract
Platelets play an important role in diseases such as cardiovascular disease and cancer,
especially through their release of extracellular vesicles (EVs) and role in thrombosis.
The effects of the anti-inflammatory drug colchicine on platelets are not well understood.
We investigated the effect of colchicine on the release of pro-coagulant EVs from
platelets under low-level activation. Citrated platelet-rich plasma (PRP) from healthy
donors was incubated with 2 mM colchicine or vehicle at 37°C for 30 minutes with gentle
rotation. The incubation conditions caused mild platelet activation (expression of
CD62P and increased surface lactadherin binding) and release of EVs expressing phosphatidylserine
(PS, measured by binding of lactadherin), CD61 and CD62P, both of which were attenuated
by colchicine. The incubation conditions shortened the delay to fibrin generation
and this correlated with elevated levels of PS+/CD61+ EVs. Removal of EVs from plasma
abrogated clot formation in the overall haemostatic potential (OHP) assay. Colchicine
decreased levels of both PS+/CD61+ and CD62P+ EVs and abrogated the shortened delay
to fibrin generation achieved by platelet activation. Similar results were observed
after incubation of PRP with 200 µM vinblastine, suggesting a microtubular effect.
An alternative method of platelet activation using platelet agonists 20 µM ADP or
10 µM epinephrine also increased CD62P+ EV levels, and this too was attenuated by
prior incubation with colchicine. Our novel findings demonstrate procoagulant effects
of low-level platelet activation and EV formation which are inhibited by colchicine.
Keywords
platelet physiology - microparticles - haemostasis
