Jie Gao, PhD, MLS(ASCP)CM

The clinical laboratory always seeks to improve services due to its close association to patient safety and satisfaction. However, clinical laboratory testing is a highly complex process (i.e., preanalytical phase, analytical phase, and postanalytical phase), and the frequency of laboratory errors has been reported to be 0.012-0.6 percent of all test results.1 According to a recent survey on laboratory errors, the preanalytical errors account for over 60 percent of laboratory errors.2

The preanalytical errors refer to all of the inappropriate performances before the specimens are measured by analyzers, such as improper sample collection, transport delays, illegible handwriting on requisition, and so on. Most preanalytical errors are rooted outside of the clinical laboratory, although laboratory professionals are the main work force to detect these errors. Here are some case examples of preanalytical errors that occurred over a period of one week at a local hospital.

Case One
A patient blood sample looked normal without any hemolysis, but the following critical values were obtained and flagged:

  Initial test Repeated test
Ca2+ 0.6mmol/L 0.7mmol/L
K+ 15.5mmol/L 15.5mmol/L
ALK 5U/L 4U/L

 

These abnormal data were not consistent with the patient’s medical history. As a result, the medical laboratory scientist communicated this to this patient’s nurse. The medical laboratory scientist learned this patient serum sample was contaminated by EDTA-K2 because the tested sample was a combination of his blood from a purple top tube (with EDTA-K2 as coagulant) and a red top tube.

EDTA is widely known as a chelator to electrolytes, including Mg2+, Zn2+, and Ca2+. The presence of EDTA in the serum not only falsely decreases the electrolytes levels, but also inhibits the ALK test, which requires Mg2+ and Zn2+ as cofactors in the test. In addition, the K+ in the EDTA-K2 falsely elevated the potassium level, explaining the lack of observed hemolysis.

Case Two
A male patient was admitted into the hospital due to head trauma. His coagulation test showed the following test results: PT>120sec, APTT>180sec, TT>120sec, but his fibrinogen, D-dimer, and fibrin degradation product (FDP) are normal.

It is unusual for a patient to have normal levels of fibrinogen, D-dimer, and FDP with enormously prolonged PT, APTT, and TT. In order to interpret these unreasonable data, the medical laboratory scientist questioned the patient’s nurse about their collection procedure. It was identified that his nurse collected the blood using a purple top tube and then pipetted the sample into a light blue top tube for coagulation testing. It is widely known that Ca2+ is an important factor in blood coagulation, but the anticoagulant EDTA in the purple top tube could chelate the majority of the calcium ions and falsely reduced the availability of Ca2+ in the specimen, which resulted in the prolong PT, APTT, and TT but normal FIB and D-dimers.

Case Three
A patient’s chemistry measurements are listed as follows:

  Monday Tuesday
Na2+ 118mmol/L 138.5mmol/L
K+ 16.8mmol/L 4.12mmol/L
Cl– 105mmol/L 104.3mmol/L
Glu 45.05 mg/dL 93.69 mg/dL

 

The laboratory technician detected the dramatic changes in the measurements of two consecutive days and consulted with the patient’s nurse. The blood sample tested on Monday remained uncentrifuged and stored in the refrigerator over the weekend. During this storage period, the Na-K-ATP pump on the red blood cells were arrested, which caused K+ to be secreted out of the cells and Na+ to be moved into the cells. The red blood cells metabolized the glucose in the blood and decreased the glucose levels.

Case Four
The morning laboratory tests of a patient indicated as follows:

WBC 1.9*10^9
HGB 4.4 g/dl
Glu 225.230 mg/dL

 

After notifying his nurse of these critical lab values, the laboratory scientist was told the patient’s clinical presentation didn’t match these test results. The patient’s sample was collected while the patient was having intravenous therapy. The IV fluid mixed with the blood sample and diluted the components in the blood sample and caused the aberrant test results. A recollected blood sample in the afternoon produced normal test results.

Case Five
A physician ordered several tests on a patient’s stool samples. The results are as follows:

  Monday Thursday Thursday (repeated) Thursday (new sample)
Color Yellow, waterish Yellow, soft Yellow, soft Yellow, soft
WBC + — — —
RBC + — — —
Rotavirus + + + —

 

The laboratory technician discussed the controversial results with the patient’s nurse on Thursday. It turned out the sample submitted on Thursday was dropped on the floor, where some rotavirus contaminated the stool and impaired the sterility of the sample. A new sample was requested, and the test results are normal as shown in the above table.

More Potential Errors
It has become a routine task for medical laboratory professionals to identify preanalytical errors and to take corrective measures. However, some preanalytical errors are not detectable at the laboratory end, which might cause significant impacts on test results. For example, the K+ level will be elevated by 2.5 percent if the tourniquet remains in place for more than 60 seconds at a time during phlebotomy.3 Application of the tourniquet for 60-120 seconds can also cause a 5 percent increase in the total cholesterol level.4 Moreover, the declines of total bilirubin and glucose from unprocessed blood samples averaged about 2.3 percent/hour5 and 5-7 percent/hour6, respectively; therefore, if the blood sample isn’t delivered to the laboratories within four hours, the false measurements of glucose and bilirubin can significantly impact physician’s decisions on the diagnosis and treatment of patients.

Preanalytical errors significantly increase the workload of the clinical laboratory. However, most of these errors are beyond the control of laboratory administration. More critically, the credibility of clinical laboratories is at stake due to the burden of the inconsistencies or incorrect reporting that can occur from these errors. Therefore, medical laboratory professionals have taken the responsibility to advocate for the development of quality control procedures at the preanalytical phase.

Currently, new specimen collection and processing protocols are developed and investigated in nurse practices since nurses are frequently responsible for specimen collection.7,8 Some medical laboratory professionals have initiated the standardization of the management of unsuitable specimens and reporting policies to deal with preanalytical errors.9,10 The quality control of the preanalytical phase remains an issue in many clinical laboratories; medical laboratory professionals are continuously contributing to this topic and providing valid evidence for future guidelines and recommendations.

References

  1. Rachna, A., Quality-Improvement Measures as Effective Ways of Preventing Laboratory Errors. Lab Medicine, 2014. 45(2): p. 9.
  2. Plebani, M., et al., Performance criteria and quality indicators for the pre-analytical phase. Clin Chem Lab Med, 2015. 53(6): p. 943-8.
  3. Asirvatham, J.R., V. Moses, and L. Bjornson, Errors in potassium measurement: a laboratory perspective for the clinician. N Am J Med Sci, 2013. 5(4): p. 255-9.
  4. Narayanan, S., Pre and post analytical errors in lipid determination. Indian Journal of Clinical Biochemistry, 1996. 11: p. 5.
  5. Rehak, N.N., S.A. Cecco, and G.L. Hortin, Photolysis of bilirubin in serum specimens exposed to room lighting. Clin Chim Acta, 2008. 387(1-2): p. 181-3.
  6. Turchiano, M., et al., Impact of blood sample collection and processing methods on glucose levels in community outreach studies. J Environ Public Health, 2013. 2013: p. 256151.
  7. Ning, H.C., et al., Reduction in Hospital-Wide Clinical Laboratory Specimen Identification Errors following Process Interventions: A 10-Year Retrospective Observational Study. PLoS One, 2016. 11(8): p. e0160821.
  8. Simundic, A.M., et al., Joint EFLM-COLABIOCLI recommendation for venous blood sampling. Ann BiolClin (Paris), 2019. 77(2): p. 131-154.
  9. Lima-Oliveira, G., et al., Pre-analytical phase management: a review of the procedures from patient preparation to laboratory analysis. Scand J Clin Lab Invest, 2017. 77(3): p. 153-163.
  10. Cadamuro, J., et al., European survey on preanalytical sample handling – Part 2: Practices of European laboratories on monitoring and processing haemolytic, icteric and lipemic samples. On behalf of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase (WG-PRE). Biochem Med (Zagreb), 2019. 29(2): p. 020705.

Jie Gao is assistant professor in the Clinical Laboratory Sciences Program/Department of Clinical and Diagnostic Sciences at the University of Alabama at Birmingham.