Publications on platelet quality, function and measurement
Publications
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- Platelet quality measured with dynamic light scattering correlates with transfusion outcome in hematologic malignancies. Transfusion 2009; 49: in print.
- Erroneous automated optical platelet counts in 1-hour post-transfusion blood samples. Int J Lab Hematol 2008; DOI: 10.1111/j.1751-553X.2008.01097.x.
- Routine Quality Testing of Blood Platelet Transfusions with Dynamic Light Scattering. Particles & Particle Systems Characterization, 2008; 25:99-104.
- Past and future approaches to assess the quality of platelet concentrates for transfusion. Transfusion Med Rev. 2007; 21(4): 295-305.
- Portable dynamic light scattering instrument and method for the measurement of blood platelet suspensions. Phys Med Biol 2006; 51: 3747-3758.
- Platelet aggregation is not initiated by platelet shape change. Lab Invest 2001; 81(11):1517-1526.
- Room temperature activates human blood platelets. Lab Invest 2001; 81(4):581-592.
Maurer-Spurej E, Labrie A, Pittendreigh C, Chipperfield K, Smith C, Heddle N, Liu Y, Yi Q-L, Barnett M. Platelet quality measured with dynamic light scattering correlates with transfusion outcome in hematologic malignancies. Transfusion 2009; 49: in print.
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.
Maurer-Spurej E, Pittendreigh C, Yakimec J, Hudoba De Badyn M, Chipperfield K. Erroneous automated optical platelet counts in 1-hour post-transfusion blood samples. Int J Lab Hematol 2008; DOI: 10.1111/j.1751-553X.2008.01097.x.
Thrombocytopenic patients with acute leukemia may show high post-transfusion count increments that significantly exceed the number of transfused platelets. This study demonstrates that the automated hematology analyzer Sysmex XE-2100 reports erroneously high optical platelet counts when the blood sample contains particles in the size range of platelets or smaller. Thrombocytopenic or low-normal whole blood samples were spiked with 1 mum latex beads (n = 14) to mimic contaminants under controlled conditions. Optical and impedance measurements of spiked and control samples with the Sysmex XE-2100 were compared with the Advia 120 and the manual counts. The added beads unexpectedly increased the automated optical platelet counts in the Sysmex XE-2100 and, to a lesser extent, the Advia 120 (Wilcoxon signed ranks test, P < 0.05), while the beads were not included in the impedance or the manual microscopic platelet counts. Differential interference contrast microscopy was used to investigate samples from platelet concentrates for transfusion. Platelet concentrates (32/128) were identified as possible sources for particles that were microscopically distinct from platelets but would be included in the automated optical count. Transfusion of platelet concentrates containing contaminating particles can lead to unexpectedly high post-transfusion platelet counts and misdiagnosis of thrombocytopenic patients.
Maurer-Spurej E, Labrie A, Brown K. Routine Quality Testing of Blood Platelet Transfusions with Dynamic Light Scattering. Particles & Particle Systems Characterization, 2008; 25:99-104.
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.
Maurer-Spurej E, Chipperfield K. Past and future approaches to assess the quality of platelet concentrates for transfusion. Transfusion Med Rev. 2007; 21(4): 295-305.
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.
Maurer-Spurej E, Brown K, Labrie A, Marziali A, Glatter O. Portable dynamic light scattering instrument and method for the measurement of blood platelet suspensions. Phys Med Biol 2006; 51: 3747-3758.
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.
Maurer-Spurej E, Devine DV. Platelet aggregation is not initiated by platelet shape change. Lab Invest 2001; 81(11):1517-1526.
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 (TRAP(1-6)). 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 beta(3) 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.
Maurer-Spurej E, Pfeiler G, Maurer N, Lindner H, Glatter O, Devine DV. Room temperature activates human blood platelets. Lab Invest 2001; 81(4):581-592.
Temperatures ranging from room temperature (20 degrees C) to 42 degrees 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 degrees C) and 42 degrees C on human blood platelets and found that room temperature causes marked activation of platelets. Major changes in platelet morphology were seen at 20 degrees C compared to resting platelets at 37 degrees 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 degrees C for 10 minutes. In the presence of serotonin re-uptake inhibitors, the serotonin content of platelets at 20 degrees C was twice that of resting platelets. In comparison, moderate heat shock conditions (42 degrees 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 degrees C storage of platelets for transfusion and the in vivo hemostatic failure after hypothermia.