Download PDF
Hamostaseologie 2020; 40(04): 500-508
DOI: 10.1055/a-1210-3229
Review Article

What about Platelet Function in Platelet Concentrates?

Michel Prudent
1   Laboratoire de Recherche sur les Produits Sanguins, Recherche et Développement Produits, Transfusion Interrégionale CRS, Epalinges, Switzerland
2   Centre de transfusion Sanguine, Faculté de Biologie et de Médecine, University of Lausanne, Lausanne, Switzerland
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

The characterization of platelet concentrates (PCs) in transfusion medicine has been performed with different analytical methods and platelet lesions (from biochemistry to cell biology) have been documented. In routine quality assessment and validation of manufacturing processes of PCs for transfusion purposes, only basic parameters are monitored and the platelet functions are not included. However, PCs undergo several manipulations during the processing and the basic parameters do not provide sensitive analyses to properly picture out the impact of the blood component preparation and storage on platelets. To improve the transfusion supply chain and the platelet functionalities, additional parameters should be used. The present short review will focus on the different techniques to monitor ex vivo platelet lesions from phenotype characterization to advanced omic analyses. Then, the opportunities to use these methods in quality control, process validation, development, and research will be discussed. Functional markers should be considered because they would be an advantage for the future developments in transfusion medicine.

Zusammenfassung

Die Charakterisierung von Thrombozytenkonzentraten (TK) wird in der Transfusionsmedizin mithilfe von verschiedenen analytischen Methoden durchgeführt und dabei können Thrombozytenläsionen (von der biochemischen bis zur zellulären Ebene) festgestellt werden. In der routinemässigen Qualitätsprüfung und bei der Validierung von Herstellungsverfahren von TK für Transfusionszwecke werden nur grundlegende Parameter überprüft, allerdings nicht die Thrombozytenfunktion. TK erfahren jedoch mehrere Bearbeitungsschritte während der Herstellung und die Analyze der Standardparameter ist nicht ausreichend um den Einfluss der Blutkomponentenherstellung und der Lagerung auf Thrombozyten zu erfassen. Um die Transfusionsversorgungskette und die Funktionalität der Thrombozyten zu verbessern, sollten zusätzliche Parameter berücksichtigt werden. In diesem kurzen Review liegt der Fokus auf verschiedene Techniken um ex vivo Thrombozytenläsionen, durch Phänotypcharakterisierung bis hin zu modernsten Omik-Analysen, aufzuzeigen. Anschliessend wird der Nutzen dieser Methoden für Qualitätskontrolle, Prozessvalidierung, Entwicklung und Forschung diskutiert. Funktionsmarker sollten berücksichtigt werden, da sie einen Vorteil für zukünftige Entwicklungen in der Transfusionsmedizin darstellen würden.

Keywords

monitoring - platelet - quality control - transfusion medicine

Schlüsselwörter

Monitoring - Thrombozyt - Qualitätskontrolle - Transfusionsmedizin


Publication History

Received: 15 May 2020

Accepted: 29 June 2020

Article published online:
15 September 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Shrivastava M. The platelet storage lesion. Transfus Apheresis Sci 2009; 41 (02) 105-113
    CrossrefPubMedGoogle Scholar
  • 2 Tissot JD, Bardyn M, Sonego G, Abonnenc M, Prudent M. The storage lesions: from past to future. Transfus Clin Biol 2017; 24 (03) 277-284
    CrossrefPubMedGoogle Scholar
  • 3 EDQM. Guide to the Preparation, Use and Quality Assurance of Blood Components. 19th ed.. Strasbourg: European Directorate for the Quality of Medicines & HealthCare, Council of Europe; 2017
    Google Scholar
  • 4 van der Meer PF, de Korte D. Platelet additive solutions: a review of the latest developments and their clinical implications. Transfus Med Hemother 2018; 45 (02) 98-102
    CrossrefPubMedGoogle Scholar
  • 5 Seltsam A. Pathogen inactivation of cellular blood products-an additional safety layer in transfusion medicine. Front Med (Lausanne) 2017; 4: 219
    CrossrefPubMedGoogle Scholar
  • 6 Schubert P, Johnson L, Marks DC, Devine DV. Ultraviolet-based pathogen inactivation systems: untangling the molecular targets activated in platelets. Front Med (Lausanne) 2018; 5: 129
    CrossrefPubMedGoogle Scholar
  • 7 Johnson L, Tan S, Wood B, Davis A, Marks DC. Refrigeration and cryopreservation of platelets differentially affect platelet metabolism and function: a comparison with conventional platelet storage conditions. Transfusion 2016; 56 (07) 1807-1818
    CrossrefPubMedGoogle Scholar
  • 8 Braathen H, Sivertsen J, Lunde THF. et al. In vitro quality and platelet function of cold and delayed cold storage of apheresis platelet concentrates in platelet additive solution for 21 days. Transfusion 2019; 59 (08) 2652-2661
    CrossrefPubMedGoogle Scholar
  • 9 Strandenes G, Kristoffersen EK, Bjerkvig CK. et al. Cold-stored apheresis platelets in treatment of postoperative bleeding in cardiothoracic surgery. Transfusion 2016; 56: 16A-16A
    CrossrefPubMedGoogle Scholar
  • 10 Corley JB, Messenger JM, Cheser JL. et al. Implementation of cold stored platelets for combat trauma resuscitation. Transfusion 2016; 56: 16A-17A
    CrossrefPubMedGoogle Scholar
  • 11 Cap AP. Platelet storage: a license to chill!. Transfusion 2016; 56 (01) 13-16
    CrossrefPubMedGoogle Scholar
  • 12 Feys HB, Van Aelst B, Compernolle V. Biomolecular consequences of platelet pathogen inactivation methods. Transfus Med Rev 2019; 33 (01) 29-34
    CrossrefPubMedGoogle Scholar
  • 13 Garraud O, Tissot J-D. Blood and blood components: from similarities to differences. Front Med (Lausanne) 2018; 5 (84) 84
    CrossrefPubMedGoogle Scholar
  • 14 Lion N, Tissot JD, Prudent M. What can omics bring to transfusion?. Blood Transfus 2016; 14 (Suppl. 01) INV-07
    PubMedGoogle Scholar
  • 15 Prudent M, Tissot JD, Lion N. Proteomics of blood and derived products: what's next?. Expert Rev Proteomics 2011; 8 (06) 717-737
    CrossrefPubMedGoogle Scholar
  • 16 Nemkov T, Hansen KC, Dumont LJ, D'Alessandro A. Metabolomics in transfusion medicine. Transfusion 2016; 56 (04) 980-993
    CrossrefPubMedGoogle Scholar
  • 17 Abonnenc M, Crettaz D, Marvin L. et al. Metabolomic profiling highlights oxidative damages in platelet concentrates treated for pathogen inactivation and shows protective role of urate. Metabolomics 2016; 12 (12) 188
    CrossrefPubMedGoogle Scholar
  • 18 Paglia G, Sigurjónsson OE, Rolfsson Ó. et al. Comprehensive metabolomic study of platelets reveals the expression of discrete metabolic phenotypes during storage. Transfusion 2014; 54 (11) 2911-2923
    CrossrefPubMedGoogle Scholar
  • 19 Osman A, Hitzler WE, Ameur A, Provost P. Differential expression analysis by RNA-Seq reveals perturbations in the platelet mRNA transcriptome triggered by pathogen reduction systems. PLoS One 2015; 10 (07) e0133070
    CrossrefPubMedGoogle Scholar
  • 20 Prudent M, D'Alessandro A, Cazenave J-P. et al. Proteome changes in platelets after pathogen inactivation--an interlaboratory consensus. Transfus Med Rev 2014; 28 (02) 72-83
    CrossrefPubMedGoogle Scholar
  • 21 Abonnenc M, Sonego G, Crettaz D. et al. In vitro study of platelet function confirms the contribution of the ultraviolet B (UVB) radiation in the lesions observed in riboflavin/UVB-treated platelet concentrates. Transfusion 2015; 55 (09) 2219-2230
    CrossrefPubMedGoogle Scholar
  • 22 Abonnenc M, Crettaz D, Sonego G, Escolar G, Tissot JD, Prudent M. Towards the understanding of the UV light, riboflavin and additive solution contributions to the in vitro lesions observed in Mirasol®-treated platelets. Transfus Clin Biol 2019; 26 (04) 209-216
    CrossrefPubMedGoogle Scholar
  • 23 Hechler B, Ohlmann P, Chafey P. et al. Preserved functional and biochemical characteristics of platelet components prepared with amotosalen and ultraviolet A for pathogen inactivation. Transfusion 2013; 53 (06) 1187-1200
    CrossrefPubMedGoogle Scholar
  • 24 Stivala S, Gobbato S, Infanti L. et al. Amotosalen/ultraviolet A pathogen inactivation technology reduces platelet activatability, induces apoptosis and accelerates clearance. Haematologica 2017; 102 (10) 1650-1660
    CrossrefPubMedGoogle Scholar
  • 25 Van Aelst B, Devloo R, Vandekerckhove P, Compernolle V, Feys HB. Ultraviolet C light pathogen inactivation treatment of platelet concentrates preserves integrin activation but affects thrombus formation kinetics on collagen in vitro. Transfusion 2015; 55 (10) 2404-2414
    CrossrefPubMedGoogle Scholar
  • 26 Picker SM, Tauszig ME, Gathof BS. Cell quality of apheresis-derived platelets treated with riboflavin-ultraviolet light after resuspension in platelet additive solution. Transfusion 2012; 52 (03) 510-516
    CrossrefPubMedGoogle Scholar
  • 27 Bertaggia Calderara D, Crettaz D, Aliotta A. et al. Generation of procoagulant collagen- and thrombin-activated platelets in platelet concentrates derived from buffy coat: the role of processing, pathogen inactivation, and storage. Transfusion 2018; 58 (10) 2395-2406
    CrossrefPubMedGoogle Scholar
  • 28 Kiminkinen LK, Krusius T, Javela KM. Evaluation of soluble glycoprotein V as an in vitro quality marker for platelet concentrates: a correlation study between in vitro platelet quality markers and the effect of storage medium. Vox Sang 2016; 111 (02) 120-126
    CrossrefPubMedGoogle Scholar
  • 29 Chen Z, Schubert P, Culibrk B, Devine DV. p38MAPK is involved in apoptosis development in apheresis platelet concentrates after riboflavin and ultraviolet light treatment. Transfusion 2015; 55 (04) 848-857
    CrossrefPubMedGoogle Scholar
  • 30 Reid S, Johnson L, Woodland N, Marks DC. Pathogen reduction treatment of buffy coat platelet concentrates in additive solution induces proapoptotic signaling. Transfusion 2012; 52 (10) 2094-2103
    CrossrefPubMedGoogle Scholar
  • 31 Keuren JF, Cauwenberghs S, Heeremans J, de Kort W, Heemskerk JW, Curvers J. Platelet ADP response deteriorates in synthetic storage media. Transfusion 2006; 46 (02) 204-212
    CrossrefPubMedGoogle Scholar
  • 32 Hardy AR, Conley PB, Luo J, Benovic JL, Poole AW, Mundell SJ. P2Y1 and P2Y12 receptors for ADP desensitize by distinct kinase-dependent mechanisms. Blood 2005; 105 (09) 3552-3560
    CrossrefPubMedGoogle Scholar
  • 33 Mazepa M, Hoffman M, Monroe D. Superactivated platelets: thrombus regulators, thrombin generators, and potential clinical targets. Arterioscler Thromb Vasc Biol 2013; 33 (08) 1747-1752
    CrossrefPubMedGoogle Scholar
  • 34 Heemskerk JW, Mattheij NJ, Cosemans JM. Platelet-based coagulation: different populations, different functions. J Thromb Haemost 2013; 11 (01) 2-16
    CrossrefPubMedGoogle Scholar
  • 35 Daskalakis M, Colucci G, Keller P. et al. Decreased generation of procoagulant platelets detected by flow cytometric analysis in patients with bleeding diathesis. Cytometry B Clin Cytom 2014; 86 (06) 397-409
    CrossrefPubMedGoogle Scholar
  • 36 Alberio L, Safa O, Clemetson KJ, Esmon CT, Dale GL. Surface expression and functional characterization of alpha-granule factor V in human platelets: effects of ionophore A23187, thrombin, collagen, and convulxin. Blood 2000; 95 (05) 1694-1702
    CrossrefPubMedGoogle Scholar
  • 37 Dale GL, Friese P, Batar P. et al. Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface. Nature 2002; 415 (6868): 175-179
    CrossrefPubMedGoogle Scholar
  • 38 Svendsen MS, Rojkjaer R, Kristensen AT, Salado-Jimena JA, Kjalke M, Johansson PI. Impairment of the hemostatic potential of platelets during storage as evaluated by flow cytometry, thrombin generation, and thrombelastography under conditions promoting formation of coated platelets. Transfusion 2007; 47 (11) 2057-2065
    CrossrefPubMedGoogle Scholar
  • 39 Charania R, Smith J, Vesely SK, Dale GL, Holter J. Quantitation of coated platelet potential during collection, storage, and transfusion of apheresis platelets. Transfusion 2011; 51 (12) 2690-2694
    CrossrefPubMedGoogle Scholar
  • 40 Gerber B, Alberio L, Rochat S. et al. Safety and efficacy of cryopreserved autologous platelet concentrates in HLA-alloimmunized patients with hematologic malignancies. Transfusion 2016; 56 (10) 2426-2437
    CrossrefPubMedGoogle Scholar
  • 41 Ponschab M, Schöchl H, Gabriel C. et al. Haemostatic profile of reconstituted blood in a proposed 1:1:1 ratio of packed red blood cells, platelet concentrate and four different plasma preparations. Anaesthesia 2015; 70 (05) 528-536
    CrossrefPubMedGoogle Scholar
  • 42 Ågren A, Edgren G, Ambrosio D, Gryfelt G, Östlund A, Wikman A. Haemostasis monitored in stored red blood cells, plasma and platelet concentrates in the proportion of 4: 4: 1 diluted with crystalloids and colloids. Blood Coagul Fibrinolysis 2016; 27 (03) 334-339
    CrossrefPubMedGoogle Scholar
  • 43 Labrie A, Marshall A, Bedi H, Maurer-Spurej E. Characterization of platelet concentrates using dynamic light scattering. Transfus Med Hemother 2013; 40 (02) 93-100
    CrossrefPubMedGoogle Scholar
  • 44 Maurer-Spurej E, Labrie A, Pittendreigh C. et al. Platelet quality measured with dynamic light scattering correlates with transfusion outcome in hematologic malignancies. Transfusion 2009; 49 (11) 2276-2284
    CrossrefPubMedGoogle Scholar
  • 45 Leitner GC, List J, Horvath M, Eichelberger B, Panzer S, Jilma-Stohlawetz P. Additive solutions differentially affect metabolic and functional parameters of platelet concentrates. Vox Sang 2016; 110 (01) 20-26
    CrossrefPubMedGoogle Scholar
  • 46 Prudent M, Sonego G, Abonnenc M, Tissot J-D, Lion N. LC-MS/MS analysis and comparison of oxidative damages on peptides induced by pathogen reduction technologies for platelets. J Am Soc Mass Spectrom 2014; 25 (04) 651-661
    CrossrefPubMedGoogle Scholar
  • 47 Johnson L, Marks D. Treatment of platelet concentrates with the mirasol pathogen inactivation system modulates platelet oxidative stress and NF-κB activation. Transfus Med Hemother 2015; 42 (03) 167-173
    CrossrefPubMedGoogle Scholar
  • 48 Green SM, Padula MP, Marks DC, Johnson L. The lipid composition of platelets and the impact of storage: an overview. Transfus Med Rev 2020; 34 (02) 108-116
    CrossrefPubMedGoogle Scholar
  • 49 Lion N, Tissot JD, Prudent M. Is proteomics still knockin' on the hematological door?. Proteomics Clin Appl 2016; 10 (08) 765-766
    CrossrefPubMedGoogle Scholar
  • 50 García A, Prabhakar S, Brock CJ. et al. Extensive analysis of the human platelet proteome by two-dimensional gel electrophoresis and mass spectrometry. Proteomics 2004; 4 (03) 656-668
    CrossrefPubMedGoogle Scholar
  • 51 Qureshi AH, Chaoji V, Maiguel D. et al. Proteomic and phospho-proteomic profile of human platelets in basal, resting state: insights into integrin signaling. PLoS One 2009; 4 (10) e7627
    CrossrefPubMedGoogle Scholar
  • 52 Burkhart JM, Vaudel M, Gambaryan S. et al. The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional pathways. Blood 2012; 120 (15) e73-e82
    CrossrefPubMedGoogle Scholar
  • 53 Salunkhe V, De Cuyper IM, Papadopoulos P. et al. A comprehensive proteomics study on platelet concentrates: platelet proteome, storage time and Mirasol pathogen reduction technology. Platelets 2019; 30 (03) 368-379
    CrossrefPubMedGoogle Scholar
  • 54 Sonego G, Abonnenc M, Crettaz D, Lion N, Tissot JD, Prudent M. Irreversible oxidations of platelet proteins after riboflavin-UVB pathogen inactivation. Transfus Clin Biol 2020; 27 (01) 36-42
    CrossrefPubMedGoogle Scholar
  • 55 Aloui C, Barlier C, Claverol S. et al. Differential protein expression of blood platelet components associated with adverse transfusion reactions. J Proteomics 2019; 194: 25-36
    CrossrefPubMedGoogle Scholar
  • 56 Prudent M, Crettaz D, Delobel J, Tissot J-D, Lion N. Proteomic analysis of Intercept-treated platelets. J Proteomics 2012; 76 (Spec No): 316-328
    CrossrefPubMedGoogle Scholar
  • 57 García A, Prabhakar S, Hughan S. et al. Differential proteome analysis of TRAP-activated platelets: involvement of DOK-2 and phosphorylation of RGS proteins. Blood 2004; 103 (06) 2088-2095
    CrossrefPubMedGoogle Scholar
  • 58 Beck F, Geiger J, Gambaryan S. et al. Temporal quantitative phosphoproteomics of ADP stimulation reveals novel central nodes in platelet activation and inhibition. Blood 2017; 129 (02) e1-e12
    CrossrefPubMedGoogle Scholar
  • 59 Schubert P, Coupland D, Culibrk B, Goodrich RP, Devine DV. Riboflavin and ultraviolet light treatment of platelets triggers p38MAPK signaling: inhibition significantly improves in vitro platelet quality after pathogen reduction treatment. Transfusion 2013; 53 (12) 3164-3173
    CrossrefPubMedGoogle Scholar
  • 60 Sonego G, Abonnenc M, Tissot J-D, Prudent M, Lion N. Redox proteomics and platelet activation: understanding the redox proteome to improve platelet quality for transfusion. Int J Mol Sci 2017; 18 (02) 1-22
    CrossrefPubMedGoogle Scholar
  • 61 Verhaar R, Dekkers DWC, De Cuyper IM, Ginsberg MH, de Korte D, Verhoeven AJ. UV-C irradiation disrupts platelet surface disulfide bonds and activates the platelet integrin alphaIIbbeta3. Blood 2008; 112 (13) 4935-4939
    CrossrefPubMedGoogle Scholar
  • 62 Sonego G, Le T-TM, Crettaz D, Abonnenc M, Tissot JD, Prudent M. Sulfenylome analysis of pathogen-inactivated platelets reveals the role of cysteine oxidation in integrin aIIbbIII-mediated platelet activation. Submitted
    Google Scholar
  • 63 Cardigan R, Turner C, Harrison P. Current methods of assessing platelet function: relevance to transfusion medicine. Vox Sang 2005; 88 (03) 153-163
    CrossrefPubMedGoogle Scholar
  • 64 Saris A, Kreuger AL, Ten Brinke A. et al. The quality of platelet concentrates related to corrected count increment: linking in vitro to in vivo. Transfusion 2019; 59 (02) 697-706
    CrossrefPubMedGoogle Scholar
  • 65 Heddle NM, Arnold DM, Webert KE. Time to rethink clinically important outcomes in platelet transfusion trials. Transfusion 2011; 51 (02) 430-434
    CrossrefPubMedGoogle Scholar
  • 66 Slichter SJ. Relationship between platelet count and bleeding risk in thrombocytopenic patients. Transfus Med Rev 2004; 18 (03) 153-167
    CrossrefPubMedGoogle Scholar
  • 67 Opheim EN, Apelseth TO, Stanworth SJ, Eide GE, Hervig T. Thromboelastography may predict risk of grade 2 bleeding in thrombocytopenic patients. Vox Sang 2017; 112 (06) 578-585
    CrossrefPubMedGoogle Scholar
  • 68 Heddle NM, Cardoso M, van der Meer PF. Revisiting study design and methodology for pathogen reduced platelet transfusions: a round table discussion. Transfusion 2020; 60 (07) 1604-1611
    CrossrefPubMedGoogle Scholar
  • 69 Kuruvilla DJ, Widness JA, Nalbant D. et al. Estimation of adult and neonatal RBC lifespans in anemic neonates using RBCs labeled at several discrete biotin densities. Pediatr Res 2017; 81 (06) 905-910
    CrossrefPubMedGoogle Scholar
  • 70 Mock DM, Lankford GL, Widness JA, Burmeister LF, Kahn D, Strauss RG. Measurement of circulating red cell volume using biotin-labeled red cells: validation against 51Cr-labeled red cells. Transfusion 1999; 39 (02) 149-155
    CrossrefPubMedGoogle Scholar
  • 71 Mock DM, Widness JA, Veng-Pedersen P. et al. Measurement of posttransfusion red cell survival with the biotin label. Transfus Med Rev 2014; 28 (03) 114-125
    CrossrefPubMedGoogle Scholar
  • 72 Alberio L, Dale GL. Platelet biotinylation for monitoring in vivo survival and cellular function. Platelets 1997; 8 (06) 373-378
    CrossrefPubMedGoogle Scholar
  • 73 Stohlawetz P, Horvath M, Pernerstorfer T. et al. Effects of nitric oxide on platelet activation during plateletpheresis and in vivo tracking of biotinylated platelets in humans. Transfusion 1999; 39 (05) 506-514
    CrossrefPubMedGoogle Scholar
  • 74 Ravanat C, Heim V, Pongerard A, Dupuis A, Gachet C. Les plaquettes humaines marquées à différentes densités de biotine: une approche prometteuse pour la mesure simultanée de la survie de plaquettes in vivo dans des études cliniques. Transfus Clin Biol 2018; 25 (04) 323-324
    CrossrefPubMedGoogle Scholar
  • 75 de Bruin S, van de Weerdt EK, Sijbrands D. et al. Biotinylation of platelets for transfusion purposes a novel method to label platelets in a closed system. Transfusion 2019; 59 (09) 2964-2973
    CrossrefPubMedGoogle Scholar
  • 76 Spitalnik SL, Triulzi D, Devine DV. et al; State of the Science in Transfusion Medicine Working Groups. 2015 proceedings of the National Heart, Lung, and Blood Institute's State of the Science in Transfusion Medicine symposium. Transfusion 2015; 55 (09) 2282-2290
    CrossrefPubMedGoogle Scholar