Development of a Quality Monitoring Program for Platelet Components: a Report of the first Four Years’ Experience At
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ORIGINAL ARTICLE Development of a quality monitoring program for platelet components: a report of the first four years’ experience at Canadian Blood Services_3402 1..9 Elena Levin, Craig Jenkins, Brankica Culibrk, Maria I.C. Gyöngyössy-Issa, Katherine Serrano, and Dana V. Devine ormal biologic differences among donors BACKGROUND: A quality monitoring program (QMP) mean that a degree of variation is inherent in for platelet concentrates (PCs) was implemented at blood components produced for transfusion.1 Canadian Blood Services (CBS) to improve standards Despite this, blood product providers strive to and to better understand platelet (PLT) products by Ngenerate components that are of high quality and are supplementing routine quality control (QC). optimally standardized to guarantee safety and effective- STUDY DESIGN AND METHODS: Annual surveys of ness.2,3 Quality control (QC) of components prepared from PCs from CBS production sites were conducted, with whole blood donations occurs at expiry and focuses on four completed to date (QMP Cycles 1-4) spanning two the product’s safety and compliance with regulatory stan- different PC production methods: PLT-rich plasma dards. For platelet concentrates (PCs), standards include (PRP) and buffy coat (BC). Randomly selected PCs pH, platelet (PLT) count per unit, sterility, and residual were sent to a central laboratory and tested 1 day after white blood cell count if the product is leukoreduced,4,5 all expiry. An expanded panel of tests including CD62P of which are monitored by routine QC at Canadian Blood expression by flow cytometry, mean PLT volume, PLT Services (CBS). Although production of blood compo- count and morphology, extent of shape change, and nents for transfusion purposes has increasingly adopted a PLT metabolic parameters, were applied. pharmaceutical industry mindset, significant deviations RESULTS: QMP data on the implementation of the BC remain in both the use of QC principles and the determi- production method across CBS indicated that BC PCs nation of standards. The panel of standardized assess- have less variable in vitro quality measures than PRP ments currently in use provides general information on PCs. For the QC parameters pH and PLT count per product characteristics at expiry, but these standards have unit, the range of mean values from each site for QMP remained unmodified for decades and do not encompass 3 and 4 fell well within the range defined by regulatory standards, a first step in defining quality benchmarks for PCs. Of the extended panel of quality parameters, CD62P expression was the most sensitive indicator of ABBREVIATIONS: BC = buffy coat; CBS = Canadian Blood change and identified an issue with the implementation Services; ESC = extent of shape change; MPV = mean platelet of the BC PC production method at one site, which was volume; PC(s) = platelet concentrate(s); PRP = platelet-rich subsequently remedied. plasma; PSL = platelet storage lesion; QMP = quality monitoring CONCLUSION: A QMP was found to be useful to program; SOP(s) = standard operating procedure(s). monitor production processes across sites and high- lights best practice approaches while deepening under- From the Canadian Blood Services, UBC Centre for Blood standing of the quality of PLT products at CBS. Research, Vancouver, British Columbia, Canada; and Canadian Blood Services, Ottawa, Ontario, Canada. Address reprint requests to: Dana Devine, PhD, Canadian Blood Services, UBC Centre for Blood Research, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; e-mail: [email protected]. Received for publication May 18, 2011; revision received August 24, 2011, and accepted August 31, 2011. doi: 10.1111/j.1537-2995.2011.03402.x TRANSFUSION **;**:**-**. Volume **, ** ** TRANSFUSION 1 LEVIN ET AL. the accumulated understanding of PLT function or the or Helmer, Noblesville, IN) under standard CBS storage effects of storage on product quality.6 conditions until testing. Twelve units from each produc- Since 2005, CBS has been conducting a quality moni- tion site were analyzed per QMP cycle. To enable compari- toring program (QMP) for the assessment of its PLT prod- son among production years, the selection of tests and ucts. The QMP consists of annual surveys of PCs from CBS procedures was made at the beginning of the study and sites and, while QC tests approximately 1% of product, remained largely unchanged throughout. The test panel QMP is conducted on a smaller scale, aiming to test 12 for PLT assessment included PLT count, MPV, blood gas units from each production site per year. A major objec- and PLT metabolites, PLT activation status, and morphol- tive of this program is to improve standards and to better ogy. Extent of shape change (ESC) was included in QMP 1 understand the quality of PLTs produced by CBS by apply- and 4. ing in vitro tests beyond those used during routine QC testing. Furthermore, samples from all CBS production sites are tested via QMP, permitting examination of the Sample collection for testing implementation of new processes across the whole orga- Before sampling, the blood group, color, and appearance nization, as well as site-to-site comparisons to assess the (e.g., redness, lipemic look) of the PC as well as the site consistency of production practices across a multisite from which the component was sent were recorded. Each organization. The program was established under the PC was weighed, and its volume was calculated. PCs were research and development division of CBS as this depart- sampled aseptically through a sampling site coupler. ment has long operated as a centralized troubleshooting Twelve milliliters of PLTs was aspirated into a 20-mL facility for product issues and had an established frame- syringe using an 18-gauge needle. From this syringe, 8 mL work for conducting PLT testing. The test panel included was used for sterility testing, 3 mL was dispensed into a several of the more commonly used PLT quality measures K2EDTA vacutainer (BD, Mississauga, Ontario, Canada) for because a secondary objective of the QMP was to generate hematology analyzer counts, and the remainder was quality benchmarks for buffy coat (BC) PCs using assays transferred to a polypropylene tube and used for PLT acti- beyond the usual QC tests and to explore whether any of vation analysis and morphology scoring. A separate 1-mL these might be useful future routine QC measures. syringe, which was sealed immediately after sampling Here data from the first four annual QMP cycles are with parafilm, was used to obtain samples for PLT meta- presented. PCs were examined at a central research and bolic analysis. development laboratory using an extended panel of in vitro quality tests. PLT count per unit and pH, which are also monitored by QC, were measured, as well as PLT mor- Test panel phology, mean PLT volume (MPV), CD62P expression, and measures of PLT metabolism. Between 2005 and 2008, PLT concentration and MPV CBS changed its method of component production from PLT concentration and MPV were obtained from a K2EDTA whole blood donations, replacing the PLT-rich plasma tube using a hematology analyzer (Advia 120, Siemens, (PRP) preparation method with the BC method, which Mississauga, Ontario, Canada), and PLT count per unit (or 7 results in pooled components consisting of PLTs from four PLT yield) was calculated as described previously. donors;7 thus we present QMP data from PCs produced using both the PRP method (QMP Cycles 1 and 2) and the CD62P analysis by flow cytometry BC method (QMP Cycles 3 and 4). Flow cytometry was conducted on one flow cytometer (Coulter Epics XL-MCL, Beckman Coulter Canada, Inc., MATERIALS AND METHODS Mississauga, Ontario, Canada) for QMP 1 and 2 or another (FACS Canto II, BD) for QMP 2, 3, and 4. During the PLT preparation, shipping and test selection changeover between instruments, the BD flow cytometer PCs were prepared by either the PRP or the BC method was cross-validated against the Coulter instrument before following CBS standard operating procedures (SOPs) as QMP data collection, with samples analyzed on both described elsewhere.7 All PCs were analyzed a day after instruments and the results used to determine perfor- expiry (Day 6) in a central testing laboratory in Vancouver, mance and agreement between the two instruments British Columbia, Canada. Components were packed in (r = 0.989). Flow cytometric detection of PLT surface anti- standard CBS PLT boxes (ISC E-38), with gel packs to gens was conducted as described previously.7,8 Briefly, control temperature fluctuations and shipped overnight. PLTs were diluted with phosphate-buffered saline (PBS) to PCs were shipped either on Storage Day 2 or on Storage a concentration of 200 ¥ 109/L and stained with a fluores- Day 4 or 5 and shipping from all sites was less than 24 cent antibody cocktail containing anti-CD42-fluorescein hours in duration. PCs were stored in a 22°C PLT agitator isothiocyanate (FITC) and anti-CD62P-phycoerythrin (PE; (either Thermo Forma, Thermo Scientific, Asheville, NC; Immunotech, Marseille, France). Staining was performed 2 TRANSFUSION Volume **, ** ** QUALITY MONITORING OF PLTs in duplicate for 30 minutes, followed by fixation with 0.2% with HEPES (15 mmol/L final concentration, pH 7.0-7.4). formol saline (0.2% formaldehyde in 0.9% NaCl) and The ESC was calculated by the instrument by integrating analysis by flow cytometry. Five-thousand CD42-positive optical density readings from PLT-poor plasma and PRP in events were collected during each acquisition. Isotype the absence and presence of ADP (20 mmol/L final con- antibodies (IgG2a-FITC and IgG1-PE, Immunotech) were centration). Assays were performed at 37°C. used to control for nonspecific binding. PLTs activated with 1 U/mL bovine thrombin (gift from J. Fenton) served as a positive control. Statistical analysis Early in QMP,power calculations were conducted for each PLT morphology parameter to establish sample sizes sufficient to deter- Morphology was assessed by modified Kunicki score, as mine significant differences from the population.