Individual variations in platelet reactivity towards ADP, epinephrine, collagen and nitric oxide, and the association to arterial function in young, healthy adults

Lindkvist, Madelene; Fernberg, Ulrika; Ljungberg, Liza U.; Fälker, Knut; Fernström, Maria; Hurtig-Wennlöf, Anita; Grenegård, Magnus

doi:10.1016/j.thromres.2018.12.008

Cited by 16 publications

(8 citation statements)

References 32 publications

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“…It is worth to notice donor-dependent variation in the cytometric measurements of platelet PS exposure presented here. One possible explanation could be individual differences in platelet reactivity toward adrenaline, associated with adrenergic receptors defect or deficiencies, described previously by other authors in the context of platelet aggregation ( Tamponi et al, 1987 ; Rao et al, 1988 ; Lindkvist et al, 2019 ). Adrenaline had enhanced PS exposure on collagen-adhered platelets more strongly at an elevated shear rate which suggests that adrenaline may augment not only platelets deposition on the adhesive surface, but also platelet-related procoagulant response in a shear-dependent manner.…”

Section: Discussionmentioning

confidence: 86%

“…In 1997 ( Nakamura et al, 1997 ) demonstrated for the first time that adrenaline, at the concentration close to a clinically relevant range (20 nM), is capable of inducing platelet microaggregates formation. However, the relevance of adrenaline-platelet interaction in normal hemostasis had been unknown for a long time until a few research groups observed a moderately prolonged bleeding time and an impaired thrombi formation in α 2 -AR deficient patients ( Tamponi et al, 1987 ; Rao et al, 1988 ; Lindkvist et al, 2019 ). These observations suggested a non-redundant role of adrenaline in normal hemostatic response.…”

Section: Introductionmentioning

confidence: 99%

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Adrenaline May Contribute to Prothrombotic Condition via Augmentation of Platelet Procoagulant Response, Enhancement of Fibrin Formation, and Attenuation of Fibrinolysis

et al. 2021

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Background: Adrenaline is believed to play a role in thrombosis and hemostasis. The complex effect of its clinically relevant concentrations on thrombus formation, coagulation and fibrinolysis in human blood has never been specifically studied.Methods: Confocal microscopy was used to study thrombus formation under flow, exposure of phosphatidylserine (PS) in adhered platelets, to evaluate clots density, and to measure kinetics of fibrin formation and external fibrinolysis under flow. Flow cytometry was utilized to assess PS exposure in non-adhered platelets. Kinetics of clot formation and internal fibrinolysis was evaluated by thromboelastometry. Platelet aggregation was measured by optical aggremometry. Kinetics of clot retraction was assessed by using digital camera.Results: We found that adrenaline (1–10 nM) is able to enhance platelet activation evoked by subthreshold collagen (150 ng/ml), resulting in augmentation of platelet aggregation, thrombus formation under arterial flow conditions, platelet PS exposure, and formation of platelet-fibrin clots. The development of platelet procoagulant response evoked by adrenaline + low collagen was associated with the formation of denser platelet-fibrin clots and the decrease in rate of fibrinolysis despite whether lysis was initiated inside (internal fibrinolysis) or outside the clot (external fibrinolysis). The above phenomena were abolished by the α2-adrenergic receptor antagonist, rauwolscine. Adrenaline-collagen synergism, expressed as PS exposure, was significantly reduced by cyclooxygenase inhibitor (acetylsalicic acid), GPIIb/IIIa receptor blocker (tirofiban), and P2Y12 receptor antagonist (PSB 0739).Conclusion: Clinically relevant concentrations of adrenaline may significantly augment responses of human platelets in the presence of subthreshold concentrations of collagen, which should be considered during therapies involving adrenaline infusion. Routinely used antiplatelet drugs may reduce the prothrombotic state evoked by adrenaline-collagen synergism.

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Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Adrenaline May Contribute to Prothrombotic Condition via Augmentation of Platelet Procoagulant Response, Enhancement of Fibrin Formation, and Attenuation of Fibrinolysis

et al. 2021

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“…ADP is one of the most important mediators of hemostasis and thrombosis, and thus has been used in conventional clinical laboratory testing of platelet function [23]. In addition, because of its simple chemical constitution, we chose ADP for the development of the assay method.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, individual differences are relatively lower and we may have obtained statistical significances in ADP-induced aggregation between control platelets and the dysfunctional ones. However, recent advances in platelet studies have revealed that platelet functions, which include responses to ADP and sensitivity to aspirin, vary qualitatively and quantitatively with genetic differences among races and individuals [23,24,25,26]. To efficiently detect inherited platelet disorders or dysfunctional platelets by reducing possible quantitative variations, we performed the assay with ADP at a concentration higher than the endogenous levels and aspirin at a concentration higher than the therapeutic levels.…”

Section: Discussionmentioning

confidence: 99%

Spectrophotometric Determination of the Aggregation Activity of Platelets in Platelet-Rich Plasma for Better Quality Control

et al. 2019

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Although platelet-rich plasma (PRP) is now widely used in regenerative medicine and dentistry, contradictory clinical outcomes have often been obtained. To minimize such differences and to obtain high quality evidence from clinical studies, the PRP preparation protocol needs to be standardized. In addition, emphasis must be placed on quality control. Following our previous spectrophotometric method of platelet counting, in this study, another simple and convenient spectrophotometric method to determine platelet aggregation activity has been developed. Citrated blood samples were collected from healthy donors and used. After centrifugation twice, platelets were suspended in phosphate buffered saline (PBS) and adenosine diphosphate (ADP)-induced aggregation was determined using a spectrophotometer at 615 nm. For validation, platelets pretreated with aspirin, an antiplatelet agent, or hydrogen peroxide (H2O2), an oxidative stress-inducing agent, were also analyzed. Optimal platelet concentration, assay buffer solution, and representative time point for determination of aggregation were found to be 50–100 × 104/μL, PBS, and 3 min after stimulation, respectively. Suppressed or injured platelets showed a significantly lower aggregation response to ADP. Therefore, it suggests that this spectrophotometric method may be useful in quick chair-side evaluation of individual PRP quality.

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“…NO is a biological effector that plays an important role in vasodilation, endothelial function, and other vascular processes [7]. Previous studies have shown that NO can strongly inhibit the proliferation of SMCs [8][9][10][11][12] and resist platelet aggregation [13] and leukocyte adhesion, while improving endothelial cell function at low doses [14]. Therefore, NO can be used as a selective antistenosis drug.…”

Section: Introductionmentioning

confidence: 99%

Electrospun fiber membrane with asymmetric NO release for the differential regulation of cell growth

et al. 2021

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The high incidence of cardiovascular disease has led to significant demand for synthetic vascular grafts in clinical applications. Anti-proliferation drugs are usually loaded into devices to achieve desirable anti-thrombosis effects after implantation. However, the non-selectiveness of these conventional drugs can lead to the failure of blood vessel reconstruction, leading to potential complications in the long term. To address this issue, an asymmetric membrane was constructed through electrospinning techniques. The bilayer membrane loaded and effectively released nitric oxide (NO), as hoped, from only one side. Due to the short diffusion distance of NO, it exerted negligible effects on the other side of the membrane, thus allowing selective regulation of different cells on both sides. The released NO boosted the growth of endothelial cells (ECs) over smooth muscle cells (SMCs)-while on the side where NO was absent, SMCs grew into multilayers. The overall structure resembled a native blood vessel, with confluent ECs as the inner layer and layers of SMCs to support it. In addition, the membrane preserved the normal function of ECs, and at the same time did not exacerbate inflammatory responses. By preparing this material type that regulates cell behavior differentially, we describe a new method for its application in the cardiovascular field such as for artificial blood vessels.

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Individual variations in platelet reactivity towards ADP, epinephrine, collagen and nitric oxide, and the association to arterial function in young, healthy adults

Cited by 16 publications

References 32 publications

Adrenaline May Contribute to Prothrombotic Condition via Augmentation of Platelet Procoagulant Response, Enhancement of Fibrin Formation, and Attenuation of Fibrinolysis

Adrenaline May Contribute to Prothrombotic Condition via Augmentation of Platelet Procoagulant Response, Enhancement of Fibrin Formation, and Attenuation of Fibrinolysis

Spectrophotometric Determination of the Aggregation Activity of Platelets in Platelet-Rich Plasma for Better Quality Control

Electrospun fiber membrane with asymmetric NO release for the differential regulation of cell growth

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