Two Types of Procoagulant Platelets Are Formed Upon Physiological Activation and Are Controlled by Integrin αIIbβ3
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 αIIbβ3, 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 αIIbβ3 and high proaggregatory function. Formation of low-calcium PS-positive platelets was promoted by platelet concentration increase or shaking and was decreased by integrin αIIbβ3 antagonists, platelet dilution, or in platelets from kindlin-3–deficient and Glanzmann thrombasthenia patients.
Conclusion—Identification of a novel PS-expressing platelet subpopulation with low calcium regulated by integrin αIIbβ3 can be important for understanding the mechanisms of PS exposure and thrombus formation.
- Received February 16, 2012.
- Accepted July 4, 2012.
- © 2012 American Heart Association, Inc.