Achieving the advantages of Plasma: How to prepare to convert to Plasma, the experience and perspective of a European hospital

Transcription

1 Preanalytical Education Series Achieving the advantages of Plasma: How to prepare to convert to Plasma, the experience and perspective of a European hospital Prof. Tim James

2 Prof. Tim James, Laboratory Manager & Head Biomedical Scientist Oxford University Hospitals NHS Foundation Trust The Oxford University Hospital has been using plasma for its biochemistry testing for several years. Responsibilities, includes management of biochemistry services at three laboratory sites. His current research interests are broad and cover many aspects of Clinical Biochemistry, but particularly improving the quality of diagnostic services. He has collaborated with many clinical teams including those in primary care, intensive care, transplantation and endocrinology. He has published articles, written book chapters and made many presentations at international seminars on diabetes mellitus, renal disease and wound healing, the application of automation within clinical laboratories. He is an avid supporter of the use of plasma for clinical chemistry testing

3 Overview When a laboratory is considering switching to plasma for clinical chemistry testing, it is important that there is effective communication and consideration for all impacted processes and personnel. This talk will define some of the key impacts and provide a personal prospective on the implementation in one major EU hospital.

4 Are you considering switching to plasma? a) No b) Possibly c) Yes for stat/emergency testing only d) Yes for all tests Tell us what you think...

5 Oxford University Hospitals John Radcliffe Hospital Horton General Hospital Churchill Hospital Nuffield Orthopaedic Centre

6 During million patient contacts 108,000 planned admissions 90,000 emergency admissions 130,000 emergency department attendances 1,300 beds, including 100 for children 67 wards 44 operating theatres 11,598 staff 1,800 doctors 3,600 nurses 1,300 healthcare support workers

7 Laboratories On three sites Main laboratory at the John Radcliffe Hospital Core Automated Laboratory, multidisciplinary 7.5 million tests per year Chemistry Providing around 99% of laboratory testing in Oxfordshire - catchment of 800,000 residents 50% of work from primary care

8 Core Automated laboratory

9 Key Statistics 5,500 to 6000 tubes/day on Track 50% inpatient, 50% General practice Around 200 specimens from Emergency Department (JR & HH) >80% of all Biochemistry tests are performed on lithium heparin plasma with gel

10 What are your biggest concerns about implementing plasma? a) Need to change reference ranges b) Ability to run all of your analytes in plasma c) Need to validate new methods? d) How to communicate any changes to the clinicians? e) Changes to your IT systems, eg LIS or electronic order placement f) Other Tell us what you think...

11 Pressure Points Right result, every time In difficult samples From a variety of patients Across a wide range of locations Quickly Cost effectively

12 The Oxford Experience 30 years experience of using Lithium Heparin plasma (currently PST II) as a preferred sample type for: All routine Biochemistry (except lithium) All thyroid function tests Most therapeutics Serum for some hormones, troponin, BetaHCG etc

13 The Oxford Experience Is Oxford typical of UK labs? No - most UK Labs use serum as the primary clinical chemistry tube type

14 A Longstanding UK Debate: ACB Mailbase Serum vs Plasma

15 How common is plasma tube usage in Europe?

16 Why did Oxford start using plasma? 1980 s thought processes: Need to standardize Mixture of serum and plasma being used interchangeably Known differences between the two specimen types To minimise pre-analytical variability only one type was desired Single reference range based on a single tube type Why plasma?

17 Why did Oxford start using plasma? Why plasma: No delay required for centrifugation step Better volume yield - benefit for paediatrics Better quality of specimen for potassium most frequently requested test in most chemistry laboratories

18 Plasma - Rationale Faster TAT clotting time not needed Reduces potential for in vitro effects Potassium, phosphate release from cells ^platelets, polycythaemia, leukaemias Fragile red cells Higher plasma yield paediatric samples

19 Considerations When Introducing Plasma Workload, stock, storage labour/staffing, Time, Cost of validation LIS, Middleware, Hospital Software, Automation, FEA, Centrifuges Reception area, Transportation, aliquoting, labelling, request forms Primary vs secondary tubes Reference Ranges, Flags, Cut offs, Comments, Lab manual, Lab SOPs, Maintenance STAT vs Routine workflow Training (e-learning Tool) Logs

20 Workflow effects at the point of collection: Who is taking the blood? Access to the person taking blood samples can be challenging Blood collection guides widely distributed as poster and pocket guides Global s Auditing of training & blood collection Hospital Based Phlebotomists Junior medical staff Induction time Community Based GP practice manager Lead nurses and practice phlebotomist

21 Workflow effects in clinical requesting Electronic requesting systems: Use defined tube types for all tests on the system In a transition these would need to be redefined May be seen as an opportunity to review all defined fields on the system including sample volume (Note this could contribute as evidence for the periodic assessment of sample volume required for ISO 15189) In Oxford two different systems in use one in general practice and one in the hospital based locations

22 Workflow effects in Reception No checking of clotting No fibrin masses post centrifugation

23 Workflow effects with LIMS LIMs changes: As with the electronic systems this would need to define which tests could be undertaken on which tube type to enable appropriate netting Specimen reception staff would require training of the new requiements Lab number changes currently we use root numbers for chemistry which are C123456x = Lith hep plasma GC123456x = Fluoride oxalate plasma SC = Serum H = EDTA whole blood CH = Citrate plasma

24 Workflow effects on lab automation Automation impact: Redefine the test : tube association Might lead to more tubes on the system Irrespective of the change required each tube needs a unique identifier No requirement to change instrument settings No extra maintenance required/consult manufacturer Impact on stability on automated storage units studies look reasonable for plasma Cap colour recognition system against a test mapping Centrifugation conditions Auto-aliquoter

25 Work flow effects Post Analytically Sample stability How you store the sample possibly aliquoting Do you need to do any post storage processing Transportation

26 Do you have different ref ranges for serum or plasma? a) We are not running plasma b) We use the same reference range c) We use different reference ranges Tell us what you think...

27 Did we undertake any reference range studies? Yes core analytes in plasma were analysed on an American Monitor Parallel Date formed the basis for our reference intervals Published as an appendix in the Oxford Textbook of Medicine during the 1980 s and 1990 s I still have the data in a file in my office Analyser changes have occurred every 8 to 10 years so it has been necessary to repeat reference range assessments periodically Hold a bank of aliquoted samples of paired plasma and serum from volunteers currently have about 200 samples for adults 20 to 65 years equal male and female Precious resource so we only use these when there is noted methodological shift or some ambiguity Also data-mine samples processed (For an approach to this see Shine BS. Ann Clin Biochem. 2008;45: ) There are always opportunities do undertake further refinements in reference ranges

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29 Did we communicate reference range changes to clinicians? Yes No single technique is perfect Global message to users (one for primary care and one to all hospital staff) Comments added to reports for 6 months stating a change of range with the associated date All reports are transmitted with the appropriate range applied within the message

30 What guidelines or reference do you use when establishing reference ranges? a) Analyte product insert b) CLSI C28-A3. Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory c) IFCC Recommendations on the Estimation of Reference Intervals d) Internal procedure e) Other Tell us what you think...

31 Verification or Validation? What do you need to consider See CLSI guideline ISO Non-standard methods Lab designed or developed methods Standard methods outside their scope of use Validated methods subsequently modified

32 How to manage dual acceptance of plasma or serum? Options might be: Wider reference intervals Dual ranges, difference test codes more complex processes

33 Where do we notice differences Potassium Phosphate Glucose Alkaline Phosphatase

34 Potassium Well documented in the scientific literature Potassium released from cells during the clotting process pseudohyperkalaemia Particularly problematic in patients with high platelet counts, essential polycythaemia, fragile red cells etc.

35 Phosphate Well described difference in phosphate for plasma vs serum To overcome this in-house derived reference intervals Healthy volunteers often lab staff (healthy?!) Clinical Trials Blood donors NHS Blood Transfusion Service Age specific reference intervals Adult range = mmol/l

36 Glucose Fluoride oxalate as reference point However many labs use lith hep plasma or serum glucose need to redefine the exact details of testing times

37 Alkaline Phosphatase 15 years ago Horton and JR hospitals underwent merger Historically Horton used serum for Chemistry analytes. Retrospective comparison between ALP patient results: 62,809 ALP results from JR, 10,285 from HH Same platform, DEA buffered PNPP method The 95 th centile values for ALP on the site using serum were 10% above the reference range; values on JR site equated to the reference interval (adult RR IU/L, in-house). Paired specimens take from 51 patients - Deming regression showed: SST ALP = 1.10 [PST ALP] -5.5

38 Challenges - Hormones Lithium heparin plasma often not validated by immunoassay manufacturers for hormone assays?mechanism of interference: Potential causes: Robustness of the immunoassay reaction Interference from sample collection device, anticoagulant, separation media etc. Sample clotting due to handling or patient condition Other? Note that the same assay from a different manufacturer may perform differently

39 Thyroid function tests Most commonly requested hormone test Frequently requested in conjunction with routine Chemistry Aim for commonality of sample types Assessed suitability of lithium heparin plasma for TSH, ft4 and ft3

40 Conclusion: No significant difference between SST II and PST II tubes for TSH, ft3 and ft4 measurements

41 Challenges ISO 15189: Any deviation from manufacturer s intended use requires full method validation Some immunoassay methods are validated by manufacturers for serum only FDA approval, costly, time-consuming etc.?analyte stability literature reports, in-house studies, departmental policy for retrospective requests use of separator gel allows stability for most analytes, information form tube supplier

42 Conclusions 30 years of experience using lithium heparin plasma as the preferred sample type for routine Chemistry and thyroid function testing Advantages over serum faster TAT, increased sample volume, more reliable potassium results Challenges ALP, Phosphate but these can be overcome: In-house reference intervals Some hormones: serum perhaps not suitable, however high volume thyroid function testing has been validated. Practical challenges revolve around: Electronic system set up HIS, LIS and automation systems Communication to users

43 Thanks Stephen Church at BD Diagnostics for inviting me to present this Webinar Oxford University Hospitals Predecessors and mentors John McVittie and Jonathan Kay All current colleagues but particularly Brian Shine who guides us all as Head of department and our statistical guru; Zoe Maunsell-Browne who has been developing our recent thoughts on plasma and serum