Table 1.

Platelet response to stress.

Platelet Response to Stress	Major Biological Molecules Involved	Mechanisms/Consequences
Apoptosis	Death domains receptors Caspase activation cascades	Associated with platelet concentrate storage lesion [37] Cytoplasmic condensation [38] PS exposure [38] CD62P expression on the platelet plasma membrane [38] Altered mitochondrial signaling pathways, inner mitochondrial membrane disruption, and cytochrome c leaking [39]
	PKA	PKA activity correlated with platelet survival [40] Sequestration of prosurvival protein Bcl-xL in mitochondria upon PKA inhibition [41] Protection from apoptosis upon PKA activation [41]
	Siglec-7	Depolarization of the mitochondrial inner membrane [42] Overexpression of proapoptotic Bax and Bak proteins [42] Decreased expression of anti-apoptotic Bcl-2 proteins [42] Abnormal PS exposure to the platelet membrane [42] Formation of platelet microparticles [42]
	TRAF-2/5 FADD DEDAF	No activation of caspase 3/7 or PS exposure upon triggering of extrinsic apoptosis pathways [46]
	PAR-1 GPIIb/IIIa GPIbα	Platelet activation [48]
	TLR2	Caspase-3 activation [53] Bcl-xL degradation [54]
Necrosis	CypD	Formation of mitochondrial permeability transition pores in the inner mitochondria membrane [58,59] Contribution to thrombosis by displaying a procoagulant surface [60] Platelet association to neutrophils and accumulation in the brain [61] and in the lungs [57]
	DAMPs	Recruitment of proinflammatory phagocytes upon DAMP release by necrotic platelets [55]
	RIPK3	Thrombus formation and stability [67]
Autophagy	PI3k/Akt/mTOR pathway LC3-II ATG7 VPS34	Platelet adhesion and aggregation [72] Platelet activation related to autophagic flux [73] ATG7-dependent platelet aggregation, but ATG7-independent platelet count, fibrinogen binding and spreading [73] VPS34-dependent thrombus formation [74] Increased phenotypic platelet activation and decreased platelet aggregation rate [77] Negatively correlated with clinical platelet transfusion efficacy [77]

ATG: autophagy-related protein, Bak: Bcl-2 homologous antagonist killer, Bax: Bcl-2-associated X, Bcl-2: B-cell lymphoma 2, Bcl-xL: B-cell lymphoma extra-large, CypD: Cyclophilin D, DAMP: damage-associated molecular pattern, DEDAF: death effector domain-associated factor, FADD: Fas-associated protein with death domain, GP: glycoprotein, LC3: microtubule-associated proteins 1A/1B light chain 3, PAR-1: protease-activated receptor-1, PKA: protein kinase A, PS: phosphatidylserines, RIPK3: receptor-interacting protein kinase 3, Siglec: sialic acid-binding immunoglobulin-type lectin, TLR: toll-like receptor, TRAF: tumor necrosis factor (TNF)-associated factor, VPS: vacuolar protein sorting.