Thrombin receptor levels in platelet concentrates during storage and their impact on platelet functionality

Schlagenhauf, Axel; Kozma, Noemi; Leschnik, B.; Muntean, W.

doi:10.1111/j.1537-2995.2011.03475.x

Cited by 15 publications

(16 citation statements)

References 25 publications

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“…Thus, it appears that the activation state attained by platelets due to 4°C storage may be different from activation states associated with either RT storage or prior activation with chemical stimuli. The similar decline in aggregation response to TRAP activation for both storage temperatures may be due to a loss of thrombin receptors (53). …”

Section: Discussionmentioning

confidence: 99%

Hemostatic Function of Apheresis Platelets Stored at 4°C and 22°C

Reddoch

Pidcoke

Montgomery

et al. 2014

Shock

227

326

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Introduction Platelet refrigeration decreases the risk of bacterial contamination and may preserve function better than standard-of-care room temperature storage. Benefits could include lower transfusion-related complications, decreased costs, improved hemostasis in acutely bleeding patients, and extended shelf-life. In this study, we compared the effects of 22°C and 4°C storage on the functional and activation status of apheresis platelets (APs). Methods APs (n = 5 per group) were stored for 5 days at 22°C with agitation (RT) versus at 4°C with agitation (4C+AG) and without (4C). Measurements included platelet counts, mean platelet volume, blood gas analytes, aggregation response, thromboelastography, TxB2 and sCD40L release, activation markers and microparticle formation. Results Sample pH levels were within acceptable limits for storage products (pH 6.2-7.4). Platelet glucose metabolism (P < 0.05), aggregation response (ADP: RT 0; 4C+AG 5.0 ± 0.8; 4C 5.6 ± 0.9; P < 0.05), and clot strength (MA: RT 58 ± 2; 4C+AG 63 ± 2; 4C 67 ± 2; P < 0.05) were better preserved at 4°C compared to RT storage. Refrigerated samples were more activated compared to RT (P < 0.05), although TxB2 (P < 0.05) and sCD40L release (P < 0.05) were higher at RT. Agitation did not improve the quality of 4°C-stored samples. Conclusion AP stored at 4°C maintain more viable metabolic characteristics, are hemostatically more effective, and release fewer pro-inflammatory mediators than AP stored at RT over 5 days. Given the superior bacteriologic safety of refrigerated products, these data suggest that cold-stored platelets may improve outcomes for acutely bleeding patients.

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Section: Discussionmentioning

confidence: 99%

Hemostatic Function of Apheresis Platelets Stored at 4°C and 22°C

Reddoch

Pidcoke

Montgomery

et al. 2014

Shock

227

326

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“…There was no significant difference in aggregation between DEA/NOtreated and untreated PLTs after activation with TRAP-6 and collagen (Figs. [3][4][5], despite strong VASP phosphorylation induced by 5 nmol/L DEA/NO in fresh PLTs from WB and APCs on Day 0 ( Fig. 1).…”

Section: Discussionmentioning

confidence: 90%

“…Furthermore, both the number of high‐affinity thrombin receptors and thrombin‐induced fibrinogen binding are reduced throughout storage of APCs . In addition, a progressive functional impairment of stored PLTs was described, associated with diminished adhesive capacities or reduced agonist‐induced PLT aggregation 5‐7…”

mentioning

confidence: 99%

“…2 Furthermore, both the number of high-affinity thrombin receptors and thrombin-induced fibrinogen binding are reduced throughout storage of APCs. 3 In addition, a progressive functional impairment of stored PLTs was described, associated with diminished adhesive capacities 4 or reduced agonist-induced PLT aggregation. [5][6][7] Normal PLT function is also conditioned by the inhibitory regulation of activating signal cascades mediated by cyclic adenosine monophosphate (cAMP)-and cyclic guanosine monophosphate (cGMP)-dependent phosphorylation of target proteins.…”

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confidence: 99%

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Increasing susceptibility of nitric oxide–mediated inhibitory platelet signaling during storage of apheresis‐derived platelet concentrates

et al. 2014

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“…Thrombin is generally considered to be a potent inducer of platelet aggregation and usually induces high irreversible aggregation,21,22 so reduction of platelet reactivity in response to this agonist was a surprise. The thrombin effect on platelets is realized through PAR-1 and PAR-4, which are the most numerous types of receptors on platelets (1,500–2,000 per platelet), and also through glycoprotein (GP) Ib 13…”

Section: Discussionmentioning

confidence: 99%

Platelet aggregation measurement for assessment of hemostasis failure mechanisms in patients with gastroduodenal ulcer bleeding

Barinov¹,

Sulaieva²,

Lyakch³

et al. 2013

CEG

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BackgroundThe purpose of this study was to identify factors associated with the risk of unsustainable hemostasis in patients with gastric and duodenal ulcer bleeding by in vitro assessment of platelet reactivity using artificial neural networks.MethodsPatients with gastroduodenal ulcers complicated by bleeding were studied. Platelet aggregation was measured using aggregometry with adenosine diphosphate 5 μM, epinephrine 2.5 μM, 5-hydroxytryptophan 10 μM, collagen 1 μM, and thrombin 0.06 NIH Unit/mL as agonists. Multiple logistic regression was used to evaluate the independent relationship between demographic, clinical, endoscopic, and laboratory data and in vitro assessment of platelet reactivity and local parameters of hemostasis in patients with ulcer bleeding.ResultsAnalysis of platelet aggregation in patients with gastroduodenal ulcer bleeding allowed the variability of platelet response to different agonists used in effective concentration which induces 50% platelet aggregation (EC50) to be established. The relationship between platelet aggregation and the spatial-temporal characteristics of ulcers complicated by bleeding was demonstrated. Adrenoreactivity of platelets was associated with time elapsed since the start of ulcer bleeding and degree of hemorrhage. The lowest platelet response to collagen and thrombin was detected in patients with active bleeding (P < 0.001) and unsustainable recent bleeding (P < 0.01). Decreased adenosine diphosphate-induced platelet aggregation in patients with ulcer bleeding was correlated with the platelet response to thrombin (r = 0.714, P < 0.001) and collagen (r = 0.584, P < 0.01).ConclusionEstimation of platelet reactivity in vitro indicates the key mechanisms of failure of hemostasis in patients with ulcer bleeding. In addition to gender, an important determinant of unsustainable hemostasis was a decreased platelet response to thrombin and adenosine diphosphate.

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Thrombin receptor levels in platelet concentrates during storage and their impact on platelet functionality

Abstract: Decreasing levels of PARs in PLT concentrates after 5 days of storage influenced PAR4-mediated, but not PAR1-mediated, aggregation. Thrombin generation with senescent PLTs was increased, which may be attributed to other mechanisms promoting increased phosphatidylserine exposure.

Cited by 15 publications

References 25 publications

Hemostatic Function of Apheresis Platelets Stored at 4°C and 22°C

Hemostatic Function of Apheresis Platelets Stored at 4°C and 22°C

Increasing susceptibility of nitric oxide–mediated inhibitory platelet signaling during storage of apheresis‐derived platelet concentrates

Platelet aggregation measurement for assessment of hemostasis failure mechanisms in patients with gastroduodenal ulcer bleeding

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