Correlations among different platelet aggregation pathways in a group of healthy volunteers

Figures & data

Figure 1. Platelet activation pathways of the different platelet triggers and antiplatelet compounds used. Tested inducers are depicted as yellow ellipses while tested antiplatelet drugs as red ellipses. Abbreviations: AA: arachidonic acid; ADP: adenosine diphosphate; ASA: acetylsalicylic acid; COX-1: cyclooxygenase-1; cPLA2: cytosolic phospholipase A₂; DTS: dense tubular system; Gi: G protein α subunit i; GP Ib: glycoprotein Ib; GP VI: glycoprotein VI; Gq: G protein α subunit q; IP₃: inositol triphosphate, P2RY₁, P2RY₁₂: two receptors for ADP, PAF: platelet activating factor; PAFR: PAF receptor; PAR1: protease activated receptor 1; PIP₂: phosphatidylinositol 4,5-biphosphate; PKC: protein kinase C; TP: thromboxane receptor, TRAP: thrombin receptor-activating peptide; TXA₂: thromboxane A₂; α2β1: integrin α₂β₁.

Figure 2. The strongest associations between platelet aggregatory responses to inducers. (a): arachidonic acid (200 μM) and collagen (1 μg/mL), (d): arachidonic acid (200 μM) and U-46619 (80 nM), (c): arachidonic acid (200 μM) and TRAP (10 μM), (b): ADP (5 μM) and ristocetin (400 μM), (e): collagen (1 μg/mL) and acetylsalicylic acid (70 μM) + collagen (1 μg/mL), (f): ticagrelor 500 nM + ADP (5 μM) and vorapaxar (5 μM) and TRAP (10 μM). AUC: area under the curve measured by impedance aggregometry.

Table I. Relationships between responses to different aggregation inducers.

	AA 200	Collagen 0.16	Collagen 1	ADP	Ristocetin	TRAP	U-46619	PAF
AA60	0.47***	0.44**	0.45**	0.50***	0.46***	0.45**	0.55***	0.30*
	AA200	0.30*	0.85***	0.70***	0.70***	0.73***	0.75***	0.66***
		collagen 0.16	0.44**	0.43**	0.43**	0.32*	0.33*	0.39**
			collagen 1	0.59***	0.61***	0.72***	0.66***	0.55***
				ADP	0.81***	0.65***	0.56***	0.57***
					ristocetin	0.65***	0.61***	0.70***
						TRAP	0.53***	0.65***
							U-44619	0.66***

The data show the Pearson correlation coefficients of area under the curve for impedance aggregation measurements. *p < .05, **p < .01, ***p < .001. AA 60 – arachidonic acid 60 μM, AA 200 – arachidonic acid 200 μM, collagen 0.16 – collagen 0.16 μg/mL, collagen 1 - collagen 1 μg/mL, ADP −5 μM, ristocetin − 400 μM, TRAP (thrombin receptor activation protein 6) − 10 μM, U-44619 – 80 nM, PAF (platelet activating factor 16) − 20 nM. Bold values represent the highest correlations found (>0.7).

Table II. Relationships between responses to different platelet aggregation inhibitors and platelet aggregation inducers.

	AA 200 + ASA 30	AA 200 + ASA 70	collagen 1 + ASA 70	ticagrelor + ADP	vorapaxar 1 + TRAP	vorapaxar 5 + TRAP
AA 60	0.62***	0.45**	0.40**	0.35*	n.s.	0.40*
AA200	0.61***	n.s.	0.57***	0.56***	0.30*	0.37*
collagen 0.16	0.40**	0.63***	0.76***	n.s.	0.53***	0.59***
collagen 1	0.46***	n.s.	0.70***	0.59***	0.36**	0.37*
ADP	0.57***	n.s.	0.52***	0.59***	0.35*	0.46**
ristocetin	0.49***	0.32*	0.52***	0.47***	n.s.	0.48**
TRAP	0.49***	n.s.	0.55***	0.3*	0.47***	n.s.
U-44619	0.60***	n.s.	0.34*	0.43**	n.s.	0.37*
PAF	0.57***	0.36**	0.36**	n.s.	n.s.	n.s.
	AA 200 + ASA 30	0.53***	0.38**	0.43**	n.s.	0.42**
		AA 200 + ASA 70	0.40***	n.s.	n.s.	0.37*
			collagen 1 + ASA 70	0.43**	0.44**	0.34*
				ticagrelor + ADP	n.s.	0.71***

The data show the Pearson correlation coefficients of area under the curve for impedance aggregation measurements. *p < .05, **p < .01, *** p < .001. n.s.: non-significance. AA 60 – arachidonic acid 60 μM, AA 200 – arachidonic acid 200 μM, collagen 0.16 – collagen 0.16 μg/mL, collagen 1 - collagen 1 μg/mL, ADP − 5 μM, ristocetin −400 μM, TRAP (thrombin receptor activating protein 6) − 10 μM, U-44619 - 80 nM, PAF (platelet activating factor 16) − 20 nM, ASA 30 + AA 200 – acetylsalicylic acid 30 μM + arachidonic acid 200 μM, ASA 70 + AA 200 – acetylsalicylic acid 70 μM + arachidonic acid 200 μM, ASA 70 + collagen 1 - acetylsalicylic acid 70 μM + collagen 1 μg/mL, ticagrelor + ADP – ticagrelor 500 nM + ADP 5 μM, vorapaxar 1 + TRAP – vorapaxar 1 μM + TRAP 10 μM, vorapaxar 5 + TRAP – vorapaxar 5 μM + TRAP 10 μM. Bold values represent the highest correlations found (>0.7).