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Arterioscler Thromb Vasc Biol. 2012 Oct;32(10):2475-83. doi: 10.1161/ATVBAHA.112.253765. Epub 2012 Jul 26.

Two types of procoagulant platelets are formed upon physiological activation and are controlled by integrin α(IIb)β(3).

Author information

1
Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russia.

Abstract

OBJECTIVE:

Phosphatidylserine (PS) externalization by platelets upon activation is a key event in hemostasis and thrombosis. It is currently believed that strong stimulation of platelets forms 2 subpopulations, only 1 of which expresses PS.

METHODS AND RESULTS:

Here, we demonstrate that physiological stimulation leads to the formation of not 1 but 2 types of PS-expressing activated platelets, with dramatically different properties. One subpopulation sustained increased calcium level after activation, whereas another returned to the basal low-calcium state. High-calcium PS-positive platelets had smaller size, high surface density of fibrin(ogen), no active integrin α(IIb)β(3), depolarized mitochondrial membranes, gradually lost cytoplasmic membrane integrity, and were poorly aggregated. In contrast, the low-calcium PS-positive platelets had normal size, retained mitochondrial membrane potential and cytoplasmic membrane integrity, and combined retention of fibrin(ogen) with active α(IIb)β(3) and high proaggregatory function. Formation of low-calcium PS-positive platelets was promoted by platelet concentration increase or shaking and was decreased by integrin α(IIb)β(3) antagonists, platelet dilution, or in platelets from kindlin-3-deficient and Glanzmann thrombasthenia patients.

CONCLUSIONS:

Identification of a novel PS-expressing platelet subpopulation with low calcium regulated by integrin α(IIb)β(3) can be important for understanding the mechanisms of PS exposure and thrombus formation.

PMID:
22837472
DOI:
10.1161/ATVBAHA.112.253765
[Indexed for MEDLINE]

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