Cytokine levels as performance indicators for white blood cell reduction of platelet concentrates

Wadhwa, Meenu; Krailadsiri, Pranee; Dilger, Paula; Das, Rose Gaines; Seghatchian, M.J.; Thorpe, Robin

doi:10.1046/j.1423-0410.2002.00203.x

Cited by 36 publications

(33 citation statements)

References 51 publications

(80 reference statements)

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“…However, technical differences cannot be entirely excluded as the source of this. The levels of PLT-derived cytokines measured in our study are comparable to previous findings reporting wide ranges, especially for CXCL4 (PLT factor 4) [3,[29][30][31][32][33][34][35]. As reported previously, neither prestorage leukoreduction nor PRT treatment or gamma irradiation could prevent the accumulation of TGF-β1, CCL5 (RANTES), and CXCL4 (PLT factor 4) [13,33].…”

Section: Discussionsupporting

confidence: 89%

Evaluation of White Blood Cell- and Platelet-Derived Cytokine Accumulation in MIRASOL-PRT-Treated Platelets

Picker

Steisel

Gathof³

2009

Transfus Med Hemother

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Background: Soluble mediators in platelet concentrates (PCs) released from contaminating white blood cells (WBCs) and platelets (PLTs) themselves are supposed to promote allergic and non-hemolytic febrile transfusion reactions in the recipient. Pathogen reduction technologies (PRTs) prevent replication and proliferation of pathogens as well as of WBCs, and may reduce cytokine accumulation in PCs during storage and prevent adverse events after PLT transfusion. On the other hand, such treatments may also lead to increased cytokine production by stimulation of WBCs or PLTs due to the photochemical or photodynamical process itself. Material and Methods: 12 triple-dose PLT apheresis collections were leukoreduced by the process-controlled leukoreduction system of the Trima Accel machine and split into 3 units undergoing Mirasol-PRT treatment (M) or gamma irradiation (X) or remaining untreated (C). During storage for up to 7 days, PLT activation, WBC-derived Th-1/2, and inflammatory as well as PLT-derived cytokines were measured by cytometric bead array and enzymelinked immunosorbent assay, respectively. Results: Independent of treatment, all PLT products exhibited low levels of WBC-associated cytokines near or below assay detection limits. WBC-associated cytokines were not elevated by Mirasol-PRT treatment. PLT-derived cytokines were detected at higher levels and increased significantly during storage in all units. Most likely due to higher PLT activation, M units showed significantly higher levels of PLT-derived cytokines compared to untreated and gamma-irradiated units on day 5 of storage. Conclusion: In all PCs, PLTs themselves were the main source of cytokine release. Mirasol-PRT treatment was associated with a significantly increased PLT activation and accumulation of PLT-derived cytokines during storage, without affecting WBC-derived cytokines relative to controls.

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Section: Discussionsupporting

confidence: 89%

Evaluation of White Blood Cell- and Platelet-Derived Cytokine Accumulation in MIRASOL-PRT-Treated Platelets

Picker

Steisel

Gathof³

2009

Transfus Med Hemother

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“…We validated our methodology in the light of these observations and conducted an extensive pre-analytical assessment on different preparations of plasma, to demonstrate that the MSD assay as we have optimized it, can detect reproducible and comparable levels of LTGF-b1 without any significant influence from sample preparation and anticoagulant agents used ( Figure 6). An additional source of pre-analytical variation for LTGF-b measurements is provided by leukocyte filtration/ leukapheresis implemented by blood banks to prevent alloimmunization and viruses transmission and to separate the platelet component (Heddle et al, 2002;Uhlmann et al, 2001;Wadhwa et al, 2002). TGF-b is increased in plasma of patients with hematologic malignancies after transfusion of platelet concentrates (Kunz et al, 1998); in fact, electrostatic forces and surface factors on leukocytes filters activate the complement cascade and the release of leukocyte lysosomal enzymes and other inflammatory mediators including TGF-b (Hyllner et al, 2004;Kristiansson et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Development of a novel multiplexed assay for quantification of transforming growth factor-β(TGF-β)

Pellicciotta¹,

Marciscano²,

Hardee³

et al. 2015

Growth Factors

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Changes in activity or levels of transforming growth factor-β (TGF-β) are associated with a variety of diseases; however, measurement of TGF-β in biological fluids is highly variable. TGF-β is biologically inert when associated with its latency-associated peptide (LAP). Most available immunoassays require exogenous activation by acid/heat to release TGF-β from the latent complex. We developed a novel electrochemiluminescence-based multiplexed assay on the MesoScale Discovery® platform that eliminates artificial activation, simultaneously measures both active TGF-β1 and LAP1 and includes an internal control for platelet-derived TGF-β contamination in blood specimens. We optimized this assay to evaluate plasma levels as a function of activation type and clinical specimen preparation. We determined that breast cancer patients' plasma have higher levels of circulating latent TGF-β (LTGF-β) as measured by LAP1 than healthy volunteers (p < 0.0001). This assay provides a robust tool for correlative studies of LTGF-β levels with disease, treatment outcomes and toxicity with a broad clinical applicability.

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“…This study focuses on WBC level and cytokine levels which proves that cytokine concentration is directly related to WBC content and storage time. As demonstrated by Wadhwa et al [18] cytokines have the potential to mediate some of the adverse effects of platelet transfusions by inducing the secretion of other cytokines from target cell types or by synergizing with other cytokines. It increases further by activated platelets which upon transfusion may induce WBC activation and/or secretion of pro inflammatory cytokines and strengthen inflammatory reactions.…”

Section: Discussionmentioning

confidence: 99%

Time Dependent Release of Interleukin-8 and Tumor Necrosis Factor-α in Platelet Concentrate

Shukla

Patel

Gupte

2014

Indian J Hematol Blood Transfus

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Contaminating white blood cells in stored platelet concentrate (PC) are the source of many pro-inflammatory cytokines. These are implicated in transfusion reactions. To study the release of interleukin (IL)-8 and tumor necrosis factor alpha (TNF-a) at different time interval in PC prepared byplatelet rich plasma (PRP) and buffy coat (BC) using different principles. Fifteen PCs were prepared by both the methods. The supernatants of PCs prepared by PRP and BC methods were collected aseptically after 1, 18, 65 and 112 h of preparation. pH, platelet and WBC counts were done. The supernatants were frozen in aliquots at -56°C for measurement of IL-8 and TNF-a concentration using ELISA. The Mean ± SD value of WBC in PRP-PC was 7.4 ± 3.75 9 10 7 and in BC-PC 3.9 ± 2.2 9 10 7

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Cytokine levels as performance indicators for white blood cell reduction of platelet concentrates

Abstract: These results show that markers of cytokine release from both WBCs and platelets are useful indicators of the performance and efficacy of the WBC-reduction process and of platelet quality.

Cited by 36 publications

References 51 publications

Evaluation of White Blood Cell- and Platelet-Derived Cytokine Accumulation in MIRASOL-PRT-Treated Platelets

Evaluation of White Blood Cell- and Platelet-Derived Cytokine Accumulation in MIRASOL-PRT-Treated Platelets

Development of a novel multiplexed assay for quantification of transforming growth factor-β(TGF-β)

Time Dependent Release of Interleukin-8 and Tumor Necrosis Factor-α in Platelet Concentrate

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