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Thromb Haemost 2018; 118(04): 723-733
DOI: 10.1055/s-0038-1636915
Cellular Haemostasis and Platelets
Schattauer GmbH Stuttgart

Procoagulant Effects of Low-Level Platelet Activation and Its Inhibition by Colchicine

Caroline J. Reddel
1   ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
,
Gabrielle J. Pennings
1   ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
,
Jennifer L. Curnow
1   ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
2   Westmead Hospital, Westmead, New South Wales, Australia
,
Vivien M. Chen
1   ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
,
Leonard Kritharides
1   ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
› Author Affiliations Funding The work was supported in part by a Kick Start Grant from the Balnaves Foundation and Sydney Medical School (C.R.), and NHMRC Program grant 1037903 (to L.K.).
Further Information

Publication History

07 September 2017

17 January 2018

Publication Date:
19 March 2018 (online)

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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

Supplementary Material

 

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