Letters to the Editor
4
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article. Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest: Employment or Leadership: None declared. Consultant or Advisory Role: None declared. Stock Ownership: None declared. Honoraria: None declared. Research Funding: H.L. Jørgensen, Danish Biotechnology Centre for Cellular Communication; H.P. Sennels, Danish Biotechnology Centre for Cellular Communication; J. Fahrenkrug, Danish Biotechnology Centre for Cellular Communication. Expert Testimony: None declared.
References 1. Goetze JP. Biosynthesis of cardiac natriuretic peptides. Results Probl Cell Differ 2010;50: 97–120. 2. Goetze JP, Georg B, Jørgensen HL, Fahrenkrug J. Chamber-dependent circadian expression of cardiac natriuretic peptides. Regul Pept 2010; 160:140 –5. 3. Sennels HP, Jørgensen HL, Hansen ALS, Goetze JP, Fahrenkrug J. Diurnal variation of hematology parameters in healthy young males. Scand J Clin Lab Invest 2011;71:532– 41. 4. Morgenthaler NG, Struck J, Thomas B, Bergmann A. Immunoluminometric assay for the midregion of pro-atrial natriuretic peptide in human plasma. Clin Chem 2004;50:234 – 6. 5. Hunter I, Rehfeld JF, Goetze JP. Measurement of the total proANP product in mammals by processing independent analysis. J Immunol Methods 2011;370:104 –10. 6. Kanabrocki EL, Sothern RB, Scheving LE, Halberg F, Pauly JE, Greco J, et al. Ten-year-replicated circadian profiles for 36 physiological, serological and urinary variables in healthy men. Chronobiol Int 1988;5:237– 84.
Jens P. Goetze3* Henrik L. Jørgensen4 Henriette P. Sennels4 Jan Fahrenkrug4 3
Department of Clinical Biochemistry Rigshospitalet, University of Copenhagen
792 Clinical Chemistry 58:4 (2012)
Copenhagen, Denmark Department of Clinical Biochemistry Bispebjerg Hospital, University of Copenhagen Copenhagen, Denmark
* Address correspondence to this author at: Department of Clinical Biochemistry KB 3014, Rigshospitalet 9 Blegdamsvej, DK-2100 Copenhagen, Denmark Fax ⫹45-3545-2880 E-mail:
[email protected] Previously published online at DOI: 10.1373/clinchem.2011.178921
Assessing Pneumatic Tube Systems with Patient-Specific Populations and LaboratoryDerived Criteria To the Editor: The October 2011 issue of Clinical Chemistry highlights the importance of monitoring pneumatic tube systems (PTSs) to control preanalytical factors that may affect laboratory results (1, 2 ). Two important themes emerge: (a) the possible requirement of morefrequent monitoring if the PTS produces changes in the 3-axis acceleration (i.e., forces) and (b) consideration for specific populations of patients (i.e., hematology and/or oncology patients) whose blood samples may be more susceptible to PTS. As Felder noted, the work by Streichert et al. may usher in a new practice for monitoring PTS by means of data loggers (1, 2 ); however, in the interim, laboratories will be required to monitor PTSs with split-sample testing. In this regard, the number of studies and approaches that have assessed the impact of PTSs on the quality of samples has been surprisingly limited (3 ). Moreover, the available guidelines have mainly suggested that PTSs be evaluated and
that certain analytes may be affected by the automated system (e.g., lactate dehydrogenase), whereas others (e.g., aspartate aminotransferase) may not (4 ). Additional questions arising from the study of Streichert et al. are whether samples from healthy volunteers are the most appropriate to test in PTSs and what criteria should be used to evaluate the acceptability of samples subjected to PTSs. While implementing a new PTS in our hospital, we wanted to determine if patient-specific attributes and laboratory-defined criteria could be used to assess the performance of the new PTS. Given that patients may be relocated to different hospital locations/wards, one of our goals was to evaluate the new PTS by using available leftover blood samples in the core laboratory that had been obtained from the different locations. For this evaluation, we randomly selected and resuspended lithium heparin blood samples (4-mL green-top Vacutainers; BD) from 5 different patients in each of 4 different hospital locations: the emergency department, the intensive care unit, surgical oncology and orthopedics, and hematology/ oncology. We pooled samples from each location and aliquoted them uniformly (1 mL) into 5 tubes (groups A–E) that were to be sent from the same station (the hematology/oncology ward) via PTS and tested with different interventions. The groups were as follows: group A, control (no PTS); group B, PTS (no intervention); group C, PTS and foam liner in tube only; group D, PTS and no foam, but tube caught at end destination without impact; and group E, PTS and foam with tube caught at end destination. The analytes chosen for this experiment were those that Streichert et al. found to produce different results when the PTS was used (potassium, lactate dehydrogenase, aspartate aminotransfer-
Letters to the Editor
Table 1. Assessing different interventions within the PTS according to different comparability criteria.
Patient pools
Intervention groupa
Mean
Difference from control (group A, no PTS)
Percentage difference from control group
Within laboratorydefined differenceb
Within critical difference (CLSI)
Within biological variation (CVi)
Potassium, mmol/L Emergency department
Intensive care unit
Hematology/oncology
Surgical and orthopedics
Lactate dehydrogenase, U/L Emergency department
Intensive care unit
Hematology/oncology
Surgical and orthopedics
A
3.615
B
3.615
0.00
0.00%
Yes
Yes
Yes
C
3.635
0.020
0.55%
Yes
Yes
Yes
D
3.680
0.065
1.80%
Yes
Yes
Yes
E
3.705
0.090
2.49%
Yes
Yes
Yes
A
3.290
B
3.365
0.075
2.28%
Yes
Yes
Yes
C
3.340
0.050
1.52%
Yes
Yes
Yes
D
3.515
0.225
6.84%
No
No
No
E
3.365
0.075
2.28%
Yes
Yes
Yes No
A
4.455
B
5.195
0.740
16.61%
No
No
C
4.935
0.480
10.79%
No
No
No
D
4.825
0.370
8.31%
No
No
No
E
4.625
0.170
3.82%
No
Yes
Yes
A
3.890
B
3.960
0.070
1.80%
Yes
Yes
Yes
C
4.010
0.120
3.08%
Yes
Yes
Yes
D
4.050
0.160
4.11%
No
Yes
Yes
E
3.990
0.100
2.57%
Yes
Yes
Yes
96.0 50.00 154.0 34.50
37.94% 19.76% 60.87% 13.64%
No No No No
No No No No
No No No No
26.00 15.50 99.50 32.50
5.17% 3.08% 19.78% 6.46%
Yes Yes No Yes
No Yes No No
Yes Yes No Yes
198.5 117.5 136.5 49.5
36.59% 21.66% 25.16% 9.12%
No No No No
No No No No
No No No No
161.50 45.50 49.00 64.00
87.30% 24.59% 26.49% 34.59%
No No No No
No No No No
No No No No
A B C D E A B C D E
253.0 349.0 303.0 407.0 287.5 503.0 529.0 518.5 602.5 535.5
A B C D E A B C D E
542.5 741.0 660.0 679.0 592.0 185.0 346.5 230.5 234.0 249.0
Continued on page 794
Clinical Chemistry 58:4 (2012) 793
Letters to the Editor
Table 1. Assessing different interventions within the PTS according to different comparability criteria. (Continued from page 793)
Patient pools
Aspartate aminotransferase, U/L Emergency department
Intensive care unit
Hematology/oncology
Surgical and orthopedics
Phosphate, mmol/Lc Emergency department
Intensive care unit
Hematology/oncology
Surgical and orthopedics
Intervention groupa
Mean
A B C D E A B C D E A B C D E A B C D E
32.40 36.05 34.10 32.60 35.95 32.25 32.50 32.25 34.35 31.05 69.65 92.25 82.90 81.50 75.35 28.45 29.90 29.60 28.10 30.55
A B C D E A B C D E A B C D E A B C D E
a
0.805 0.810 0.805 0.815 0.795 1.140 1.135 1.120 1.190 1.130 1.140 1.205 1.135 1.160 1.130 0.790 0.795 0.800 0.805 0.785
Difference from control (group A, no PTS)
Percentage difference from control group
Within laboratorydefined differenceb
Within critical difference (CLSI)
Within biological variation (CVi)
3.65 1.70 0.20 3.55
11.27% 5.25% 0.62% 10.96%
Yes Yes Yes Yes
Yes Yes Yes Yes
Yes Yes Yes Yes
0.25 0.00 2.10 ⫺1.20
0.78% 0.00% 6.51% ⫺3.72%
Yes Yes Yes Yes
Yes Yes Yes Yes
Yes Yes Yes Yes
22.60 13.25 11.85 5.70
32.45% 19.02% 17.01% 8.18%
No Yes Yes Yes
No No No Yes
No No No Yes
1.45 1.15 ⫺0.35 2.10
5.10% 4.04% ⫺1.23% 7.38%
Yes Yes Yes Yes
Yes Yes Yes Yes
Yes Yes Yes Yes
0.005 0.000 0.010 ⫺0.010
0.62% 0.00% 1.24% ⫺1.24%
Yes Yes Yes Yes
Yes Yes Yes Yes
Yes Yes Yes Yes
⫺0.005 ⫺0.020 0.050 ⫺0.010
⫺0.44% ⫺1.75% 4.39% ⫺0.88%
Yes Yes Yes Yes
Yes Yes Yes Yes
Yes Yes Yes Yes
0.065 ⫺0.005 0.020 ⫺0.010
5.70% ⫺0.44% 1.75% ⫺0.88%
Yes Yes Yes Yes
Yes Yes Yes Yes
Yes Yes Yes Yes
0.005 0.010 0.015 ⫺0.005
0.63% 1.27% 1.90% ⫺0.63%
Yes Yes Yes Yes
Yes Yes Yes Yes
Yes Yes Yes Yes
Group A, control (no PTS); group B, PTS (no intervention); group C, PTS and foam liner in tube only; group D, PTS and no foam, but tube caught at end destination without impact; group E, PTS and foam with tube caught at end destination. b Potassium criteria: acceptable laboratory-defined difference, ⱕ3%; critical difference (CLSI), ⱕ4%; biological variation (CVi), ⱕ4.8%. Lactate dehydrogenase criteria: acceptable laboratory-defined difference, ⱕ8%; critical difference (CLSI), ⱕ4%; CVi, ⱕ8.6%. Aspartate aminotransferase criteria: acceptable laboratorydefined difference, ⱕ21%; critical difference (CLSI), ⱕ13%; CVi, ⱕ11.9%. Phosphate criteria: acceptable laboratory-defined difference, ⱕ6%; critical difference (CLSI), ⱕ9%; CVi, ⱕ8.5%. c Factor for converting phosphate concentration in SI units to conventional units: 1 mmol/L ⫽ 3.10 mg/dL.
794 Clinical Chemistry 58:4 (2012)
Letters to the Editor ase, phosphate), on the basis of the allowed relative deviation of QCs as specified by the German Federal Medical Council (2 ). An alternative approach, however, may be to use acceptable comparability testing for instruments within a single laboratory (5 ). In brief, comparability testing (i.e., instrument-toinstrument comparison) is a component of the quality-assurance process and may indicate that a measurement procedure needs to be reviewed for possible corrective action. One can assess comparability testing in various ways [CLSI C54 –1 guideline, or biological variation (CVi)], and we have recently established our own laboratory-defined acceptable percentage differences (Table 1) (5 ). Samples from groups B–E were sent via PTS within a 20-min period, and all samples (groups A–E) were centrifuged together and analyzed in duplicate on the Roche P Modular System (overall CVs used for critical difference were 1% for potassium, 1% for lactate dehydrogenase, 3% for aspartate aminotransferase, and 2% for phosphate). The percentage differences in the mean analyte measurements between group A (control) and the different interventions were then assessed according to the different comparability criteria (Table 1). From these data, differences between the patient pools were seen, with the hematology/ oncology pool being more affected by the PTS than the intensive care unit pool (56% of the hematology/ oncology pool results and 13% of the intensive care unit pool results exceeded laboratory-defined limits; P ⫽ 0.023). Moreover, it was evident that group E (foam liner and tube caught) had the least amount of cellular disruption, as indicated by both the potassium and aspartate aminotransferase re-
sults for the hematology/oncology pool. These investigations and dialogue with physicians led to further vendor modifications of the PTS with respect to both the impact and the speed of tubes during transit. These adjustments were made before any patient samples intended for clinical reporting were sent via the system. This approach of assembling different pools representative of different patient groups within a hospital may be useful for quickly ascertaining the suitability of PTS transport for chemistry testing and may be an option for monitoring PTSs after their initial validation. Furthermore, either laboratory-defined or guidelinedriven criteria for comparability testing may be used to assess whether observed differences attributable to PTS transport are acceptable. Frequent testing, assessing the volume of blood in tubes (e.g., full vs partial blood draw), and use of an increased number of samples and multiple runs over several days (i.e., dayto-day variation) of PTS operation would provide additional criteria for assessing PTS performance. In summary, PTS may shorten the time for sample transport to the clinical laboratory; however, monitoring is required to ensure that laboratory results from blood samples transported by PTS are still accurate.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors’ Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
References 1. Felder RA. Preanalytical errors introduced by sample-transportation systems: a means to assess them. Clin Chem 2011;57:1349 –50. 2. Streichert T, Otto B, Schnabel C, Nordholt G, Haddad M, Maric M, et al. Determination of hemolysis thresholds by the use of data loggers in pneumatic tube systems. Clin Chem 2011;57:1390 –7. 3. Plebani M, Zaninotto M. Pneumatic tube delivery systems for patient samples: evidence of quality and quality of evidence. Clin Chem Lab Med 2011;49:1245– 6. 4. CLSI. Procedures for the handling and processing of blood specimens for common laboratory tests; approved guideline—fourth edition. CLSI document H18 –A4. Wayne (PA): CLSI; 2010. p 11–2. 5. Mansour M, Wang L, Clark L, Kavsak P. An approach for comparability testing of 20 core clinical chemistry analytes measured between identical Roche P-modular platforms [Abstract]. Clin Biochem 2011;44:1175– 6.
Peter A. Kavsak1,2* Maged Mansour1 Li Wang1 Sara Campeau2 Lorna Clark2 Dan Brooks2 Mike Trus1,2 1
Department of Pathology and Molecular Medicine McMaster University Hamilton, Ontario, Canada 2 Juravinski Hospital and Cancer Centre Hamilton, Ontario, Canada * Address correspondence to this author at: Discipline of Clinical Chemistry/Immunology Hamilton Regional Laboratory Medicine Program Juravinski Hospital and Cancer Centre (Core Lab Section) 711 Concession St. Hamilton, Ontario, L8V 1C3 Canada Fax 905-575-2581 E-mail
[email protected] Previously published online at DOI: 10.1373/clinchem.2011.179044
Clinical Chemistry 58:4 (2012) 795
