Lab & Diagnostic test

Dr. Shymaa Shehata

Harvard CSRT Batch A
Head of the Scientific Research Department at MIH
Pharm D, BCPS, TOT & Clinical Pharmacotherapy
Specialist at MIH
 Outline
• Introduction of Lab interpretation in the context of clinical picture
• Blood tests
1. CBC interpretation
2. Coagulation profile / Hemostasis Tests (INR, aPTT, Platelets, D-dimer)
3. Blood glucose tests interpretation
4. Lipid profile interpretation
5. Liver Function Tests (LFTs) Interpretation
6. Kidney function test interpretation

• Urine analysis
• Microbiology Testing
Laboratory Tests…..Definition
• Clinical chemistry uses chemical processes to measure levels of
chemical components in body fluids and tissues.

Laboratory Interpretation…..Definition
Interpretation of laboratory results means understanding the meaning
of numbers that we obtain when tests are done.

This is important if the correct diagnosis is to be made, or if the

patients treatment is to be changed.
1- GENERAL PRINCIPLES
• Generally, laboratory tests should be ordered only:

A-If the results of the test will affect decisions about the care of the
patient or at least monitoring and follow-up.

B- The serum, urine, and other bodily fluids can be analyzed routinely;
however, the economic cost of obtaining these data must always be
balanced by benefits to patient outcomes.
2- Reference ranges
Biochemical test results are usually compared to a reference range
considered to represent the normal healthy state.

Most Reference Ranges are made by including 95 % of the values found

in healthy volunteers. Although, 5 % of the population will have a result
out the reference range.
What does Normal range mean?

Clinical laboratory test results

that appear within a
predetermined range of values
are referred to as “normal,”

and those outside this range are

typically referred to as
“abnormal.”

But….
There is often a degree of overlap between the disease state and normal value.

A patient with an ABNORMAL result who is found NOT to have the disease is a
false positive.
A patient who has the disease but has NORMAL result is a false negative.
Factors can interfere with the accuracy of laboratory tests

A- Patient related factors

(e.g. age, gender, medication, diet, time since last meal, pregnancy,
menstrual cycle) can affect the range of normal values for a given test

1- Age (e.g. new born baby has high HCT)

2- Gender (e.g. HGB/ HCT in male and female)
B- Laboratory based issues can also influence the accuracy of laboratory
values.
• For example, a specimen can be spoiled
• because of improper handling or processing (e g hyperkalemia due to hydrolysis of a
blood specimen)
• because it was taken at a wrong time (e g fasting blood glucose level taken shortly
after a meal)
• because collection was incomplete (e g 24-hour urine collection that does not span a
full 24-hour period)

Clinical laboratories can analyze sample specimens by different laboratory methods;

therefore, each laboratory has its own set of normal values.

Consequently, clinicians should rely on normal values listed by their own clinical
laboratory facility when interpreting laboratory tests.
Peak and trough level
•Peak levels are done to ensure a patient is
getting a therapeutic level of medication but
not becoming toxic and causing kidney
damage.

•Peaks commonly are done 30 min to 1 hour

after completion of every 3rd dose. Then
pharmacy adjusts dosage as needed.
 3- Laboratory Error Examples
A variety of factors can interfere with the accuracy of laboratory tests:

1- Laboratory-based issues can also influence the accuracy of laboratory

values. For example, a specimen can be spoiled (e.g. ABG)

2- Errors also can arise due to faulty poor quality reagents (e.g., improperly
prepared, outdated)

3-Due to technical errors (e.g., human error in reading result, computer-

typing error)
4-Due to dietary effects (e.g., rare or red meat ingestion can cause a false-
positive Fecal Occult Blood test)

5-Because medications can interfere either with the testing procedure or by

their pharmacologic effects (e.g., thiazides can increase the serum uric acid
concentration, β-agonists can reduce serum potassium concentrations).

As a result, laboratory findings must always be

interpreted carefully, and the validity of a test result
questioned when it does not seem to correlate with a
patient’s clinical status.
4- Units of the Lab value
• D-Dimer normal range is
• ≤ 500 ng/mL
• or
• ≤0.5 mg/L
 5- Diagnostic vs prognostic value
• To select a proper diagnostic test,
• It is recommended that the most specific test be used to confirm
(rule in) a diagnosis,
• The most sensitive test be used to establish that a disease is unlikely
(rule out).
Example of prognostic test
• Acute phase reactants are two types:

• Positive acute phase reactants: substances that increases in serum

level in case of inflammation examples C-reactive protein, ferritin

• Negative acute phase reactants: substances that decrease in serum

level in case of inflammation examples albumin, transferrin
C-Reactive Protein (CRP) More specific
than ESR

• is an Positive acute phase reactant, a protein made by the liver and

released into the blood within a few hours after tissue injury, the
start of an infection, or other cause of inflammation.

So in case of liver
failure or starvation Faster than
it is invalid indicator ESR
C-Reactive Protein (CRP)

• Normal range :
• CRP < 6
• ESR in 1st hr. female <20
• Male <15
• Use of CRP in the evaluation of febrile illness .
• High CRP values rule out viral infection as a sole etiology of infection
• Elevated CRP values (> 40 mg/l) are typical for bacterial infections,
but may also be recorded in some viral infections.
Because viral infections do not
typically increase in CRP serum
concentrations,

the use of CRP as a diagnostic

tool to differentiate viral versus
bacterial meningitis might be
clinically helpful.
6- Measured value vs estimated value
• Serum creatinine Creatinine clearance
• A blood specimen was taken from a
65-year-old woman to check her
serum potassium concentration as
she had been on thiazide diuretics
for some time. The GP left the
specimen in his car and dropped it
off at the laboratory on the way to
the surgery the next morning.

• Immediately on analyzing the sample

the biochemist was on the phone to
the GP. Why?
• "A serum potassium
concentration of 45 mmol/l was
recorded in the notes of a 35-
year-old man being prepared for
appendicectomy. The set of
electrolyte results had been
phoned from the laboratory.

• The consultant surgeon was not

annoyed , although he did check
the results on the ward himself.
Why?"
1- CBC interpretation
CBC Pearls
• Clinicians have a short-hand way to report CBC values:
WBCs
• WBCs are involved in the immune response.
• The normal range: 4.5 – 11x10^9 /L
• Two types of WBC:
• 1) Granulocytes consist of:
Neutrophils: 50 - 70%
Eosinophils: 1 - 5%
Basophils: up to 1% Request
• 2) Agranulocytes consist of: CBC with differential
Lymphocytes: 20 - 40%
Monocytes: 1 - 6% Or blood film
 Leukopenia
(WBCs < 4.5x10^9 /L) may result from:

1- Decreased WBC
production from BM.

2- Irradiation.

3- Exposure to
chemical or
drugs.
Leukocytosis (WBCs > 11x10^9 /L)
1- Watch the trend !!
• If the value is 13

20 13 5 13

• 2- Differentials: Bands ,segs , L, M, E

• Neutrophils + Pyrogenic infection characterized by severe
local inflammation typically with pus formation
3- Possible causes Neutrophils Bacterial infections

According to the Allergy depends

upon its
parasitic infections
differentials Eosinophils
Fungal infection (esp. primary
Cocci) function

Lymphocytes
Viral infections , TB

CMV or pertussis

Post acute infection

typhoid
fever
BMS
General possible causes of Leukocytosis
1- Infection
Left shift bands >> seg(PMNs)
Fever, signs of infection and pain ( do not forget C. diff)
Chest X ray , UA, CT, LP
2- Steroids increase WBCs due to:
Demarginating 60%
Delayed migration 30%
Increase Band release 10% (with increase of other differentials)
3- Cancer/ Leukemia
Different according to type ALL,CLL,AML,CML
Need BMB
4- Catastrophic events
• E.g. MI, Cardiac Arrest, Massive PE
• With acute spike increase
Platelets
Platelet Count Normal count is 140,000 to 440,000/mm3
Life span of about 10 days

Thrombocytopenia is a Low platelet counts (< 140,000 /mm3)

Thrombocytopenia manifestation
Petechial hemorrhage.
Easy bruising.
Mucosal bleeding
e.g. epistaxis.
gum bleeding

Thrombocytosis is a high platelet counts (> 440,000/mm3)

Thrombocytosis manifestation
Non specific signs and symptoms related to blood clots and bleeding, including: Headache, Dizziness or
lightheadedness and Chest pain.
So, The values have to fit the clinical situation.
But it is not important how many RBCS
are there?
but
the importance of how much oxygen
they can carry??

Red Blood Cells (Erythrocytes)

Produced in the bone marrow
Life span of about 120 days
Primary function is gas transport
Immature version has nucleus and is called a reticulocyte
HGB & HCT and The Rule of Three

Applies to normocytic, normochromic

erythrocytes only

Assess the hydration status

3 times the RBC count should = Hgb

3 times Hgb should = Hct
Increase in MCV is known as Macrocytic anemia.
Decrease in MCV is known as Microcytic anemia.
Measure of the concentration of hemoglobin
in an average RBC
Decrease in MCHC is known as Hypochromic
anemia
Normal is known as Normochromic anemia.
High RDW ---- High variation ---
Anisocytosis (nonspecific finding)

Low RDW -------Homogenous sizes

Common causes of anemias
• Normocytic anemias
• Blood loss
• Hemolytic anemia
• Microcytic anemias (<80 fL*)
• Iron deficiency
• Macrocytic anemias (>100 fL)
• Folic acid deficiency
• Vitamin B12 deficiency
• Some COPD patients
*femtoliters
10.6 *3 = 31.8

Microcytic

Hypochromic
2- Hemostasis Tests (INR, aPTT,
Platelets, D-dimer)
Monitoring of
Warfarin
 The international normalized ratio (INR)
• Normal range 0.9-1.2 or ≤ 1.2
• But Therapeutic range 2 – 3
• or 2.5 – 3.5 in mechanical mitral prosthetic valve

• Critical value >4

• When I can take vit k ?

• IF > 10 or active bleeding take vit. K
• according to:
• MINOR bleeding oral 2.5-5 mg
• MAJOR bleeding IV 5-10 mg
 Monitor
Unfractionated
heparin therapy
3- Blood glucose tests
interpretation
 Diagnostic criteria for diagnosis

A1C = HbA1c =(Hemoglobin A1c)

FPG = Fasting Plasma Glucose
OGTT = Oral Glucose Tolerance Test
 Some tips and tricks
A1c test

The A1c test, however, should not be used for:

Diagnosis of
1. Gestational diabetes in pregnant women
2. Diabetes in children and teens
People who
1. Have had recent severe bleeding or blood transfusions
fasting hours from • Not accurate 2. Chronic kidney disease or liver disease
8 up to12
More than that will be • Take second 3. With blood disorders such as iron-deficiency anemia and
drop vitamin B12 deficiency anemia
falsely high
4. With some hemoglobin variants (e.g., sickle cell disease
or thalassemia)
 Impaired
Impaired
Fasting
Glucose
Glucose
Tolerance
4- Lipid profile interpretation
• A lipid profile is a blood test that measures the amount of cholesterol and
fats called triglycerides in the blood.

• Cholesterol and triglycerides in the blood can clog arteries, making you
more likely to develop heart disease. Thus, these tests can help predict
your risk of heart disease and allow you to make early lifestyle changes
that lower cholesterol and triglycerides.

• Elevated TG and low HDL levels are more predictive of cardiovascular risk
in women than in men

• Proof of treatment benefit is strongest for lowering elevated low-density

lipoprotein (LDL) levels.
• In the overall population, evidence is less strong for a benefit from
lowering elevated TG and increasing low high-density lipoprotein (HDL)
levels, in part because elevated TG and low HDL levels are more predictive
of cardiovascular risk in women than in men
• Some reports also include:

• Total cholesterol to HDL ratio: The amount of total cholesterol divided

by HDL. This number is useful in helping doctors predict the risk of
developing atherosclerosis (plaque build-up inside the arteries).

• Very low-density lipoprotein (VLDL): Another type of bad cholesterol

that builds up inside the arteries.
• TC, TGs, and HDL cholesterol are measured directly.

• TC and HDL cholesterol can be measured in the non-fasting state, but

most patients should have all lipids measured while fasting for
maximum accuracy and consistency.

• Testing should be postponed until after resolution of acute illness,

because TGs increase and cholesterol levels decrease in
inflammatory states.

• Lipid profiles can vary for about 30 days after an acute MI; however,
results obtained within 24 h after MI are usually reliable enough to
guide initial lipid-lowering therapy.
5- Liver Function Tests (LFTs)
Interpretation
 Case
• V.C. is a 38-year-old man suffers from somnolence, and irritability and his laboratory
tests revealed the following: albumin, 2.0 g/dL(normal, 4–6); Ca, 6.8 mg/dL
(normal, 8.8–10.2); total bilirubin, 10.8 mg/dL (normal, 0.1–1.0); serum AST, 280
units/L (normal, 0–35); and alkaline phosphatase, 240 units/L (normal, 30–120).

• Why is calcium treatment inappropriate despite V.C.’s apparent low serum

concentration of calcium?

Answer
Because calcium in the serum is partially bound to plasma proteins (mostly albumin), the serum calcium
concentration is affected by the concentration of these plasma proteins.
If the albumin concentration is low, the reported serum calcium will generally be less than the lower limit of normal.
A useful method to estimate a corrected value for serum calcium in the presence of a low serum albumin is to use
the following guideline:

the total serum calcium will decrease by 0.8 mg/dL for each decrease of 1.0 g/dL in serum albumin concentration.
The “corrected” serum calcium concentration falls within the
normal range, and V.C. should not be treated with calcium
based on the available data.

Direct measurement of ionized calcium is independent of

albumin concentration, making it unnecessary to correct
calcium concentrations in the presence of hypoalbuminemia.

Unfortunately, some clinical laboratories do not have the

capability of measuring ionized calcium
Why there
is a yellow
color?
Occur In adult
Sampling should
if total bilirubin > 2.5
protect from light
– 3 mg/dl
6- Kidney function tests
interpretation
• SERUM UREA ( normal range 20- 45 mg/dl)
• Urea is the end product of protein catabolism.

• Is not an excellent marker of renal dysfunction as it rises quite late

(only when GFR<50% and its rise is also not exclusive to kidney
dysfunction

• BLOOD UREA NITROGEN (BUN) (normal range 5-26 mg/dl )

• Sometimes the Serum urea level is expressed as blood urea nitrogen.
BUN can be easily calculated from the serum urea level
Common etiology of abnormal BUN

Increased BUN (decrease Decrease BUN (increase

renal filtration) renal filtration)

Shock Malnutrition/
Hemorrhage malabsorption
CHF Liver failure
MI Overhydration
Stress SIADH
Increase protein intake
Uric acid
• is an end product of purine metabolism. It serves no biological function, is
not metabolized, and must be excreted renally.

• Gout is usually associated with increased serum concentrations of uric acid

and deposits of monosodium urate.

• Increased serum uric acid concentrations can result from either

• A decrease in urate excretion (e.g., renal dysfunction) or
• Excessive urate production (e.g., increased purine metabolism resulting
from cytotoxic therapy of neoplastic or myeloproliferative disorders).
• SERUM CREATININE LEVEL

• Creatine is a small tripeptide found in the muscles. It is released from the

muscles during regular wear and tear and is converted to creatinine.

• It is to be remembered that unlike urea, creatinine is not a toxic waste. It

is simply used as a marker of renal function.

• Normal serum creatinine level is 0.6 to 1.2 mg/dl. Serum creatinine is a

better indicator of renal function and more specifically glomerular
function than urea.
• SERUM CREATININE LEVEL

• For a particular individual the creatinine level is dependent on the muscle

mass and muscle wear and tear.

• There may be significant difference in creatinine level of

individuals with vastly differing muscle mass. For example a body
builder or athlete will have higher creatinine levels than a sedentary desk
worker.

• Similarly creatinine level will also increase in case of any muscle

trauma or excessive wear and tear as seems in athletes and
people involved in hard physical labor.
 Creatinine Clearance
A doubling of the S.Cr. level roughly corresponds to a 50% reduction in the GFR. This general rule of
thumb only holds true for steady-state creatinine levels

• (Cockcroft-Gault Equation) • (Jelliffe Multi-Step Equation)

 Case
• M.C. is a 65-year-old woman(weight =60 kg). she was given digoxin 0.125
mg/day, and a S.Cr. was ordered to further assess her renal function. The
clinical laboratory determined her S.Cr. was 1.2 mg/dL.

• Although this laboratory test result is within normal limits, it not clearly
indicate normal renal function for M.C.
Because

As patients become older, muscle mass represents a smaller proportion of total

weight, and creatinine production is decreased.
Because M.C. is a 65-year-old woman, a creatinine clearance (Cr.Cl.) determination
would more accurately reflect her renal function status
Decrease the
dose to half a
tablet per day
Urine analysis
freshly produced, urine is
normally mostly acidic (pH
4.6–8).

an aged
specimen
But what if aged sample ??
 Urivin®
alkalization
sodium
bicarbonate

Epimag®
Magnesium
Citrate
Effervescent
Microbiology Testing
 Microbiology Testing
• Sample • Microorganism/ Infection
• Type of specimen ( blood, CSF, • Type of microorganism (MDR or not)
Urine,……)
• Local vs systematic infection (severity)
• Sampling procedure (aseptic
technique esp. urine analysis) • Patient immunity status
• Timing before or after treatment
(diagnostic or prognostic)
• On any antibiotics before sampling • Patient
• Patient immunity status
• Antibiotic
• Age
• Sensitivity to M.O
• Kidney and liver function
• Bioavailability to tissue
• CSF culture and sensitivity in normal
renal/hepatic patient.
• Micro organism is Klebsiella pneumoniae
sensitive to:

zone
• Piperacillin-tazobactam S 25 Ciprofloxacin
S 25 Levofloxacin S 23
Imipenem S 25
Meropenem S 25
Amikacin s 23

• Which one should you choose?

• CSF culture and sensitivity in normal renal/hepatic
patient.
• Micro organism is Klebsiella pneumoniae sensitive to:

zone
Reference zone
• Piperacillin-tazobactam S 25 S≥
• Ciprofloxacin S 25 21
• Levofloxacin S 23 21
• Imipenem S 25 17
• Meropenem S 25 23
23
• Amikacin s 23
17

• Which one should you choose?

1-Levofloxacin, Amikacin
2-Piperacillin-tazobactam & Ciprofloxacin
3-Imipenem & Meropenem
 Priority acc. to most sensitive
1-Levofloxacin,Amikacin
2-Piperacillin-tazobactam & Ciprofloxacin
3-Imipenem & Meropenem

Priority acc. to most sensitive Priority acc. to most sensitive

1-Levofloxacin, Amikacin 1-Levofloxacin,Amikacin
2-Piperacillin-tazobactam & 2-Piperacillin-tazobactam &
Ciprofloxacin Ciprofloxacin
3-Imipenem & Meropenem 3-Imipenem & Meropenem
 Useful resources
• https://labtestsonline.org/

• A manual of laboratory and diagnostic tests ninth edition

• https://play.google.com/store/apps/details?id=co
m.mdaware.mdcalc

• https://play.google.com/store/apps/details?id=co
m.qxmd.calculate

• https://play.google.com/store/apps/details?id=co
m.halcyonmobile.medicalthreeinone
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