@article{Millar2018,
title = {Routine Screening Method for Microparticles in Platelet Transfusions},
author = {Millar, D., Murphy, L., Labrie, A., Maurer-Spurej, E.},
url = {https://www.jove.com/video/56893/routine-screening-method-for-microparticles-in-platelet-transfusions},
doi = {10.3791/56893},
year = {2018},
date = {2018-01-31},
journal = {Journal of Visual Experiments},
number = {131},
abstract = {Platelet inventory management based on screening microparticle content in platelet concentrates is a new quality improvement initiative for hospital blood banks. Cells fragment off microparticles (MP) when they are stressed. Blood and blood components may contain cellular fragments from a variety of cells, most notably from activated platelets. When performing their roles as innate immune cells and major players in coagulation and hemostasis, platelets change shape and generate microparticles. With dynamic light scattering (DLS)-based microparticle detection, it is possible to differentiate activated (high microparticle) from non-activated (low microparticle) platelets in transfusions, and optimize the use of this scarce blood product. Previous research suggests that providing non-activated platelets for prophylactic use in hematology-oncology patients could reduce their risk of becoming refractory and improve patient care. The goal of this screening method is to routinely differentiate activated from non-activated platelets. The method described here outlines the steps to be performed for routine platelet inventory management in a hospital blood bank: obtaining a sample from a platelet transfusion, loading the sample into the capillary for DLS measurement, performing the DLS test to identify microparticles, and using the reported microparticle content to identify activated platelets.

INTRODUCTION},
keywords = {Microparticle, Platelet Activation Status},
pubstate = {published},
tppubtype = {article}
}

@article{Kanzler2017,
title = {Microparticle detection to guide platelet management for the reduction of platelet refractoriness in children – A study proposal},
author = {Kanzler, Peter et al.},
url = {http://www.trasci.com/article/S1473-0502(16)30202-6/fulltext},
doi = {10.1016/j.transci.2016.12.016},
year = {2017},
date = {2017-02-01},
journal = {Transfusion and Apheresis Science},
volume = {56},
number = {1},
pages = {39-44},
abstract = {Microparticles have been shown to shed from a variety of viable cells as a consequence of inflammatory processes, activation or physical stress. Seventy to 90% of circulating microparticles are thought to be platelet-derived. The content of microparticles in blood collected from normal blood donors is highly variable and transfers into the final blood component. Elevated microparticle content (MPC) in donor blood might indicate an asymptomatic clinical condition of the donor which might affect the transfusion recipient, particularly pediatric patients. ThromboLUX is a new technology designed to routinely test biological samples for microparticle content. We compared MPC in platelet-rich plasma (PRP) of apheresis donors and the corresponding INTERCEPT-treated apheresis products (N = 24). The MPCs in donor and product samples were correlated (r = 0.74, P < 0.001). Microparticles were significantly reduced after plasma replacement and INTERCEPT treatment. These findings are supported by phase contrast microscopy. Platelet transfusions given to patients with fever or systemic inflammation are less efficacious. In addition, transfusing heterogeneous platelets – concentrates with high MPC and activated platelets – to patients whose immune systems are activated might tip them over a threshold and cause platelet refractoriness. Restricting prophylactic platelet transfusions to homogeneous products – concentrates with resting platelets and therefore low MPC – may reduce the risk of refractoriness in cancer patients, especially children with immature immunity. To test this hypothesis we introduce an evaluation protocol for platelet management, i.e., keeping a split inventory of homogeneous and heterogeneous platelets, and using only homogeneous platelets for prophylaxis as a strategy to reduce refractoriness.},
keywords = {Microparticle, Platelet Refractoriness},
pubstate = {published},
tppubtype = {article}
}

@article{Maurer-Spurej2016b,
title = {Could Microparticles Be the Universal Quality Indicator for Platelet Viability and Function?},
author = {Elisabeth Maurer-Spurej and Kate Chipperfield},
editor = {Denese Marks},
url = {https://www.hindawi.com/journals/jbt/2016/6140239/},
doi = {10.1155/2016/6140239},
year = {2016},
date = {2016-11-06},
journal = {Journal of Blood Transfusion},
volume = {2016},
number = {Article ID 6140239},
pages = {11},
abstract = {High quality means good fitness for the intended use. Research activity regarding quality measures for platelet transfusions has focused on platelet storage and platelet storage lesion. Thus, platelet quality is judged from the manufacturer’s point of view and regulated to ensure consistency and stability of the manufacturing process. Assuming that fresh product is always superior to aged product, maintaining in vitro characteristics should preserve high quality. However, despite the highest in vitro quality standards, platelets often fail in vivo. This suggests we may need different quality measures to predict platelet performance after transfusion. Adding to this complexity, platelets are used clinically for very different purposes: platelets need to circulate when given as prophylaxis to cancer patients and to stop bleeding when given to surgery or trauma patients. In addition, the emerging application of platelet-rich plasma injections exploits the immunological functions of platelets. Requirements for quality of platelets intended to prevent bleeding, stop bleeding, or promote wound healing are potentially very different. Can a single measurable characteristic describe platelet quality for all uses? Here we present microparticle measurement in platelet samples, and its potential to become the universal quality characteristic for platelet production, storage, viability, function, and compatibility.},
keywords = {Microparticle, Platelet Activation Status},
pubstate = {published},
tppubtype = {article}
}

@article{Maurer-Spurej2016,
title = {Microparticle content of platelet concentrates is predicted by donor microparticles and is altered by production methods and stress},
author = {Maurer-Spurej, Elisabeth et al.},
url = {http://www.trasci.com/article/S1473-0502(16)30078-7/fulltext},
doi = {10.1016/j.transci.2016.07.010},
year = {2016},
date = {2016-08-01},
journal = {Transfusion and Apheresis Science},
volume = {55},
number = {1},
pages = {35-43},
abstract = {In circulation, shedding of microparticles from a variety of viable cells can be triggered by pathological activation of inflammatory processes, by activation of coagulation or complement systems, or by physical stress. Elevated microparticle content (MPC) in donor blood might therefore indicate a clinical condition of the donor which, upon transfusion, might affect the recipient. In blood products, elevated MPC might also represent product stress. Surprisingly, the MPC in blood collected from normal blood donors is highly variable, which raises the question whether donor microparticles are present in-vivo and transfer into the final blood component, and how production methods and post-production processing might affect the MPC. We measured MPC using ThromboLUX in (a) platelet-rich plasma (PRP) of 54 apheresis donors and the corresponding apheresis products, (b) 651 apheresis and 646 pooled platelet concentrates (PCs) with plasma and 414 apheresis PCs in platelet additive solution (PAS), and (c) apheresis PCs before and after transportation, gamma irradiation, and pathogen inactivation (N = 8, 7, and 12 respectively). ThromboLUX-measured MPC in donor PRP and their corresponding apheresis PC samples were highly correlated (r = 0.82, P = .001). The average MPC in pooled PC was slightly lower than that in apheresis PC and substantially lower in apheresis PC stored with PAS rather than plasma. Mirasol Pathogen Reduction treatment significantly increased MPC with age. Thus, MPC measured in donor samples might be a useful predictor of product stability, especially if post-production processes are necessary.},
keywords = {Donor, Microparticle},
pubstate = {published},
tppubtype = {article}
}

@article{Labrie2013,
title = {Characterization of Platelet Concentrates Using Dynamic Light Scattering},
author = {Labrie A, Marshall A, Bedi H, Maurer-Spurej E,},
url = {https://www.karger.com/Article/FullText/350362},
doi = {10.1159/000350362},
year = {2013},
date = {2013-04-01},
journal = {Transfusion Medicine and Hemotherapy},
volume = {40},
number = {2},
pages = {93-100},
abstract = {Background: Each year, millions of platelet transfusions save the lives of cancer patients and patients with bleeding complications. However, between 10 and 30% of all platelet transfusions are clinically ineffective as measured by corrected count increments, but no test is currently used to identify and avoid these transfusions. ThromboLUX® is the first platelet test intended to routinely characterize platelet concentrates prior to transfusion.

Methods: ThromboLUX is a non-invasive, optical test utilizing dynamic light scattering to characterize a platelet sample by the relative quantity of platelets, microparticles, and other particles present in the sample. ThromboLUX also determines the response of platelets to temperature changes. From this information the ThromboLUX score is calculated. Increasing scores indicate increasing numbers of discoid platelets and fewer microparticles. ThromboLUX uses calibrated polystyrene beads as a quality control standard, and accurately measures the size of the beads at multiple temperatures.

Results: Results from apheresis concentrates showed that ThromboLUX can determine the microparticle content in unmodified samples of platelet concentrates which correlates well with the enumeration by flow cytometry. ThromboLUX detection of microparticles and microaggregates was confirmed by microscopy.

Conclusion: ThromboLUX provides a comprehensive and novel analysis of platelet samples and has potential as a non-invasive routine test to characterize platelet products to identify and prevent ineffective transfusions.},
keywords = {Platelet Activation Status},
pubstate = {published},
tppubtype = {article}
}

@article{Xu2010,
title = {Novel test for microparticles in platelet-rich plasma and platelet concentrates using dynamic light scattering},
author = {Xu, Y., Nakane, N. and Maurer-Spurej, E.},
url = {http://onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2010.02819.x/full},
doi = {10.1111/j.1537-2995.2010.02819.x},
year = {2010},
date = {2010-08-16},
journal = {Transfusion},
volume = {51},
number = {2},
pages = {363-370},
abstract = {BACKGROUND: The level and clinical importance of platelet (PLT)-derived microparticles (PMPs) in PLT-rich plasma (PRP) and PLT transfusions is largely unknown due to the lack of technology to routinely determine the number and size of PMP in PLT samples. Dynamic light scattering (DLS) is ideally suited to measure particles of submicron size but has previously been limited to the analysis of PLT-free samples.

STUDY DESIGN AND METHODS: PMPs were enumerated in 81 PRP and 79 apheresis PLT concentrate (APC) samples from the same donors using ThromboLUX (LightIntegra Technology, Inc.), a new DLS PLT quality test. The ThromboLUX results were compared with flow cytometry. Phase contrast and differential interference contrast (DIC) microscopy were used to qualitatively determine PMP levels.

RESULTS: The relative counts of PMPs measured by flow cytometry strongly correlated with the relative light scattering intensities of the PMP determined by ThromboLUX in both PRP (R = 0.7596, p < 0.0001) and APC (R = 0.6572, p < 0.0001) samples. High or low PMP levels in PLT samples were confirmed by phase contrast and DIC microscopy. The mean PMP radius measured with ThromboLUX, an absolute sizing technology, was 117.1 ± 77.6 nm as determined from the distribution of PMP content in all PLT samples investigated in this study.

CONCLUSIONS: Correlation with flow cytometry and microscopy showed that ThromboLUX is well suited to measure PMP concentration and size distribution in PLT concentrate samples. In combination with noninvasive sampling, ThromboLUX could provide routine microparticle enumeration of PLT-containing samples.},
keywords = {dynamic light scattering, Microparticle},
pubstate = {published},
tppubtype = {article}
}

@article{Maurer-Spurej2009,
title = {Platelet quality measured with dynamic light scattering correlates with transfusion outcome in hematologic malignancies.},
author = {Maurer-Spurej, E., Labrie, A., Pittendreigh, C., Chipperfield, K., Smith, C., Heddle, N., Liu, Y., Yi, Q.-L. and Barnett, M.},
url = {http://onlinelibrary.wiley.com/wol1/doi/10.1111/j.1537-2995.2009.02302.x/full},
doi = {10.1111/j.1537-2995.2009.02302.x},
year = {2009},
date = {2009-10-22},
journal = {Transfusion},
volume = {49},
number = {11},
pages = {2276-2284},
abstract = {BACKGROUND: A clinically meaningful test for platelet (PLT) quality could improve the transfusion management of patients. The aim of this pilot study was to determine whether a new measure of PLT quality and function based on dynamic light scattering (DLS) correlates with transfusion outcome.

STUDY DESIGN AND METHODS: For a total of 160 transfusions, the pretransfusion, 1 hour posttransfusion, and 24-hour posttransfusion PLT counts were routinely measured in 49 patients (31 male, 18 female; age 46 ± 15 years) with hematologic malignancies. The corrected count increments (CCIs) at 1 hour (PLT recovery) and 24 hours (PLT survival) were calculated and used as the transfusion outcome measures. The ThromboLUX score (LightIntegra Technology, Inc., Vancouver, BC, Canada; range, 0-40; cutoff, 12) and the PLT morphology score of the PLT concentrates were determined and compared to transfusion outcome.

RESULTS: The CCIs and ThromboLUX scores were normally distributed and showed a strong correlation (n = 96, in the mixed regression model the adjusted coefficient is R = 0.6292, p < 0.0001), while other variables such as product type, age, and microscopic PLT morphology score were not correlated with transfusion outcome (p > 0.05). Importantly, 12 of 96 transfusions with poor PLT quality were clinically ineffective, that is, did not adequately increase the PLT counts in the recipients. One patient died after receiving three consecutive ineffective PLT transfusions with a low ThromboLUX score.

CONCLUSION: In this pilot study, the ThromboLUX score strongly correlated with transfusion outcome (PLT recovery and survival) independent of clinical and product issues.},
keywords = {dynamic light scattering, Platelet Activation Status, Platelet Refractoriness},
pubstate = {published},
tppubtype = {article}
}

@article{Maurer-Spurej2008,
title = {Erroneous automated optical platelet counts in 1-hour post-transfusion blood samples},
author = {Maurer-Spurej, E., Pittendreigh, C., Yakimec, J., De Badyn, M. H. and Chipperfield, K.},
url = {http://onlinelibrary.wiley.com/doi/10.1111/j.1751-553X.2008.01097.x/full},
doi = {10.1111/j.1751-553X.2008.01097.x},
year = {2008},
date = {2008-08-25},
journal = {International Journal of Laboratory Hematology},
volume = {32},
number = {1},
pages = {e1-e8},
keywords = {Analyzers},
pubstate = {published},
tppubtype = {article}
}

@article{Maurer-Spurej2008b,
title = {Routine Quality Testing of Blood Platelet Transfusions with Dynamic Light Scattering},
author = {Maurer-Spurej, E., Labrie, A. and Brown, K.},
url = {http://onlinelibrary.wiley.com/doi/10.1002/ppsc.200700017/pdf},
doi = {10.1002/ppsc.200700017},
year = {2008},
date = {2008-02-12},
journal = {Particle & Particle Systems Characterization},
volume = {25},
number = {1},
pages = {99-104},
abstract = {Extension of the current 5-day shelf life of platelet concentrates to increase the supply of this life saving blood product will require quality testing. However, no automated test exists to routinely measure the quality of platelet concentrates for transfusion. Platelet concentrates cannot be sampled and diluted. These practical limitations have prevented the routine use of optical methods for platelet quality testing. The Dynamic Light Scattering Platelet Monitor (DLS-PM) addresses these limitations. The DLS-PM is a portable instrument with a temperature-controlled sample holder to accommodate a wide range of sample containers. The challenges of small sample size, short light path through the sample, and accurate temperature control have been solved. The DLS-PM measures platelet size, number of platelet-derived microparticles, and the response of platelets to temperature changes, which are combined to calculate a platelet quality score. In this paper we introduce the DLS-PM and discuss the advantages and challenges for dynamic light scattering to become a clinically relevant, routinely used platelet test.},
keywords = {Analyzers, dynamic light scattering},
pubstate = {published},
tppubtype = {article}
}

@article{Maurer-Spurej2007,
title = {Past and Future Approaches to Assess the Quality of Platelets for Transfusion},
author = {Elisabeth Maurer-Spurej and Kate Chipperfield},
url = {http://www.tmreviews.com/article/S0887-7963(07)00044-2/fulltext},
doi = {10.1016/j.tmrv.2007.05.005},
year = {2007},
date = {2007-10-01},
journal = {Transfusion Medicine Review},
volume = {21},
number = {4},
pages = {295-306},
abstract = {Abstract
Full Text
Images
References
No automated test exists to routinely measure platelet quality. Currently, the short, 5-day shelf life of platelet concentrates is largely dictated by the risk associated with bacterial contamination and not by platelet quality. With the implementation of bacterial testing and pathogen inactivation, platelet quality will become the major determinant for the shelf life of platelet concentrates. However, extended use of platelet concentrates stored beyond 5 days will require quality testing. In addition, high platelet quality would be expected to result in improved clinical efficacy, determined by count increment, improved hemostasis, and lower risk for adverse reactions in recipients. No in vitro quality test has yet demonstrated a good correlation with clinical efficacy or improved hemostasis. This review focuses on those tests of platelet quality that are based on platelet morphology. These include visual inspection of swirling, microscopic morphology score, measurement of light transmission through platelet concentrates, and platelet light scattering techniques. Recently, a new test for platelet quality has been introduced that uses dynamic light scattering. The advantages and remaining challenges for dynamic light scattering before it can become a routine platelet quality test are discussed.},
keywords = {Platelet Activation Status},
pubstate = {published},
tppubtype = {article}
}

@article{Maurer-Spurej2006,
title = {Portable dynamic light scattering instrument and method for the measurement of blood platelet suspensions},
author = {Elisabeth Maurer-Spurej et al },
url = {http://iopscience.iop.org/article/10.1088/0031-9155/51/15/010/meta},
doi = {10.1088/0031-9155/51/15/010},
year = {2006},
date = {2006-07-20},
journal = {Physics in Medicine & Biology},
volume = {51},
number = {15},
pages = {3747},
abstract = {No routine test exists to determine the quality of blood platelet transfusions although every year millions of patients require platelet transfusions to survive cancer chemotherapy, surgery or trauma. A new, portable dynamic light scattering instrument is described that is suitable for the measurement of turbid solutions of large particles under temperature-controlled conditions. The challenges of small sample size, short light path through the sample and accurate temperature control have been solved with a specially designed temperature-controlled sample holder for small diameter, disposable capillaries. Efficient heating and cooling is achieved with Peltier elements in direct contact with the sample capillary. Focusing optical fibres are used for light delivery and collection of scattered light. The practical use of this new technique was shown by the reproducible measurement of latex microspheres and the temperature-induced morphological changes of human blood platelets. The measured parameters for platelet transfusions are platelet size, number of platelet-derived microparticles and the response of platelets to temperature changes. This three-dimensional analysis provides a high degree of confidence for the determination of platelet quality. The experimental data are compared to a matrix and facilitate automated, unbiased quality testing.},
keywords = {Analyzers, dynamic light scattering},
pubstate = {published},
tppubtype = {article}
}

@article{Maurer-Spurej2001,
title = {Platelet Aggregation Is Not Initiated by Platelet Shape Change},
author = {Elisabeth Maurer-Spurej and Dana V Devine},
url = {https://www.nature.com/articles/3780365},
doi = {10.1038/labinvest.3780365},
year = {2001},
date = {2001-11-01},
journal = {Laboratory Investigation},
volume = {81},
number = {11},
pages = {1517-1525},
abstract = {Because the initial decrease in light transmission in platelet aggregometry is attributed to platelet shape change, it is widely held that platelet shape change is a prerequisite for platelet aggregation. We conducted this study to determine the basis of this initial optical effect in aggregometry. Platelets were activated with ADP, thrombin, or the thrombin receptor agonist peptide SFLLRN (TRAP1–6). In every case the initial decrease in light transmission occurred with the concomitant formation of microaggregates. This was also seen when preactivated platelets, which cannot undergo further morphological changes, were used, and when platelets were activated in the presence of shape-change inhibitors such as cytochalasin D and vincristine. Microscopy analysis of samples fixed at minimum light transmission in the aggregometer, which is generally assumed to signal shape change, always showed the presence of microaggregates. Microaggregation appeared to be distinct from full aggregation, as it was not inhibited by the addition of CD61, an antibody to the β3 integrin. To model these findings, fibrinogen-coated latex spheres, which cannot change shape, were aggregated with thrombin; the initial decrease in light transmission was still seen, and microaggregates formed at this time. These results indicate that platelet shape change is not a prerequisite for aggregation and that the signal widely believed to represent shape change reflects platelet microaggregation instead. We conclude that platelet aggregation occurs independently of shape change and that shape change is not necessarily followed by aggregation. These observations suggest an alternative role for platelet shape change of single platelets.},
keywords = {Analyzers},
pubstate = {published},
tppubtype = {article}
}

@article{Maurer-Spurej2001b,
title = {Room Temperature Activates Human Blood Platelets},
author = {Maurer-Spurej, E., Pfeiler, G., Maurer, N., Linder, H., Glatter, O., Devine, D.},
url = {https://www.nature.com/articles/3780267},
doi = {10.1038/labinvest.3780267},
year = {2001},
date = {2001-04-01},
journal = {Laboratory Investigation},
volume = {81},
number = {4},
pages = {581-592},
abstract = {Temperatures ranging from room temperature (20° C) to 42° C are generally not considered to have an activating effect on platelets. However, this assumption is not supported by clinical phenomena that result in hemostatic failure related to hypothermia. In this study, we investigated the effect of temperatures between room temperature (20° C) and 42° C on human blood platelets and found that room temperature causes marked activation of platelets. Major changes in platelet morphology were seen at 20° C compared to resting platelets at 37° C. Platelet morphology was investigated with noninvasive live cell techniques (light microscopy and dynamic and static light scattering), as well as with transmission and scanning electron microscopy. The changes in platelet morphology correlated with the expression of the activation marker, activated glycoprotein (GP) IIb-IIIa, measured by flow cytometry. Twenty-five percent to 30% of platelets expressed activated GPIIb-IIIa after exposure to 20° C for 10 minutes. In the presence of serotonin re-uptake inhibitors, the serotonin content of platelets at 20° C was twice that of resting platelets. In comparison, moderate heat shock conditions (42° C for 10 minutes) caused no signs of platelet activation as indicated by the absence of morphological alterations, no expression of activated GPIIb-IIIa, and no changes in serotonin content. These results show that room temperature by itself significantly activates platelets and has an effect on the platelet serotonin content. This may contribute to both the functional lesion associated with 22° C storage of platelets for transfusion and the in vivo hemostatic failure after hypothermia.},
keywords = {Analyzers},
pubstate = {published},
tppubtype = {article}
}