This case presentation describes a 64-year-old female patient who visited the laboratory for requested tests and encountered discrepant results between two laboratories for her intact parathyroid hormone (iPTH) level. The receptionist failed to record the patient's drug history, including her use of biotin supplements. After initial testing found low iPTH, total calcium, and alkaline phosphatase levels consistent with adynamic bone disease, a second laboratory found a significantly higher iPTH level. The laboratory investigated potential pre-analytical, analytical, and post-analytical errors and determined biotin interference affected the iPTH assay, providing a falsely low result. The case highlights the importance of thorough history taking including medication

1. Rania Mohamed El-Sharkawy
rania.elsharkawy@alex-mri.edu.eg
Lecturer of clinical chemistry, MRI-Alexandria University ,CPHQ,LSSGB
Health governance –MRI-Alex university unit coordinator
IHI Egypt & NAHQ member

2. Case presentation

3. How can we achieve good laboratory
practice?
1.
A 64 year-old female went to the laboratory to perform the
investigations requested from a referring doctor.
2.
She went in to the registration unit
3.
The receptionist asked the patient to fill the registration form ,
the patient was illiterate so the receptionist tried to help the
patient and she asked for the following data:

4. History taking
(1) Full name of the patient
(2) Age
(3) Telephone and Address of the patient
(4) Referring doctor name and address (contact)
(5) History of chronic illness
(6) History of surgeries
(7) Requested analytical tests ( fasting hours)

5. How can we achieve good laboratory practice?
What information did she
forget to take from the
patient?

6. How can we achieve good laboratory practice?
The patient is suffering from chronic renal failure
(dialysis) and the doctor requested the following
investigations:
1. Total calcium level
2. Alkaline phosphatase
3. Intact parathyroid hormone

7. How can we achieve good laboratory practice?
Sampling unit
(1)The phlebotomist took the sample
following accurate sampling procedure
(2)The sample was transported to the
central laboratory for processing

8. The patient returned back to the laboratory
complaining from discrepancy between both laboratory
results?
How Can the lab
ASSURES THE PATIENT SATISFACTION
together with
Identifying the source of error

9. Laboratory results
Total calcium level
10.3 mg/dL (reference interval 8.4-10.5 mg/dL) Total calcium level
10.3 mg/dL (reference interval 8.4-10.5 mg/dL)
Alkaline phosphatase
160 U/L (reference range 30-120 U/l . Mild increase in activity)
Intact Parathyroid hormone level were low
40pg/ml (16-87 pg/ml)

10. Immediately after withdrawing the sample the
patient went to another laboratory to repeat
the investigations
All the results were comparable except for the
PTH it was significantly higher
500 pg/ml

11. How can we achieve good laboratory
practice?
What might occur in this process that may
affect the next process?

12. This is a problem that may face any
laboratory
Why is the best approach to this problem?
Where is the problem?
How can the laboratory be confident about his results?

13. What is the best practice to this problem?
Ensure your customer satisfaction
by settling a firm, well
communicated patient complaint
handling policy?

14. What is the best practice to this problem?
Contact his doctor to gather full clinical
information about the patient`s
condition
Here comes the importance of the doctor
name and contact

15. What is the clinical interpretation of this case?
•
PTH functions to maintain serum calcium concentrations within a tight
physiologic range
• Patients with chronic renal failure develop secondary hyperparathyroidism owing
to decreased renal production of 1,25-dihydroxyvitamin D, decreased Ca and
hyperphosphatemia.
•These derangements in mineral metabolism stimulate PTH production to raise
serum calcium and promote phosphorus excretion.
• Increased serum PTH leads to excessive bone resorption through stimulation of
osteoblasts and osteoclasts

16. What is the clinical interpretation of this case?
•The combination of secondary hyperparathyroidism and mineralization defects
(osteomalacia) represents the most common form of renal osteodystrophy
(ROD).
•Subtype of ROD known as adynamic bone disease can be observed in the
setting of prolonged peritoneal or hemodialysis, over suppression of PTH with
calcitriol or calcium-based phosphate binders, or the use of bisphosphonates for
osteoporosis treatment
• Common biochemical hallmarks of ABD include hypercalcemia, low or
inappropriately normal PTH concentrations, and reduced markers of bone
turnover (e.g., alkaline phosphatase)

17. The laboratory findings
Are consistent with
Renal osteodestrophy as regards:
 Borderline Calcium level
 Increased alkaline phosphatase
Decreased iPTH
What is not with ROD?

18. The laboratory findings which
Are consistent with
Adynamic bone disease as regards:
 Borderline Calcium level (towards hypercalcemia)
 Decreased iPTH
Increased alkaline phosphatase
( it should be low due to decreased bone turnover)
What is not with ABD

19. This is a problem that may face any
laboratory
Why is the best approach to this problem?
Where is the problem?
How can the laboratory be confident about his

21. Where is the problem?
The problem has to be investigated systematically
(1) Pre-analytical
(2) Analytical
(3) Postanalytical

22. Incidence of pre-analytical variables 46-68.7%
97
Exclude the following:
•Patient related variables (drug history
2% of errors)
•Specimen related variables
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23. How can we achieve good laboratory
practice?
What information did she forget to take
from the patients?

24. How can we achieve good laboratory practice?
History taking
(1) Full name of the patient
(2) Age
(3) Telephone and Address of the patient
(4) Referring doctor name and address (contact)
(5) History of chronic illness
(6) History of surgeries
(7) Requested analytical tests (preparation)

25. The drug history………..
•
The patient is receiving 10 mg /day biotin
•
Biotin has been reported to improve symptoms of
encephalopathy and peripheral neuropathy in patients with
RF and undergoing hemodialysis
•
Also she is taking Ca based phosphate binders
•
Vitamin D

26. How can we achieve good laboratory practice?
Sampling & transportation processes
(4) sample can be stored at 2-8C for 8h
after collection or longer stored up to 2
month in – 20C.

27. What are the possible causes of
error in the sampling and
transportation processes?

28. Incidence of pre-analytical variables 46-68.7%
97
Exclude the following:f
•Patient related variables (drug history
2% of errors)
•Specimen related variables
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29. How can we achieve good laboratory practice?
Sampling & transportation processes
(1) Morning sample was taken(nocturnal rise)
(2) EDTA (filled to the desired mark on the tube as excess
EDTA will interfere with the assay causing false decrease )or
serum sample could be taken .
(3) Rapid collection and separation of the sample using
refrigerated centrifuge to keep the sample at 2-8C.

31. How can we achieve good laboratory practice?
Analytical process
1.
2.
3.
Revise the reference interval & validation of the method
Apply acceptance , rejection criteria
Reconstitute the control or adjustor vial with accurate amount of distilled
water using calibrated pipette and should be put in ice in between swirling.
4.
Introduce the control, judge on the control
5.
Introduce sample

32. How can we achieve good laboratory
practice?
Analytical process
(5) Verify the result
(6) Release the report

33. The principle of the method in our laboratory
A biotinylated anti-PTH monoclonal antibody and a ruthenium-labeled antiPTH monoclonal antibody form a sandwich complex with PTH
After which streptavidin-coated microparticles are added to magnetically
separate out the sandwich complex via biotin and streptavidin interaction
Specimens with high concentrations of biotin may prevent the
binding of the sandwich complex to the streptavidin-coated micro
particles, thus giving falsely low signals

34. The principle of the method in our
laboratory
Biotin is recognized as a potential interferent in PTH and
other assays that uses the same method, and it is
recommended in the product insert that samples from
patients receiving high biotin doses of >5 mg/day be
collected at least 8 h after biotin administration

35. HOW CAN THE LAB verify the error ?
•Using another method (importance of backup plans)
• To confirm the interfering role of biotin , iPTH concentration were measured
in two labs after the patient stopped taking the drug for 2 weeks (both results
were the same)
•Recovery experiment using both normal and increased i PTH levels
.

36. Figure 1. Effect of biotin on serum intact PTH concentrations determined using our method.
Percent recovery was calculated as the ratio of PTH concentration after the addition of biotin at
various concentrations (sigma –Aldrich) (5, 10, 20, 40, 80, 160 µg/L) to the samples.( solid diamond
indicates normal level& solid square indicates increased level)

37. This is a problem that may face any laboratory
Why is the best approach to this problem?
Where is the problem?
How can the laboratory be confident about his results?

38. Incidence of analytical errors 7-13%
Confirm the following
 Validation of method
IQC results
EQAS results
Uncertainty of measurements
Total allowable error
•Revise your reference interval or establish…
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39. Incidence of Post-analytical variables
18-47%
Confirm the following:
 Error in recording
Errors in reporting
Errors in interpretations???(role of lab doctors)
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40. Conclusion……….
pre-analytical errors:
Improper identification of the patient
Drug history
 analytical errors
Interference and no backup plans
Postanalytical :
No analytical validation of the test result and halting the report should be done

41. Data collection period
I year
1 year
1 year
No. of tests
997 000
600 000
40 490
No. of patients
249 000
160 714
10 000
120
180
189
0.05% of patients
0.11% of patients
0.47% of test results
Preanalytical phase
31.6%
55.6%
68.2%
Analytical phase
31.6%
13.3% overall
(4.4% if referral laboratory
13.3%
Postanalytical phase
30.8%
30%
18.5%
No. of errors
Frequency
Mulitiple phases
6%

42. Finally……….
Define the processes
 The lab should standardize its operating procedures according to national or
international standards..
Put a control measures to each process.
 Standardize the laboratory error detection program.
Using (process analysis, audit , questionnaires , and collection of complaints)
 Accurate analysis of the errors

43. Finally……….
Define ways to decrease laboratory errors and to possibly avoid
completely those with a real or potentially significant negative
effect on a patient’s health.
And here starts the improvement that should
never ends………………