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J Thromb Haemost. 2010 Nov;8(11):2554-62. doi: 10.1111/j.1538-7836.2010.04043.x.

Platelet apoptosis by cold-induced glycoprotein Ibα clustering.

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Department of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands.



Cold-storage of platelets followed by rewarming induces changes in Glycoprotein (GP) Ibα-distribution indicative of receptor clustering and initiates thromboxane A(2) -formation. GPIbα is associated with 14-3-3 proteins, which contribute to GPIbα-signaling and in nucleated cells take part in apoptosis regulation.


We investigated whether GPIbα-clustering induces platelet apoptosis through 14-3-3 proteins during cold (4 h 0 °C)-rewarming (1 h 37 °C).


During cold-rewarming, 14-3-3 proteins associate with GPIbα and dissociate from Bad inducing Bad-dephosphorylation and activation. This initiates pro-apoptosis changes in Bax/Bcl-x(L) and Bax-translocation to the mitochondria, inducing cytochrome c release. The result is activation of caspase-9, which triggers phosphatidylserine exposure and platelet phagocytosis by macrophages. Responses are prevented by N-acetyl-D-glucosamine (GN), which blocks GPIbα-clustering, and by O-sialoglycoprotein endopeptidase, which removes extracellular GPIbα.


Cold-rewarming triggers apoptosis through a GN-sensitive GPIbα-change indicative of receptor clustering. Attempts to improve platelet transfusion by cold-storage should focus on prevention of the GPIbα-change.

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