PRT-treated Platelets Research Articles

The effects of pathogen reduction technology on apheresis platelet concentrates stored in PAS.

The impact of pathogen reduction technology (PRT) such as Mirasol, and the effect of platelet additive solutions (PAS) on the activity and hemostatic profile of transfused apheresis platelets remain largely unknown. The aim of this study was to assess the in vitro hemostatic and metabolic profile of Mirasol treated platelets in PAS during a 7-day storage period. Ten split bags containing apheresis platelets stored in PAS were split into two groups; control platelets (No.=10 units) and PRT-treated platelets (No.=10 units). In vitro evaluation of the platelet components was performed on the 1st, 3rd, 5th, and 7th days of the storage period. Several metabolic parameters including pH, glucose, and lactate levels were evaluated, while assessment of their hemostatic capacity was performed using light transmission aggregometry (LTA) and viscoelastic studies such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG). Last, Annexin V levels were measured though flow cytometry for evaluation of platelet activation. Clot strength, as reflected by the maximum clot firmness (MCF) and the maximum amplitude (MA) parameters of the viscoelastic studies was significantly decreased in the PRT-treated platelets compared to the control platelets (p<0.05). Clot strength based on MCF and MA values was also found to be decreasing over storage time in PRT-treated platelets (p<0.001), while this was not evident in control platelets. Moreover, the comparison between pH, glucose, and lactate levels were indicative of increased metabolic activity in PRT-treated platelets compared to control platelets (p<0.001). Last, Annexin-V was significantly higher in PRT-treated platelets compared to control platelets on the 7th day of the storage period (p<0.001). The results of this study indicate that increased PSL induced by PRT treatment leads to a decreased in vitro platelet hemostatic efficacy and increased metabolic activity. However, the clinical impact of these alterations needs further investigation.

Transfusion outcomes between regular and low yield pathogen reduced platelets across different patient populations in a single institution.

Pathogen reduction technology (PRT) effectively mitigates bacterial contamination in platelets but is more likely to produce low yield units. Although low dose transfusion using conventional platelets has not been associated with increased bleeding, these findings have not been reproduced with PRT-treated platelets. Platelet transfusions in a tertiary adult hospital were retrospectively reviewed. Comparisons were made between PRT-treated regular (PRT-PR) and low (PRT-PL) yield platelets. Outcomes examined included the number of platelets and RBCs transfused, transfusion-free interval, and corrected count increment (CCI). Subgroup analyses were also performed on hematology-oncology inpatients and outpatients, as well as non-hematology-oncology patients. Platelet utilization per patient remained mostly unchanged (mean 2.9-4.3units per patient per month) even when the frequency of PRT-PL transfusion increased. Among 1402 patients examined, the number of platelets and RBCs transfused was not significantly different between patients first transfused with PRT-PR versus PRT-PL (mean number of platelet units=2.8 vs. 3.1, p=0.38; mean number of RBC units=4.8 vs. 4.3, p=0.93). Among 10,257 platelet transfusions examined, the transfusion-free interval (hazard ratio=1.05, 95% confidence interval 1.00-1.10) and CCI (10.2 vs. 11.0, p=0.70) were comparable between PRT-PR and PRT-PL units. Similar findings were observed in all subgroups, except for shortened transfusion-free intervals among hematology-oncology inpatients. PRT-PR and PRT-PL units may be used in an equivalent manner to maintain an adequate platelet inventory, since there was only a minor difference in time between transfusions.

Transfusion-associated adverse events and implementation of blood safety measures - findings from the 2017 National Blood Collection and Utilization Survey.

Serious transfusion-associated adverse events are rare in the United States. To enhance blood safety, various measures have been developed. With use of data from the 2017 National Blood Collection and Utilization Survey (NBCUS), we describe the rate of transfusion-associated adverse events and the implementation of specific blood safety measures. Data from the 2017 NBCUS were used with comparison to already published estimates from 2015. Survey weighting and imputation were used to obtain national estimates of transfusion-associated adverse events, and the number of units treated with pathogen reduction technology (PRT), screened for Babesia, and leukoreduced. The rate of transfusion-associated adverse events requiring any diagnostic or therapeutic interventions was stable (275 reactions per 100,000 transfusions in 2015 and 282 reactions per 100,000 transfusions in 2017). In 2017 among US blood collection centers, 16 of 141 (11.3%) reported screening units for Babesia and 28 of 144 (19.4%) reported PRT implementation; 138 of 2279 (6.1%) hospitals reported transfusing PRT-treated platelets. In 2017, 134 of 2336 (5.7%) hospitals reported performing secondary bacterial testing of platelets (50,922 culture-based and 63,220 rapid immunoassay tests); in 2015, 71 of 1877 (3.8%) hospitals performed secondary testing (87,155 culture-based and 21,779 rapid immunoassay tests). Nearly all whole blood/red blood cell units and platelet units were leukoreduced. Besides leukoreduction, implementation of most blood safety measures reported in this study remains low. Nationally, hospitals might be shifting from culture-based secondary bacterial testing to rapid immunoassays.

Platelets treated with pathogen reduction technology: current status and future direction.

Allogeneic platelets collected for transfusion treated with pathogen reduction technology (PRT), which has been available in some countries for more than a decade, are now increasingly available in the United States (US). The implementation of PRT-treated platelets, also known as pathogen-reduced platelets (PRPs), has been spurred by the need to further decrease the risk of sepsis associated with bacterial contamination coupled with the potential of this technology to reduce the risk of infections due to already recognized, new, and emerging infectious agents. This article will review available PRP products, examine their benefits, highlight unresolved questions surrounding this technology, and summarize pivotal research studies that have compared transfusion outcomes (largely in adult patients) for PRPs with non-PRT-treated conventional platelets (CPs). In addition, studies describing the use of PRPs in pediatric patients and work done on the association between PRPs and HLA alloimmunization are discussed. As new data emerge, it is critical to re-evaluate the risks and benefits of existing PRPs and newer technologies and reassess the financial implications of adopting PRPs to guide our decision-making process for the implementation of transfusing PRPs.

Effects of Apheresis Platelets Treated with Vitamin B2 Photochemical Technology on the Release of White Blood Cells- and Platelet-Derived Cytokines during Storage

To investigate whether vitamin B2 photochemical pathogen reduction technology(PRT) treatment may lead to increase white cell- and platelet- derived cytokines release from platelets during storage. Sixty milliliters of leukodepleted apheresis platelets were collected from 20 healthy donors, then were divided into 2 parts: one part (30 ml) remained untreated to serve as control, while the other part was treated with vitamin B2-UVB photo-chemical technology as experimental group. During 7 d of storage under standard blood bank conditions, platelet coun-ting (PC), platelet distribution width (PDW), mean platelet volume (MPV), white cell-derived cytokines (IL-1β, IL-2, IL-6, IL-8, TNF-α and IFN-γ) and platelet-derived cytokines (CCL3, CCL5, TGF-β-1 and PF4), P-selectin and phosphatidyl serine (PS) were analyzed on day 1, 3, 5 and 7 of storage, respectively. No signi-ficant differences were observed on PC, PDW and MPV between the experimental and control groups, respectively. The higher levels of platelet-derived cytokines were detected and reached a plateau after 5-7 days of storage, and the cyto-kines showed significant increase in experimental group compared with the control group. PS expression increased signi-ficantly in experimental group as compared with control group on day 3, 5 and 7 of storage, respectively. The accumula-tion of P-selectin was significant higher in experimental group than that in control group on day 5 and 7 of storage (P<0.05). The white cell-derived cytokines were not elevated by PRT treatment during 7 days of storage. The PRT-treated platelets are the main source of released cytokines during storage of PRT treatment. The levels of platelet-derived cytokines reach a plateau after 5-7 days of storage, most likely due to accelerated platelet activation and apoptosis.

Evaluation of the post-transfusion platelet increment and safety of riboflavin-based pathogen reduction technology (PRT) treated platelet products stored in platelet additive solution for 5 days or less versus 6–7 days

Background and ObjectivesPlatelets are stored routinely for 5 days or less and extended platelet storage time could improve product availability. This study compared platelet count increments (CI24hs) of riboflavin plus UV-light (PRT) treated platelet products in platelet additive solution stored for 5 days or less to products stored for 6–7 days. Material and MethodsThis was a retrospective study comparing CI24hs between two groups. Hematology patients received PRT treated platelet products stored for <5 days, or for 6–7 days. Platelet counts and adverse events during and up to 24 hours after transfusion were recorded and compared between the groups. ResultsNinety-seven patients received 168 transfusions of <5 day old PRT-treated platelets and 49 patients received 74 transfusions of 6–7 day old PRT-treated platelets.There was no statistically significant difference in CI24hs between the <5 day (median 6000) and 6–7 day storage group (median 8000) (p-value = 0.509). One mild fever was documented in the <5 day storage group. ConclusionCI24hs are similar for PRT-treated PLTs stored in PAS for <5 or 6–7 days. Studies to further evaluate clinical outcomes such as bleeding are ongoing.

Transfusion of Human Platelets Treated with Mirasol Pathogen Reduction Technology Does Not Induce Acute Lung Injury in Mice.

Pathogen reduction technology (PRT) has been developed in an effort to make the blood supply safer, but there is controversy as to whether it may induce structural or functional changes to platelets that could lead to acute lung injury after transfusion. In this study, we used a commercial PRT system to treat human platelets that were then transfused into immunodeficient mice, and the development of acute lung injury was determined. P-selectin expression was higher in the Mirasol PRT-treated platelets compared to control platelets on storage day 5, but not storage day 1. Transfusion of control vs. Mirasol PRT-treated platelets (day 5 of storage, 109 platelets per mouse) into NOD/SCID mice did not result in lung injury, however transfusion of storage day 5 platelets treated with thrombin receptor-activating peptide increased both extravascular lung water and lung vascular permeability. Transfusion of day 1 platelets did not produce lung injury in any group, and LPS priming 24 hours before transfusion had no effect on lung injury. In a model of transfusion-related acute lung injury, NOD/SCID mice were susceptible to acute lung injury when challenged with H-2Kd monoclonal antibody vs. isotype control antibody. Using lung intravital microscopy, we did not detect a difference in the dynamic retention of platelets in the lung circulation in control vs. Mirasol PRT-treated groups. In conclusion, Mirasol PRT produced an increase in P-selectin expression that is storage-dependent, but transfusion of human platelets treated with Mirasol PRT into immunodeficient mice did not result in greater platelet retention in the lungs or the development of acute lung injury.

Impact of Pathogen Reduction Technology Treatment and Storage in New Generation Platelet Additive Solutions (PAS) on Platelet Function.

Abstract 2115Poster Board II-92New strategies for preparing platelet concentrates (PCs) are investigating the combination of pathogen reduction technologies (PRT) with storage of platelets in additive solutions (PAS) containing phosphate buffer. While these approaches have several advantages by reducing adverse effects, improving biological safety and increasing plasma availability, there is a reasonable concern on how these strategies could affect platelet function. In the present study we have evaluated the effect of Marisol® PRT treatment (CaridianBCT Biotechnologies, LLC) in combination with storage in PAS-III (Intersol; Baxter Healthcare Corp) or PAS-IIIM (SSP+; MacoPharma) on analytical and functional characteristics of apheresis PCS.PCs (2.5-3.4×109plts/ml) were split into three aliquots. One was kept untreated and stored in plasma as a control (CON-PPP). One was PRT-treated and stored in the corresponding PAS (PRT-PASIII or PRT-IIIM) with a 35% plasma carryover to achieve a final concentration of 0.7-1.5 × 109 plt/ml. The last aliquot was stored in the corresponding PAS (CON-PASIII or CON-PASIIIM), not subjected to PRT treatment. PCs were stored under standardized conditions and evaluations were performed on days 0, 5 and 7. Cell quality parameters (pH, swirl, lactate and glucose), flow cytometry analysis of major platelet glycoproteins and activation dependent antigens were assessed. Adhesive and aggregating functions of platelets were evaluated using an ex vivo perfusion model with flowing reconstituted blood recirculating through damaged vascular segments.A slight reduction in platelet counts was noticed on day 7 compared to day 0 in PRT-treated PCs (p<0.05), however no statistical differences were observed between the different study groups. All measured cell quality parameters were within ranges previously published. Flow cytometry analysis revealed comparable levels of the analyzed glycoproteins for all conditions evaluated. Only moderate reductions in the expression of GPIb were observed on day 7 of storage in all groups except for CON-PASIIIM. A progressive increase in the expression of P-selectin was observed in both controls and PRT-treated PCs during storage. Lysosomal integral membrane protein (LIMP) expression was increased in PRT-PASIII and PRT-PASIIIM and CON-PASIII, but not CON-PASIIIM PCs. PRT-PASIII PCs showed the highest levels of annexin V binding after 7 days of storage. Studies under flow conditions showed comparable levels of adhesion and aggregation to subendothelium for PRT-treated platelets stored in PAS solutions at 5 days of storage. A detailed morphometric analysis revealed slightly enhanced adhesive functions in CON-PASIII on day 0 and moderate reductions in adhesive properties in PRT-PASIII, but not PRT-PASIIIM PCs after 7 days of storage.Our investigations show that cell quality parameters, glycoproteins levels and platelet functions were preserved in PRT-treated concentrates and stored in new generation PAS for up to 5 days. The relevance of our experimental data on the in vivo performance of PCs exposed to PRT and stored in new generation PAS deserve further investigation in the clinical setting. Disclosures:Escolar:Caridian BCT Technologies: Consultancy, Research Funding. Marschner:Caridian BCT Technologies: Employment. Goodrich:Caridian BCT Technologies: Employment. Galan:Caridian BCT Technologies: Research Funding.