Lecture 4
Lab test analysis
By
Dr/ Asmaa Ahmed Hamed
Pharmacists have a key role in selecting appropriate laboratory
tests for TDM,
interpreting tests to determine whether a drug is producing its
desired therapeutic effect,
And avoiding adverse drug effects
Pharmacists should be familiar with useful references to help
interpret and apply lab test results to particular patient situations,
so that
they can make appropriate recommendations for altering drug
therapy.
Pharmacists with an appreciation of the role of clinical laboratory
testing in patient care can perform a valuable service for their
patients and other health professionals.
Laboratory tests can provide useful information for clinicians for the
diagnosis of a medical condition and for the monitoring of drug
therapy (e.g., effect of an antibiotic therapy for a bacterial infection
As a pharmacist, laboratory values can help select the most safe
and appropriate therapy for patients, in addition to aid in the
monitoring of the selected therapy. For instance, serum creatinine
is a laboratory value used to estimate the patient’s renal function
by calculating creatinine clearance
This information is useful for adjusting the dose of certain
medications cleared through the kidneys, such as digoxin.
In patients with renal insufficiency, decreased renal
excretion of digoxin can lead to increased risk of digoxin
toxicity, and as a result, patients may benefit from a dose
reduction of digoxin based on creatinine clearance
Although laboratory errors are fairly uncommon, they do
occur. Potential causes could include technical errors,
sample contamination, timing in which the lab value was
taken, i.e. trough levels should be drawn just prior to the
next dose, and medication interference, If any laboratory
error is suspected, the test should be repeated
Electrolytes
1. Sodium
Sodium is the most prevalent extracellular cation in the
body. Its primary function is to regulate the serum
osmolality, fluid balance, and acid base balance.
Measuring serum sodium values helps in assessing the
patient’s electrolyte, water, and acid base balance. It also
helps assess their renal function.
Normal values: 135-145 mEq/L.
Clinical Significance
An increased level of sodium (hypernatremia) often
occurs as a result of dehydration or fluid loss, which could
be due to conditions such as gastroenteritis, diarrhea, or
Cushing’s syndrome.
Conversely, hyponatremia is often due to edema from a
relative increase in free body water. Certain drugs, like
tricyclic antidepressants and loop diuretics, could
potentially cause hyponatremia.
2. Potassium
Potassium is the main intracellular cation and
plays a key role in many bodily functions including
nerve excitability, acid base balance, and muscle
function.
Normal values: 3.5-5 mEq/L.
Clinical Significance
An increase in potassium (hyperkalemia) could be due to metabolic
or respiratory acidosis, or renal failure.
Certain drugs, like angiotensin converting enzyme inhibitors (ACEIs)
and potassium sparing diuretics, may elevate potassium.
Potassium is typically monitored at baseline, and after a few weeks
of starting therapy.
Meanwhile, the reasons for hypokalemia could include severe
diarrhea, respiratory alkalosis, and use of drugs, such as loop and
thiazide diuretics as well as osmotic diuretics, like mannitol.
3. Chloride
Chloride is the principal extracellular anion which functions to
serve a passive role in the maintenance of fluid balance and acidic
base balance, by having an inverse relationship with bicarbonate.
Normal values: 96-106 mEq/L.
Clinical Significance Any deviations in normal values are a sign
of fluid or acid base balance disorder, such as metabolic acidosis,
respiratory alkalosis, or prolonged vomiting.
Blood Glucose
Glucose is an important source of energy for most cellular functions, and its regulation is achieved
through a complex mechanism comprising insulin, glucagon, cortisol, adrenaline, and other
hormones.
Normal values: Fasting blood glucose:
(70-99 mg/dL).
2 hours glucose tolerance test
Less than 140 mg/dL (7.8 mmol/L) is normal
Clinical Significance High levels of glucose may be detected in patients with Type I, Type II, or
gestational diabetes, and are commonly used as a diagnosis of diabetes or pre-diabetes.
It is also used as a monitoring tool to monitor the diabetic control of a patient, both for routine
monitoring and self-monitoring.
Hematology
Full Blood Count
The full blood count provides values for hemoglobin (Hb) and
hematocrit (Hct) (to detect anemia), red blood cell (RBC) count, white
blood cell (WBC) count, WBC differential count, and RBC morphology.
There are some subtle differences in values between males and
females for these measurements, and these need to be taken into
consideration when interpreting the values.
1. Hemoglobin
Hemoglobin is the oxygen-carrying compound in the RBCs and is a
direct indicator of the oxygen-carrying capacity of blood. Normal
values:
Male: 14-18 g/dL
Female: 12-16 g/dL
Clinical Significance
Increased Hb levels can be due to diseases such as chronic pulmonary
lung disease or polycythemia vera. It may also be increased in chronic
smokers, those who live at high altitudes (due to low oxygen in air at
higher altitudes), and those who engage in regular exercise. The high
carbon monoxide content in cigarette smoke prevents oxygen from binding
to Hb, making the body interpret low Hb levels, and signal for increased
RBCs production.
Conversely, lower levels are an indication of anemia or hemorrhage.
2. Hematocrit:
Hematocrit, also known as packed cell volume, describes the volume of
blood occupied by RBCs. It can also be used as an indicator of Hb, as
hematocrit values are usually three times the value of Hb. Normal values:
Male: 39%-49% ,
Female: 33%-43%
Clinical Significance: Similar to Hb, decreased values are an indication of
anemia or hemorrhage. The hematocrit can indicate if there is a problem
with RBCs, but it cannot determine the underlying cause.
3. Red Blood Cell Count:
RBCs serve to transport oxygen from the lungs to the body tissues. They have a
life span of approximately 120 days, before being cleared by the
reticuloendothelial system. In most laboratory reports, the results will examine
the number of cells per cubic mm, size, shape, color, maturation, and content.
These can then be used to classify different types of anemia to pinpoint the
etiology. In general, they can be classified by the following:
RBC size or mean corpuscular volume (indicating average RBC size).
RBC color or mean corpuscular Hb concentration, which can be hypochromic,
hyperchromic, and normochromic.
For example, microcytic, hypochromic anemia could be due to iron
deficiency.
Normal values:
Male: 4.3-5.9 x 106 cells/mm3 or 4.3-5.9 x 1012 cells/L.
Female: 3.5-5.0 x 106 cells/mm3 or 3.5-5.0 1012 cells/L.
Clinical Significance
An increased level of RBCs is usually associated with polycythemia vera, stress,
chronic smoking, and living at high altitudes. Low RBC counts can be due to
anemia, hemorrhage, or chronic renal failure. Low levels of iron causes iron
deficiency anemia, folic acid deficiency causes megaloblastic anemia, B-12 vitamin
deficiency causes pernicious anemia, and pyridoxine or copper deficiency causes
sideroblastic anemia.
Long term use of the oral hypoglycemic agent, metformin, has been linked with
vitamin B12 deficiency.
4. White Blood Cell Count:
WBCs, or leukocytes, consist of five main types: neutrophils, lymphocytes,
monocytes, eosinophils, and basophils. The WBC count is usually given with a
breakdown of the percentage of each WBC type. WBCs protect the body against
foreign bodies and infection.
Neutrophils are the most abundant WBCs.
Normal values: 3.2-11.3 x 109 cells/L.
Clinical Significance
An increase in WBC count (leukocytosis) is suggestive of an invading
organism. In general, the most commonly observed readings are the
lymphocyte counts, as these are usually an indicator of viral infections.
Meanwhile, an increase in eosinophil levels is taken to be
associated with allergic reactions and parasitic infections. Neutrophil
levels may rise due to drugs like steroids, infection, or intense exercise.
5. Platelets:
Platelets are a critical element of blood clot formation. They bind together when
damaged blood vessels are recognized. Normal values: 150,000-450,000/mL.
Clinical Significance
High levels of platelets (thrombocytosis) can be caused by infections and chronic
inflammatory disorders, as well as iron deficiency anemia.
Decreased platelet counts (thrombocytopenia) may occur in patients with an
autoimmune disorder, or while under chemotherapy, due to bone marrow
suppression.
Heparin can also cause an idiosyncratic reaction of low platelet counts called
heparin-induced thrombocytopenia.
6. Prothrombin Time:
A fundamental understanding of the coagulation pathway is imperative in
interpreting prothrombin time (PT). The PT is a measure of the integrity of the
extrinsic and final common pathways of the coagulation cascade.
It consists of tissue factor and factors II (i.e., prothrombin), V, VII, X, and
fibrinogen. The test is performed by the addition of calcium and thromboplast, an
activator of the extrinsic pathway, to the blood sample; then, the time (in seconds) is
measured for the formation of fibrin clot.
Normal values: 9.5-13.5 seconds.
7. International Normalized Ratio:
The international normalized ratio (INR) is a standardized method of
reporting the effects of oral anticoagulants, such as warfarin, on blood clotting.
This test is commonly performed in individuals receiving warfarin, to ensure the
dose is sufficient to prevent thrombosis, and to minimize the risk of bleeding.
The INR is derived from prothrombin time (PT) which is calculated as a ratio
of the patient’s PT to a control PT
Normal values: The reference range for INR should be less than 1.3.
Patients are monitored every 3–4 weeks
Clinical Significance
There are various conditions that may affect PT and INR. Some of the
causes of a prolonged PT include anticoagulant therapy (e.g., warfarin).
Vitamin K deficiency can elevate the INR, and may occur due to malnutrition,
biliary obstruction, malabsorption, use of certain broad-spectrum antibiotics,
liver diseases (i.e., synthesis of clotting factors is diminished), fibrinogen
abnormalities (e.g., hypofibrinogenemia, afibrinogenemia,
dysfibrinogenemia), or dilution of plasma clotting proteins after a blood
transfusion.
Examples of antibiotics that may interact with warfarin, and alter the INR,
include cephalosporins, metronidazole, macrolides, fluoroquinolones,
penicillins, sulfonamides, and tetracyclines. Furthermore, azole antifungals are
most likely to increase bleeding risk in older continuous users of warfarin.
A decreased PT can be caused by vitamin K supplementation, high intake of
food containing vitamin K (e.g., liver, broccoli), estrogen-containing drugs (e.g.,
contraceptive pills), and freshly frozen plasma transfusion. Patients on warfarin
therapy should be counseled regarding major changes in vitamin K rich food,
like green leafy vegetables, and its affect on PT/INR.
8. Partial Thromboplastin Time and Activated Partial
Thromboplastin Time
A test similar to the PT, the partial thromboplastin time (PTT) and
activated partial thromboplastin time (aPTT), is performed to detect
clotting abnormalities. The aPTT is similar to PTT, but an activator is
added to speed up the clotting time, thus rendering it more
sensitive than PTT due to the narrow range.
Normal values: 60-70 seconds for PTT; 30-45 seconds for aPTT
(depending on methods).
Clinical Significance
A prolonged PTT or aPTT may indicate congenital deficiencies of intrinsic system
clotting factors such as factors VIII, IX, XI, and XII including hemophilia A and
hemophilia B (Christmas disease), an inherited bleeding disorder, Von Willebrand
disease (which affects platelet function owing to decreased Von Willebrand factor
activity).
Liver cirrhosis, vitamin K deficiency, and heparin therapy may also prolong PTT or
aPTT.
Early stages of disseminated intravascular coagulation, extensive cancer, such as
ovarian, pancreatic, or colon cancer, or an acute-phase response leading to high
factor VIII levels, may lead to a decreased PTT or aPTT.
There are also some factors that may interfere with the aPTT test. These
could be a drug, such as antihistamines, chlorpromazine, heparin, and
salicylates, or other factors such as blood samples drawn from the heparin
lock or a heparinized catheter.
