Interpreting Clinical Lab Data

M.ABD ELAZIZ, PhD, MD

Professor of clincal pharmacology

Mansoura University

GENERAL PRINCIPLES

Generally, laboratory tests should be ordered only

1-if the results of the test will affect decisions about the care of the patient.

2- The serum, urine, and other bodily fluids can be analyzed routinely;

3-however, the economic cost of obtaining these data must always be balanced by benefits to patient outcomes.

Normal Values 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.” Laboratory findings, both normal and abnormal, can be helpful in Assessing: clinical disorders, establishing a diagnosis, assessing drug therapy, or evaluating

disease progression . In addition, baseline laboratory tests are often necessary to evaluate disease

progression and response to therapy or to monitor the development of toxicities associated with therapy.

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.

Laboratory Error Avariety of factors can interfere with the accuracy of laboratorytests. 1- Patient-related factors (e.g., age, gender, weight,height, time since last meal) can affect the range of

normal values for a given test. 2- Laboratory-based issues can also influence the accuracy of laboratory values. For example, a specimencan be spoiled A-because of improper handling or processing (e.g., hyperkalemia due to hydrolysis of a blood

specimen); B-because it was taken at a wrong time (e.g., fasting blood glucoselevel taken shortly after a meal); C- because collection was incomplete (e.g., 24-hour urine collection that does not span a full 24-hour

period); 3- Errors also can arise due to faulty poor quality reagents (e.g., improperly prepared, outdated); 4-due to technical errors (e.g., human error in reading result, computer-keying error); 5- due to interference from medical procedures (e.g., cardioconversion increases creatine kinase [CK] serum concentrations); 6-due to dietary effects (e.g., rare meat ingestion can cause a false-positive guaiac test); 7- 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).

8-Clinicians might not be aware of when laboratory-related issues arise. 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.

  Side A  Side B       Side A  Side B 

1.aden/o  gland    11.carcin/o  cancer 

2.cardi/o  heart    12.chem/o  chemical 

3.cis/o  to cut    13.dermat/o  skin 

4.enter/o  small intestines    14.gastr/o  stomach 

5.gynec/o  female    15.hemat/o  blood 

6.hydr/o  water    16.immun/o  immun 

7.laryng/o  voice box    17.morph/o  shape 

8.nephr/o  kidney    18.neur/o  nerve 

9.ophthalm/o  eye    19.ot/o  ear 

10.path/o  disease    20.pulmon/o  lung 

Interpreting Clinical Lab Data

Objectives:1. Identify the characteristics and function of each

type of leukocyte.2. Identify the significance of comparing the WBC

count to the neutrophil count in patients with pneumonia.

3. Identify common causes for increases and decreases in the neutrophil count.

4. State how the “rule of three” is useful for interpretation of the RBC count and indices.

Divisions of the Clinical Lab

Hematology– Complete blood count

• WBC count• Platelets• RBC count

Chemistry– Electrolytes

• Potassium• Sodium• Total CO2• Chloride

Divisions of the Clinical Lab

Microbiology– Sputum gram stain– Sputum culture and sensitivity– Pleural fluid culture and sensitivity

Blood Bank- blood typing and storage

CELL MORPHOLOGY

Cell Morhphology (neutrophil)

Segmented neutrophil (40-70% of WBCs)

Life span of about 10 days

Moves from bone marrow to blood to tissues

Mature more quickly under stressful conditions

Primary defense for bacterial infections

Cell Morhphology (neutrophil)

The Neutrophil

Once in the peripheral blood, it can be in the circulating pool (CP) or the marginated pool (MP) (approx. 50%)

cells in MP not counted in CBCShift from the MP to the CP can occur with

stress, trauma, catecholamines, etc.This results in a transient leukocytosisSuch leukocytosis can last 4 to 6 hours

The Neutrophil

Present in band and segmented formsBands make up < 5 % of circulating

neutrophils normally“Left shift” is seen as an increase in the

number of bands and is common with acute infection

Main function is to locate, ingest, and kill bacteria and other foreign invaders

Cause of Neutrophilia

Pathologic– Bacterial infection

– Certain viruses and fungi

– Inflammatory responses to tissue death• Burns

• Snake bites

Drugs– steroids

– lithium

Causes of Neutrophilia (cont.)

Physiologic– Pseudoneutrophilia (shift of cells from the MP

to CP)• Catecholamines

• Acute stress

Other inflammatory responses– Neoplastic growth– Metabolic disorders

Pools of Neutrophils

1. Bone marrow: many banded forms are present; neutrophilia with lots of bands suggest bone marrow was source

2. Circulating Pool: used to deal with day to day invasion of the body by organisms

3. Marginated Pool: no bands; respond to physiologic stimulation

Causes of Neutropenia

Decreased Production of WBCs– bone marrow diseases– malignancies that affect the bone marrow

Increased Neutrophil Destruction– overwhelming infection– certain bacteria– immune reactions

Pseudoneutropenia (shift of cells from CP to MP)– viral infections– hypothermia

Cell morphology (Eosinophil)

Segmented eosinophilLife span = 14 daysSpends little time in the

blood before it locates in the skin, GI tract, or respiratory tract

Only 1% of mature cells are located in blood

The Eosinophil

Also function as phagocytes but appear to be less potent than neutrophil

Drawn to sites of hypersensitivity reactions by mast cell chemotactic factors

Often found in sputum of asthmaticsMay play a role in pathogenesis of lung dzPlay a role in parasitic infections

The Basophils

Mature basophilLeast common of

WBCs (< 2%)Nucleus does not

always segment Increase in response

to same conditions that cause eosinophils to respond

The Monocytes

Also not common in circulating blood

Stay in blood for about 70 hours

Become macrophages in tissue and live for several months or longer

The Monocytes

Primary role is phagocytosisPlay large role in ingesting cellular debrisBecome “activated” when direct contact

with microorganisms occursActivated cell has greater motility, enzyme

activity and killing capacity (causes fever)Also play a role in immunity

The Lymphocytes

May mature into B or T cells

Main function is antigen recognition and immune response

Life span quite varied (up to two years)

Can pass back and forth between blood and tissues

Lymphocytes: B & T types

B cells are not only produced in the bone marrow but also mature there.

However, the precursors of T cells leave the bone marrow and mature in the thymus (which accounts for their designation)

Types of Lymphocytes

B lymphocytes (or B cells) are most effective against bacteria & their toxins plus a few viruses

T lymphocytes (or T cells) recognize & destroy body cells gone awry, including virus-infected cells & cancer cells.

T cells come in two types: helper cells and suppressor cells; normally the helper cells predominate.

Lymphocyte Count: Decreased

I. Decreased A. AIDS B. Bone Marrow suppression C. Aplastic Anemia D. Steroids E. Neurologic Disorders 1. Multiple Sclerosis 2. Myasthenia Gravis

3. Gullain Barre Syndrome

Lymphocyte count: Increased

a. Influenza

b. Pertussis

c. Tuberculosis

d. Mumps

e. Cytomegalovirus Infection

f. Infectious Mononucleosis

g. Infectious Hepatitis

h. Viral pneumonia

Interpreting the CBC

What is total white cell count?If elevated (>11,000), what type of WBC

is the culprit?Is it the neutrophils, eosinophils,

lymphocytes, basophils, or monocytes?Marked leukocytosis is usually due to

neutrophils or lymphocytes.

Interpreting the CBC

Normal Values

% Absolute

Neutrophils 40 – 70 1800 – 7500

Eosinophils 0 – 6 0 – 600

Basophils 0 – 1 0 – 100

Lymphocytes 20 – 45 900 – 4500

Monocytes 2 – 6 90 - 1000

Interpreting the CBC

If the neutrophils are causing the leukocytosis, compare the neutrophil % to total WBC.

The % neutrophils indicates the severity of the infection; the total WBC reflects the quality of the immune system

Interpreting the CBC (Case # 1)

85 yr old female with pneumonia:

Total WBC is: 11,500

Neutrophil % = 80% (9200) bands = 5%

This indicates that a severe infection is present but the immune system is unable to respond appropriately.

Prognosis poor.

Interpreting the CBC (Case # 2)

5 yr old male with pneumonia

WBC = 18,000

Neutrophils = 60% (10,800)

Marked leukocytosis and normal range for neutrophils indicates moderate infection but excellent immune system response

Excellent prognosis

Interpreting the CBC (Case #3)

10 yr old male admitted for pneumonia:

WBC: 16,000

neutrophils = 75% (12,000) (1800-7500)

Bands = 5% (800) (0-100)

Eosinophils = 1% (160) (0-600)

Lymphocytes = 10% (1600) (900-4500)

Basophils = 0% (0) (0-100)

Monocytes = 3% (480) (90-1000)

Interpreting the CBC (Case #3)

Interpretationneutrophilia probably due to bacterial

pneumonialeft shift indicative of severe infection the source of the neutrophils is the bone

marrow since many bands are present

Case Study # 4

20 yr old male admitted following MVA

WBC 14,500 75% neutrophils 1% bandsLeukocytosis due to neutrophiliaHistory and low per cent of bands suggest

pseudoneutrophiliaDue to liberation of marginated neutrophils

in the intravascular system

Interpreting the CBC

What is indicated by leukopenia?

1. Bone marrow failure

cancer e.g. leukemia, lymphoma

2. Overwhelming infection

severe pneumonia pt who has poor immune system and can’t produce enough WBCs

3. Shift of neutrophils to MNP (viral infections and hypothermia)

Platelet Count

Normal count is 140,000 to 440,000/mm3Life span of about 10 daysLow platelet counts (thrombocytopenia)

cause excessive bleedingThrombycytopenia is common with the use

of heparin, DIC, bone marrow disease, liver failure and sepsis

Platelet

Platelet (Activated)

  

                                                         

Side A Side B Side A Side B

1.aden/o gland 11.carcin/o cancer

2.cardi/o heart 12.chem/o chemical

3.cis/o to cut 13.dermat/o skin

4.enter/o small intestines 14.gastr/o stomach

5.gynec/o female 15.hemat/o blood

6.hydr/o water 16.immun/o immun

7.laryng/o voice box 17.morph/o shape

8.nephr/o kidney 18.neur/o nerve

9.ophthalm/o eye 19.ot/o ear

10.path/o disease 20.pulmon/o lung

22.a , without, away from

27.an without

23.ante before, in front of

28 .anti - ,against

24.auto ,self 29 .brady slow

25.dys - painful, difficult

30 .endo ,within, inner

Red Blood Cells

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

Interpreting the RBC count

1. Normal values:Men: 4.2 – 5.4 million/mm3

Women: 3.6 – 5.0 million/mm3

2. Anemia – abnormal Decrease in RBC count

- decreased production

- increased destruction (hemolysis)

- blood loss

Interpreting the RBC count

3. Increased RBC count = Polycythemia

A. Primary

B. Secondary

living at altitude

chronic lung/heart disease

tobacco use/carbon monoxide

C. Relative Polycythemia

dehydration

Red Blood Cell Indices

Mean Corpuscular Volume (MCV)– Volume occupied by a single RBC– Increase in MCV is known as Macrocytic anemia.– Decrease in MCV is known as Microcytic anemia.

Mean Corpuscular Hemoglobin Concentration– (MCHC)– Measure of the concentration of hemoglobin in an

average RBC– Decrease in MCHC is known as Hypochromic anemia– Normal is known as Normochromic anemia.

Red Blood Cell Indices

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

Red Blood Cell Indices

Hematocrit

The RULE of Three

Applies to normocytic, normochromic erythrocytes only

Useful to detect laboratory error in measuring the Hb, HCT, and RBC count

3 times the RBC count should = Hb3 times Hb should = Hct

RBC = 3.0 x 1012 3 x 3 = 9

Hb = 9.2 g/dL 3 x 9.2 = 27.6

Hct = 28%

The RULE of Three

Interpreting the Red Blood Cells

CBC: Results Normals

RBC (x1012/L) 4.2 4.2-5.4

Hgb (g/dL) 10.6 11.5-15.5

Hct 34.9% 38%-47%

MCV (m3) 77.0 80-96

MCHC 30.4% 32-36%

Interpretation: Microcytic, hypochromic anemia; rule of 3 does not apply

Reticulocyte Count

Normal values: – 0.5 – 1.5% of RBC

Helpful to identify cause of Anemia

Increase indicates Anemia is due to Blood loss

Decrease indicates Anemia is due to Bone marrow disease

Bibliography

Steine-Martin: Clinical Hematology, 2nd edition, Lippincott, Philadelphia, 1998.

Kaplan: Clinical Chemistry, 4th edition, Mosby, St. Louis, 2003.

Wilkins: Clinical Assessment in Respiratory Care, 5th edition, Mosby, St. Louis, 2005.