Prevention of Cytokine Accumulation in Platelets Obtained with the COBE Spectra Apheresis System

Abstract

Background and Objectives: Febrile nonhemolytic transfusion reactions frequently accompany platelet transfusions and may be due to accumulation of cytokines mediating inflammation during storage of platelet concentrates (PCs). We wished to determine whether PCs collected using the COBE® SpectraTM Apheresis System (Version 4) were sufficiently leukocyte reduced (LR) to limit cytokine accumulation during storage. Materials and Methods: Cytokine accumulation – interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α) – and release of platelet α-granule – P-selectin, transforming growth factor-β1 (TGF-β1), platelet-derived growth factor AB (PDGF-AB), von Willebrand factor (vWf) – or dense granule (serotonin) markers were investigated during a 7-day storage period comparing apheresis-collected, LR PCs (LR PCs) and random donor platelets prepared from whole blood (WB). Results: Leukocyte counts were reduced 99.95% comparing LR PCs (5.7 × 10⁵/l) and WB PCs (1.09 × 10⁹/l). Little or no accumulation of leukocyte-derived cytokines was observed in LR PCs during storage in contrast to WB PCs. A reduction in the release of platelet α-granule proteins, such as P-selectin, TGF-β1 and PDGF-AB, was observed on day 0 for LR PCs compared to WB PCs with little or no difference observed from day 3 to 7. Plasma vWf levels were higher in LR PCs compared to WB PCs on days 0–7. Conclusion: Leukocyte levels in PCs collected with the COBE Spectra Apheresis System are sufficiently low to limit cytokine production during 7 days of storage.

Temporal growth factor release from platelet‐rich plasma, trehalose lyophilized platelets, and bone marrow aspirate and their effect on tendon and ligament gene expression

“…52 Furthermore, IL-1b and TNF-a released from inflammatory cells stimulate MMP expression and synthesis in tenocytes without a change in tissue inhibitors of metalloproteinases resulting in a shift away from tissue homeostasis towards degeneration. 44,53 Several investigators have established that there is a positive correlation between increasing leukocyte concentration in platelet concentrates and accumulation of inflammatory cytokines including IL-1b, TNF-a, IL-6, and IL-8 from 2 to 7 days of storage at room temperature, [54][55][56][57][58][59] and in the present study, we establish that WBC concentration in treatment products is positively correlated with catabolic gene expression in tendons and ligaments.…”

“…55 Leukocyte-reduced PRP prepared by a variety of methods contains undetectable to low concentrations at the limit of detection of ILs and TNF-a, and the concentrations of these molecules does not increase over time. 54,[56][57][58][59][60] These methods of WBC reduction do not affect platelet a-granule release compared to nonleukocyte reduced PRP between 3 and 7 days, although high leukocyte concentration PRP does demonstrate greater platelet activation at the initiation of storage. 58,59 Reported maximum WBC concentrations to prevent inflammatory cytokine accumulation range from 0.1-3 Â 10 3 WBC/mL for all cytokines evaluated and 9.2 Â 10 3 WBC/mL for IL-6.…”

“…54,[56][57][58][59][60] These methods of WBC reduction do not affect platelet a-granule release compared to nonleukocyte reduced PRP between 3 and 7 days, although high leukocyte concentration PRP does demonstrate greater platelet activation at the initiation of storage. 58,59 Reported maximum WBC concentrations to prevent inflammatory cytokine accumulation range from 0.1-3 Â 10 3 WBC/mL for all cytokines evaluated and 9.2 Â 10 3 WBC/mL for IL-6. 55,57,59 The results of the present investigation are consistent with the previous reports, keeping in mind that MMP expression is stimulated by ILs and TNF-a.…”

“…58,59 Reported maximum WBC concentrations to prevent inflammatory cytokine accumulation range from 0.1-3 Â 10 3 WBC/mL for all cytokines evaluated and 9.2 Â 10 3 WBC/mL for IL-6. 55,57,59 The results of the present investigation are consistent with the previous reports, keeping in mind that MMP expression is stimulated by ILs and TNF-a. The mean concentration of WBCs in BMA was seven times the highest value reported to prevent inflammatory cytokine accumulation, and BMA-treated tendon and ligament had the greatest overall expression of MMPs.…”

Different preparation methods to obtain platelet components as a source of growth factors for local application

“…Other researchers reported an approximate accumulation of three to five times the levels of PDGF and TGF-β1 in the supernatants of platelet components during storage. [27][28][29][30][31] We found an accumulation of these growth factors in the supernatants of only about twice the baseline amount. This accumulation was much lower than the synchronous decrease in the total supernatant plus intracellular growth factor content.…”