QUALITY MANAGEMENT IN CLINICAL BIOCHEMISTRY

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QUALITY MANAGEMENT IN CLINICAL BIOCHEMISTRY  

• Dr. Charles D. Stephen
• Dept. of Clinical Biochemistry
• CMC, Vellore

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• WHAT IS QUALITY?
•  
• Conformance to the requirements of user or
  customers
•  
• Directly.
•  
• Satisfaction of the needs and expectations of
  users or customers

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FIVE Q Framework
Quality Planning
Goals Objectives Quality Requirements
Quality Lab Processes
Quality Improvement
Quality Control
Quality Assessment
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• PDCA CYCLE
•   PLAN
• DO
• CHECK
• ACT
•   QP - PROVIDES THE PLANNING STEP
•   QLP - ESTABLISHES STANDARD PROCESS
  FOR DOING THINGS
•   QC AND - PROVIDES MEASURES FOR
• QA CHECKING , HOW WELL THINGS
  
• ARE DONE
•   QI - PROVIDES MECHANISAM FOR ACTING
  ON THESE MEASURES

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QUALITY ASSURANCE REQUIRES

• 1. CAUSES OF PROBLEMS BE IDENTIFIED AND
  ELIMINATED
•  
• 2. DETECTION OF THE PROBLEMS
  EARLY ENOUGH TO PREVENT THEIR
  CONSEQUENCES

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ELEMENTS OF QUALITY ASSURANCE

• 1. COMMITMENT
• Dedication to quality service must be central. A
  true commitment is required by Lab Directors,
• Managers and Supervisors if the efforts of the
  lab personnel are to be successful.

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2.FACILITIES AND RESOURCES

• Lab must have the administrative support
  necessary to provide the quality of services that
  is desired.
• This means having ,
• adequate space,
• equipment,
• materials,
• supplies,
• staffing,
• supervision and
• budgetary Resources.
• These resources provide the basis upon which
  quality services can be developed and maintained.

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3. TECHNICAL COMPETENCE

• High quality personnel are essential for high
  quality services. The educational background and
  experience are important. In service training can
  develop and maintain skills.

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4. TECHNICAL PROCEDURES

• Good technical procedures are necessary
• Control of preanalytical conditions or variables
  such as
• Test requests
• Patient preparation
• Patient identification
• Specimen acquisition
• Specimen transport
• Specimen processing
• Specimen distribution
• Preparation of work lists and logs
• Maintenance of records

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• Control of analytical variables, which includes
•   Analytical methodology
• Standardization and calibration procedures
• Documentation of analytical protocols and
  procedures
• Monitoring of critical equipment and materials
•   Monitoring of analytical quantity by the use
  of statistical methods and control charts. 

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• CONTROL OF PREANALYTICAL VARIABLES
• The responsibility for accurate and timely test
  reports generally lies with the laboratory but
  many problems can arise prior to and after the
  analysis of the submitted specimens.
•  
• So it is essential to perform a system analysis
  of the laboratory and to identify the type of
  preanalytical variables.

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• LABORATORY TESTING PROCESSES AND THEIR POTENTIAL
  ERRORS
•   PRE ANALYTICAL ERRORS
•  
• PROCESS POTENTIAL ERRORS
•  Test ordering inappropriate test
• Handwriting not legible
• Wrong patients ID
• Special requirements not specified
•  Specimen acquisition
• Incorrect tube or container
• Incorrect patient ID
• Inadequate volume
• Invalid specimen
• (hemolysed or diluted) Collected at wrong
  time
• Improper transport conditions

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• ANALYTICAL ERRORS
•  Analytical Instrument not calibrated
  Measurement correctly
• Specimens mix up
• Incorrect volume of specimen
• Interfering substances present
• Instrument precision problem
• Test reporting Wrong patient ID
• Report not legible
• Report delayed
• Transcription error

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• POST ANALYTICAL ERRORS
•  
• Test interpretation Interfering substance not
  recognized
• Specificity of the test not understood
• Precision limitation not recognized
• Analytical sensitivity not appropriate
• Previous values not available for
  comparison

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• HOW TO CONTROL THESE ERRORS?
•  PRE ANALYTICAL VARIABLES
•   It is very difficult to establish effective
  methods for monitoring and controlling
  preanalytical variables because may of the
  variables are outside the laboratory areas.
•   Requires the coordinated effort of many
  individuals and hospital departments
•  Patient Identification
•   The highest frequency of errors occurs with the
  use of handwritten labels and request forms. The
  use of bar code technology has significantly
  reduced ID problems.
• Turnaround time
• Delayed and lost test requisitions, specimens
  and reports can be major problems for labs.
  Recording of the actual times of specimen
  collection, receipt in the lab and reporting of
  results with use of computers will solve these
  problems.

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• Transcription error
•   A substantial risk of transcription error
  exists from manual entry of data even with the
  double checking of results, computerization will
  reduce this type of transcription error.
•  Patient preparation
•  Lab tests are affected by many factors, such
  as,
• recent intake of food, alcohol, or drugs
• smoking
• exercise
• stress
• sleep
• posture during specimen collection
• The lab must define the instructions and
  procedures compliance with these instructions can
  be monitored directly efforts should be made to
  correct non compliance

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• Specimen Collection
•   Prolonged tourniquet application causes local
  anoxia to cells and excessive venous
  backpressure, venous stasis and
  hemoconcentration.
•   Blood collection from an arm into which an
  intravenous infusion is running can be diluted or
  contaminated.
•  Hemolysis during blood collection
• Improper containers with incorrect preservatives
  
•   To monitor and control these problems,
  specially trained lab team assigned to specimen
  collection
• The identification of the person collection a
  specimen should be maintained
•  Clinicians should be encouraged to report
  clinically inconsistent results.
• Pride of workmanship should be encouraged and
  quality performance should be rewarded.
•  
• Specimen transport
• The stability of specimens during transport from
  the patient to the lab is seldom monitored

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• CONTROL OF ANALYTICAL VARIABLES
• There are many analytical variables that must be
  carefully controlled
• Water quality
• Calibration of analytical balances
• Calibration of volumetric glassware and pipets
• Stability of electrical power
• Stability of temperature of heating baths,
  refrigerators, freezers and centrifuges

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• The procedure Manual should contain the following
• Procedure name
• Clinical significance
• Principle of method
• Specimen of choice
• Reagents and equipments
• Procedure
• Reference values
• Comments
• References

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• CONTROL OF THE ANALYTICAL QUALITY USING
  STABLE CONTROL MATERIALS
• The performance of analytical methods can be
  monitored by analyzing specimens whose
  concentrations are known and then by comparing
  the observed values with known values.
• The known values are usually represented by an
  interval of acceptable values, or upper and lower
  limits for control (control limits)
• When the observed values fall within the control
  limits analysis is working properly
• When the observed value fall outside the control
  limits the analyst should be alerted to the
  possibility of problems in the analysis.

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• GENERAL PRINCIPLES OF CONTROL CHARTS
•  
• Control charts are simple graphical displays in
  which the observed values are plotted versus the
  time when the observations are made.
•  
• The control limits are calculated from the mean
  (x) and standard deviations (s)

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DEFINITIONS

• Accuracy
• Precision

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SD

• Standard deviation - extent of random variation
• SD ?d2
• n-1
• d difference of individual result from mean
• n number of observations

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CV

• Co-efficient of variation
• relative magnitude of variability while
• comparing two procedures
• CV (SD x 100)/mean

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ACCURACY AND PRECISION
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Good Accuracy Good Precision
Good Precision Only
Neither Good precision Nor Accuracy
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Levey-Jennings Control Chart
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• DETERMINATION OF GLUCOSE IN BODY FLUIDS
•  Specimen collection and storage
•   Whole blood glucose concentration is app. 12 to
  15 lower than the plasma or serum glucose.
• (with normal hematocrit)
•   water content of plasma (93) is app. 12
  higher than the whole blood .
•   Glycolysis decreases serum glucose by 5 to 7
  in 1 hour (5 10 mg/dl) in uncentrifuged
  coagulated blood at RT.
•   Glycoslysis decreases serum glucose in
  leukocytosis or bacterial contamination.
• Serum separated from cells in sterile
  conditions, glucose concentration is stable for 8
  hrs at 25C and up to 72 hrs at 4 C.
•   Glycolysis can be prevented and glucose
  stabilized for as long as 3 days at RT by adding
  sodium fluoride (NaF)
• Anti coagulant K EDTA and NaF (22 mg ) per
  ml of blood is added in the blood collection tube
  for glucose.

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• METHODS
•  Hexokinase method (highly accurate)
• Hexokinase
• Glucose ATP __________ ____G - 6 P ADP
•  
• G6PD
• G-6-P NAD _____ 6 Phosphogluconate NADH
•  
•  
• Interference by hemolysis (0.5 g Hb) unsuitable
• Lipemic ( Tggt 500 mg/dl) positive error.
• Icterus (gt TB 5 mg/dl) Negative error

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• GOD POD METHOD
• GOD
• GLUCOSE O2 Gluconic acid H2O2
•  
• POD
• H2O2 Phenol quinoneimine dye
• 4 amino antipyrine (red in color) H2O
•  
• First step is specific for glucose
•   Second step is much less specific UA, AA,
  BILIRUBIN, HEMOGLOBIN, TETRACYLINE
• AND GLUTOTHIONE INHIBIT the reaction NEGATIVE
  ERROR
•   Method is suitable for CSF but NOT for URINE

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• REFERENCE INTERVALS (FASTING)
•  ADULTS 74 106 mg/dl
•  CHILDREN 60 100 mg/dL
•  PREMATURE NEONATES 20 - 60 mg/dl
• TERM NEONATES 30 - 60 mg/dl
•  NO SEX DIFFERENCE
•   FASTING VALUE INCREASES WITH AGE APP 2
  mg/dl per decade
•   PP VALUE INCREASES WITH 4 mg/dl per decade

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• SEMI QUANTITATIVE MEASUREMENT OF URINE GLUCOSE
• OLD METHODS USE BENEDICTS REAGENT
• BASED ON REDUCING PROPERTY OF GLUCOSE
• ALL REDUCING SUBSTANCES IN URINE ALSO INTERFERE
• GIVING FALSE POSITIVE ERROR
• ANALYTICAL SENSITIVITY 250 mg/dl
• NEW METHODS CONVENIENT - PAPER STRIPS
  COMMERCIALLY AVAILABLE

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• USE GLUCOSE SPECIFIC ENZYME REAGENTS
• ANALYTICAL SENSITIVITY 100 mg/dl
• FALSE POSITIVE RESULTS BY CONTAMINATION WITH
  HYPOCHLORITE (BLEACH)
• FALSE NEGATIVE RESULTS WITH LARGE QUANTITY OF
  KETONES, ASCORBIC ACID
• AND SALYCYLATES.
• Estimating Blood glucose concentration by
  monitoring urine glucose is UNDESIRABLE

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• ESTIMATION OF SERUM CREATININE
•  JAFFE MATHOD
•  PRINCIPLE
• Creatinine Picric acid NaOH Creatinine
  picric acid complex ( yellow orange in color)
• Specimen Collection and Preparation
• Serum, Heparinized or EDTA plasma can be used
• Stability 7 days at 2 8 C
• Freeze for long term storage
• (Urine 4 days at 2 8 C and Freeze for long
  term storage)

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• LIMITATIONS AND INTERFERENCE 
• ICTERUS
• No significant interference up to 10 mg/dl of
  T.Bilirubin
• Analytical Correction should be made for
  specimen with TB gt 10 mg/dl ( NEGATIVE ERROR)
•  HEMOLYSIS
• No significant interference up to 750 mg/dl of
  Hb
•   LIPEMIA
•   No significant interference up to Tg 2000
  mg/dl

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• KETONE BODIES
• Positive Error ( up to 3 mg/dl) with increasing
  concentration of Acetoacetate ( 8 mmol/L)
•   MANY SUBSTANCES INCLUDING PROTEIN, GLUCOSE,
  ASCORBIC ACID, ACETONE, ACETOACETATE, PYRUVATE,
  AND GUANIDINE INTERFERE WITH CREATININE AND
  PRODUCE FALSE POSITIVE ERROR.
•   HOWEVER, THE MODIFIED KITETIC ASSAY OF JAFFE
  REACTION PROVIDES IMPROVED SPECIFICITY
•   Expected values
•  Men 0.7 - 1.3
  mg/dl
• Women 0.6 - 1.1

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• ESTIMATION OF SERUM CHOLESTEROL
• ENZYMATIC COLORIMETRIC METHOD USES CHOLESTEROL
  ESTERASE, CHOLESTEROL OXIDASE AND PEROXIDASE
  ENZYME WITH CHROMOZEN SIMILAR TO THAT USED IN
  GLUCOSE ESTIMATION.
• SPECIMEN COLLECTION AND STORAGE
• Serum, Heparin zed or EDTA plasma can be used
• Stability 5 7 days at 4C
• 3 months at 20C
• Fasting and non-fasting samples can be used.

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• LIMITATIONS AND INTERFERENCE
•  
• Not affected by Hemolysis, uric acid, or
  bilirubin in concentrations below 5 mg/dl.
•  
• REFERENCE RANGE
•  
• Desirable - lt 200 mg/dl
• Borderline - 200 - 239 mg/dl
• High - gt 240 mg/dl

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• MICROALBUMINURIA ASSAY
• IMMUNO TURBIDIMETRIC ASSAY
• USES MONOCLONAL ANTISERUM REAGENT
• HIGHLY SPECIFIC AND SENSITIVE
• SAMPLE PREPARATION
• Spot urine sample
• For screening of microalbuminuria a spot sample
  of urine can be used.
• First morning voided urine is preferable
• The urine can be stored at 4 C for 14 days
• Should NOT be frozen

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• Expected Values
•  
• Spot urine lt 20 mg/L
•  
• Microalbuminuria is defined as an albumin
  concentration of 20 200 mg/L in a spot urine
  samples.
•  
• Microalbuminuria is confirmed if at least two
  out of three samples are positive over a period
  of three to six months.