Enhanced shear‐induced platelet aggregation due to low‐temperature storage

Montgomery, Robbie K.; Reddoch, Kristin M.; Evani, Shankar J.; Andrew, P.; Ramasubramanian, Anand K.

doi:10.1111/j.1537-2995.2012.03917.x

Cited by 66 publications

(93 citation statements)

References 34 publications

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“…This model is also consistent with previous studies that activation of GPIb-IX by VWF or anti-GPIbα antibodies leads to increased [Ca 2+ ] i , PS exposure, and platelet desialylation 11, 15 , and that GPIb-IX is associated with the procoagulant activity of platelets 25, 26 . Moreover, refrigeration-induced VWF binding may also enhance the GPIbα-dependent platelet activation under high shear 26 . Here we report the requirement of shear stress for refrigeration-induced platelet signaling (Fig.…”

Section: Discussionsupporting

confidence: 93%

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Refrigeration-Induced Binding of von Willebrand Factor Facilitates Fast Clearance of Refrigerated Platelets

Chen

Druzak

Wang

et al. 2017

ATVB

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Objective Apheresis platelets for transfusion treatment are currently stored at room temperature because after refrigeration platelets are rapidly cleared upon transfusion. In this study, the role of von Willebrand factor (VWF) in the clearance of refrigerated platelets is addressed. Approach and Results Human and murine platelets were refrigerated in gas-permeable bags at 4°C for 24 hours. VWF binding, platelet signaling events, and platelet post-transfusion recovery and survival were measured. After refrigeration the binding of plasma VWF to platelets was drastically increased, confirming earlier studies. The binding was blocked by peptide OS1 that bound specifically to platelet glycoprotein (GP)Ibα and was absent in VWF−/− plasma. Although surface expression of GPIbα was reduced after refrigeration, refrigeration-induced VWF binding under physiological shear induced unfolding of the GPIbα mechanosensory domain on the platelet, as evidenced by increased exposure of a linear epitope therein. Refrigeration and shear treatment also induced small elevation of intracellular Ca2+, phosphatidylserine exposure and desialylation of platelets, which were absent in VWF−/− platelets or inhibited by OS1. Furthermore, refrigerated VWF−/− platelets displayed increased post-transfusion recovery and survival than wild-type ones. Similarly, adding OS1 to transgenic murine platelets expressing only human GPIbα during refrigeration improved their post-transfusion recovery and survival. Conclusions Refrigeration-induced binding of VWF to platelets facilitates their rapid clearance by inducing GPIbα-mediated signaling. Our results suggest that inhibition of the VWF-GPIbα interaction may be a potential strategy to enable refrigeration of platelets for transfusion treatment.

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Section: Discussionsupporting

confidence: 93%

“…Here we report the requirement of shear stress for refrigeration-induced platelet signaling (Fig. 2), which fits the observation that GPIb-IX is a mechanoreceptor and requires shear for its signaling function 26–28 . In our experiments a shear stress of 10 dyn/cm 2 was utilized.…”

Section: Discussionsupporting

confidence: 88%

Refrigeration-Induced Binding of von Willebrand Factor Facilitates Fast Clearance of Refrigerated Platelets

Chen

Druzak

Wang

et al. 2017

ATVB

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“…Indeed, mitochondrial generated ATP provides the major source of energy used for maintaining platelet cellular integrity and function both in vivo and during storage. (9, 15, 18, 19) In this study, we investigated the relationship between mitochondrial function and the capacity for platelet activation as a function of storage time. Our research demonstrates that stored platelets experience a dramatic decrease in mitochondrial respiration in conjunction with increased ROS production, enhanced apoptosis, and decreased functional capacity.…”

Section: Discussionmentioning

confidence: 99%

“…(5, 7, 9,19) In our study, we tested platelet function in stored units by using a strong thrombin receptor stimulator (SFLLRN) to induce platelet activation. By the 3 rd day of storage, only ~2 % of platelets were able to respond appropriately.…”

Section: Discussionmentioning

confidence: 99%

“…Given the risk of premature activation, platelets intended for transfusion must be stored at room temperature, in gas permeable bags and with constant agitation. (9) Despite these current practices, over time stored platelets develop a “platelet storage lesion” that is characterized by a gradual decline in activation, aggregation and degranulation – all processes that are highly energetic and necessary for adequate hemostatic function. (10,11) Moreover, given that storage time has been shown to increase reactive oxygen species production as well as enhance apoptosis,(12,13) we hypothesized that increased platelet storage time would directly correlate with mitochondrial dysfunction and the subsequent development of impaired platelet activation.…”

Section: Introductionmentioning

confidence: 99%

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Increased platelet storage time is associated with mitochondrial dysfunction and impaired platelet function

Villarroel

Figueredo

Guan

et al. 2013

Journal of Surgical Research

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Background Hemorrhagic shock is a leading cause of death following severe trauma and platelet transfusions are frequently necessary to achieve hemostasis. Platelets, however, require special storage conditions and storage time has been associated with loss of platelet quality. We hypothesized that standard storage conditions have a deleterious effect on platelet mitochondrial function and platelet activation. Materials and methods Platelet donations were collected from healthy donors (n=5), and stored in gas permeable collection bags according to American Association of Blood Bank recommendations. Platelet units were sampled from day of collection (day 0) until day 7. High resolution respirometry was used to assess baseline mitochondrial respiration, maximal oxygen utilization, and individual mitochondrial complex-dependent respiration. FACS was performed to analyze mitochondrial content, mitochondrial reactive oxygen species (ROS), the expression of P-selectin (both before and after challenge with thrombin receptor activating peptide (SFLLRN)), and apoptosis. Data was analyzed using ANOVA and Pearson’s correlation (p<0.05 significant). Results Mitochondrial respiration decreased significantly in platelets stored longer than 2 days (p<0.05). Platelets also demonstrated a persistent decrease in response to stimulation with SFLLRN by the 3rd day of storage (p<0.05) as well as an increase in mitochondrial ROS and apoptosis (p<0.05). Mitochondrial respiration significantly correlated with platelet capacity to activate (r=0.8, p<0.05). Conclusion Platelet mitochondrial respiratory function and activation response decrease significantly in platelets stored for 3 or more days. Because platelet transfusions almost universally occur between the 3rd and 5th day of storage, our findings may have significant clinical importance and warrant further in vivo analysis.

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Determination of free serotonin and its metabolite 5‐HIAA in blood human samples with consideration to pre‐analytical factors

Yubero-Lahoz

Rodríguez

Faura

et al. 2014

Biomedical Chromatography

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Significant differences have been reported over the years in measuring physiological levels of free circulating serotonin (f5-HT) in platelet-poor plasma (PPP). This work shows that there are crucial pre-analytical factors in sample manipulation that can provoke an artifactual release of 5-HT from platelets, and that, even when the sample is accurately processed to obtain PPP, f5-HT levels are approximately 2.8 times higher than those of f5-HT in blood. An alternative methodology consisting of ex vivo blood microdialysis coupled to high-performance liquid chromatography-electrochemical detection is proposed and validated. It is considered the most accurate technique to measure physiological circulating f5-HT and its metabolite 5-hydroxyindoleacetic acid (f5-HIAA), owing to its sensitivity (limits of quantification of 0.08 ng/mL) and reliability since there is no sample manipulation. The f5-HT and f5-HIAA levels in blood and in PPP were studied in control subjects, hypertensive and end-stage renal disease patients, who have a deregulated serotonergic system. This work reveals that blood is the best matrix to determine f5-HT concentrations, and the clinical relevance of the accuracy of f5-HT determination is discussed.

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Enhanced shear‐induced platelet aggregation due to low‐temperature storage

Cited by 66 publications

References 34 publications

Refrigeration-Induced Binding of von Willebrand Factor Facilitates Fast Clearance of Refrigerated Platelets

Refrigeration-Induced Binding of von Willebrand Factor Facilitates Fast Clearance of Refrigerated Platelets

Increased platelet storage time is associated with mitochondrial dysfunction and impaired platelet function

Determination of free serotonin and its metabolite 5‐HIAA in blood human samples with consideration to pre‐analytical factors

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