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Medical Laboratory Tests for the Optometrist

Tracy Doll, OD

 

Contents

Introduction

A working knowledge of basic medical laboratory testing can be crucial in the event that a systemic condition or infection is a suspect etiology of an ocular finding. The correct diagnosis and appropriate referral to another health care provider can depend entirely on the results of a laboratory test.  This paper discusses indications for laboratory tests that are most useful for optometry, including hematology, blood chemistry, urinalysis, serology, the PPD, and cytology and how to interpret their results.

Optometrists should always communicate with the patient’s primary health care provider when considering requesting a medical laboratory test.  Primary health care providers may often provide useful information regarding the patient’s health history and can often recommend other useful tests to order.  When in doubt of which medical laboratory test to request, always consult with a primary care physician.

Blood Work

Blood work consists of three categories: hematology, blood chemistry, and serology.  The differences between these is described below:

Hematology

Hematology, the study of blood and its components, can be broken down into three specific test groupings which will be discussed in detail:

 

The Eight Components of the Complete Blood Count:

Red Blood Cell Count (RBC)

The RBC count tells the clinician the number of erythrocytes per cubic millimeter (mm3 or µL). Normal ranges for a CBC can be seen in Table 1 below (1).

When the RBC count is below the normal range, the patient is diagnosed with anemia. Anemia can be caused by blood loss, iron or vitamin B12 deficiency, or bone marrow dysfunction.  Conversely, when the RBC count is above the normal, called polycythemia, it may be due to ominous causes like leukemia (2).  Both anemia and polycythemia can lead to cotton-wool spots and/or hemorrhages on the retina: including white centered retinal hemorrhages (Roth Spots), mid-peripheral or peripheral retinal hemorrhages (3).

Hemoglobin (Hb)

Recall that hemoglobin (Hb) is the iron-containing protein that carries oxygen in the bloodstream, as part of the RBC. Therefore, anemic conditions that reduce RBC count also reduce Hb levels. Polycythemic conditions, like leukemia, can likewise elevate Hb levels, as can lung disease. Elevated Hb levels are expected for patients who live at high altitudes, and might also be seen in smokers (2). The normal range for Hb can be seen in Table 1.

Hematocrit (HCT)

HCT is also called the packed cell volume, and tells the clinician the percentage of the blood volume occupied by red blood cells. The normal percentage of HCT is 42-52% of blood volume for men and 37-47 % for women (1). Low HCT levels could mean the patient has anemia.

 Higher HCT is associated with a disease called polycythemia vera (2). Polycythemia vera is a myeloproliferative disorder that causes all of the red blood cell elements in the blood to be over-produced. A stem cell defect is the theorized cause of this disorder. This rare condition usually occurs in the sixth decade of life and most commonly affects Caucasian females of Jewish descent (2).

Systemic symptoms of polycythemia vera are a result of the increased red blood cell mass in the blood: headache, pruritis (itching), fatigue, and weight loss. The pruritis is exacerbated by heat (showering or exercising) due to the increased amount of histamine from the red blood cells. Ocular signs of polycythemia vera can include retinal vein thrombosis and occlusions, in addition to cotton wool spots (3). Eventually 5-10% of patients with polycythemia vera will develop acute leukemia (2).

Mean Corpuscular Volume (MCV)

 

The average size of red blood cells is measured by the MCV.  A low MCV can indicate that the patient has iron deficiency anemia, while high MCV suggests vitamin B12 deficiency (pernicious anemia). Overall, MCV is used to help diagnose anemia, but it call also occur with recent blood loss, or poor bone marrow function, or folic acid deficiencies (2). Normal levels for the MCV is 80-90 fL (femtoliters) (1).

Folic acid plays a crucial role in DNA synthesis, including the DNA of rapidly dividing cells. Erythrocytes, leukocytes, and platelet formation will be affected in folic acid deficiency, resulting in abnormal cells.  Vitamin B12 aids folic acid in DNA synthesis. Thus, a B12 deficiency can also interfere with normal blood cell formation. It can result in an elevated MCV, called macrocytic anemia (2).

Mean Corpuscular Hemoglobin (MCH)

The MCH is a test of the mass of the hemoglobin present in an average red blood cell.  The normal range for MCH is 27-31 picograms (see Table 1). Both low (hypochromic) and high (hyperchromic) MCH values can be consistent with anemia. Hyperchromic anemias include folic acid or vitamin B12 deficiency.  Hypochromic anemias include iron deficiency and a disease known as thalassemia (3).

Thalassemia is a family of congenital disorders that cause decreased production of normal hemoglobin in red blood cells. Abnormal hemoglobin can lead to anemia, spleen disease, infections, gallstones and bone deformities (most common in the face) (2).

 

Platelet Count (PLT)

Platelets, once called thrombocytes, are necessary for blood clotting and repairing damaged blood vessels. A normal platelet count is between 150,000- 400,000 platelets/mm3 (see Table 1).

Expect PLT values to be elevated with chronic bleeding such as gastric ulcers, in patients who smoke, or those with leukemia. Expect reduced PLT values from autoimmune thrombocytopenia (resulting in the destruction of RBCs), blood loss, due to anticoagulant medication side effects, like Warfarin (Coumadin).  A low PLT can also indicate disease such as an enlarged spleen, septicemia, bone marrow failure due to leukemia, or a condition called myelofibrosis (2,3).

In myelofibrosis red blood cells have unregulated proliferation.  The platelets that are formed are giant, irregular or fragmented and cannot function normally (2,3).

Mean Platelet Volume (MPV)

The MPV can tell the clinician the average size of the platelets in a patient’s bloodstream.  Normal platelet volume is 7-11 fL (Table 1).

Decreased MPV is consistent with diseases like aplastic anemia. Recent research has shown that a low MPV can also be associated with inflammatory bowel diseases, and high MPV may be an independent risk factor for transient ischemic attack (stroke) and myocardial infarction (3).

An elevated MPV can also indicate idiopathic thrombocytopenic purpura. Thrombocytopenia purpura is a blood disorder found in young children, two to four years old. The destruction of platelets in this disorder is often followed by upper-respiratory infections.  The cause of this disorder is unknown, but causes children to easily bleed. This condition often will spontaneously go into remission.  A more chronic form of this condition can also occur (2).

 

White Blood Cell Count (WBC)

WBC count is the number of leukocytes per cubic millimeter (mm3 or µL). A normal WBC count is 4,000-10,000/ mm3 (Table 1). A low WBC count is called leukopenia. Infection will classically show the clinician an elevated WBC count. Leukemia (bone cancer) will grossly raise WBC count as well (3)

Ocular signs of leukemia include white-centered retinal hemorrhages (Roth Spots) flame hemorrhages and mid-peripheral retinal hemorrhages (75).

Table 1: Blood Components

Complete Blood Count Component

Normal Adult Value Nice

 

Red Blood Cell (RBC) Count

Men:     4.7-6.1 million cells/uL

Women: 4.2-5.4 million cells/uL

Hemoglobin (Hb)

Men: 14-18g/dL or 8.7-11.2 mmol/L

Women: 12-16 g/dL or

               7.4-9.9 mmol/L

Hematocrit (HCT)

Men:      42-52%

Women: 37-47 %

Mean Corpuscular Volume (MCV)

80-90 fL (femtoliters/µ3)

Mean Corpuscular Hemoglobin (MCH)

27–31 picograms (pg)

Platelet Count (PLT)

150,000- 400,000 platelets/mm3

Mean Platelet Volume (MPV)

7-11 fL (femtoliters)

White Blood Cell (WBC) Count

Men: 5,000-10,000 wbc/mcL3

Women:4,500-11,000 wbc/ mcL3

Source: http://www.webmd.com/a-to-z-guides/complete-blood-count-cbc?page=3

Note that all medical laboratory equipment and hospitals may use different criterion for the norms of the laboratory testing values (though they are always similar).  These norms are known as “reference” values. If a test value is outside of the reference numbers, the laboratory test will be flagged with an “L” for lower than normal values and an “H” for higher than normal values. Table 2 below shows an example of a printout for a complete blood count with differential test.

Table 2: Example of CBC with Differntial Medical Laboratory Print Out Southwest Washington Medical Center Test Patient

 
Complete Blood Count With Differential Components

A complete blood count should always be ordered with a differential component because it implies which type of immune response is occurring and give clues to underlying pathology including infection, autoimmune disease, blood disorders, and allergies.

Differential blood count (Diff) divides white blood cells into five different types.  They are (in order of incidence): 

  1. Neutrophils: These white blood cells work like a “vacuum cleaner”, by phagocytizing microorganisms or particles. A higher than normal number of neutrophils are most often due to bacterial infection, but can also arise from arthritis, surgery, trauma, or myocardial infarction. Myeloproliferative disorders are a less likely cause (2,3).
  2. Lymphocytes: these white blood cells make antibodies bind to pathogens to coordinate the immune response.  They come in three varieties: Cytotoxic (“Killer”), T-cells and B-cells.  Expect them to be elevated in patients with viral infections, active allergies and toxic reactions like food poisoning. The lymphocyte count will be depressed in HIV positive patients, as the disease selectively attacks and destroys the Helper T-cells (2,3).. Isolated retinal cotton wools spots can be seen in HIV infection (75).
  3. Monocytes fight infection by phagocytizing dead or damaged cells and pathogens not fought off by neutrophils or leukocytes. A high count can indicate systemic bacteria, as in septicemia (3)..
  4. Eosinophils: seen in response to allergies, parasitic infections, collagen vascular disease and other extensive skin diseases, as well as Addison’s Disease. In the latter case, this is called eosinophilia (2,3).
  5. Basophils: this fifth type of white blood cell brings about allergic response to antigens, mainly by releasing histamine to cause inflammation.  Low numbers of basophils may precede the onset of leukemia (2,3)
Table 3: White Blood Cells

White Blood Cell Type

Normal Values

% of total WBC count

Appearance

Neutrophil

48 -80k/ mm3

40% to 60%

 

Image:Neutrophil.png

Lymphocyte

21-47k / mm3

20% to 40%

 

A stained lymphocyte surrounded by red blood cells viewed using a light microscope

Monocyte

4 -8k / mm3

2% to 8%

Eosinophils

0-0.70k/ mm3

1% to 4%

Basophils

0-0.20k / mm3

0.5-1%

Source: 4,5

Please note again, that “normal values” or “reference values” will vary slightly from test instrument to test instrument.  Table 4 shows the laboratory print out with reference ranges.  Note that the printout includes the norm for the percentage of total WBC count.

Table 4: Examples of CBC Differential of White Blood Cells

Medical Laboratory Print Out: Southwest Washington Medical Center Test Patient

 

Erythrocyte Sedimentation Rate (ESR or sed rate)

Abnormal blood plasma proteins from inflammatory disease stick to red blood cells and cause them to settle to the bottom of a blood sample more quickly. The height of the RBC’s, in mm, settled out of plasma per hour is called the erythrocyte sedimentation rate (ESR) (2).     

The ESR test has excellent sensitivity but low specificity.  In other words, it can detect even subtle inflammation, but cannot tell the clinician which disease state is responsible (3). ESR is elevated in inflammatory conditions including systemic lupus erythematosus, rheumatoid arthritis, tuberculosis, myocardial infarction, polymyalgia rheumatica and hepatitis C, in addition to temporal giant cell arteritis (GCA) (3).

If the patient is a suspect for GCA, the first blood test the clinician should order is an ESR (75).  Signs and symptoms of GCA include: optic neuritis, positive afferent pupillary defect, vision loss, temporal headache, jaw claudication (muscular pain when chewing) and scalp tenderness. A temporal artery biopsy should also be immediately ordered if temporal arteritis is strongly suspected. The biopsy may be ordered while lab results are being processed.  Sometimes, both tests are needed because one test may have equivocal results.

The maximum normal ESR for men is equal to the patient’s age divided by two. The normal maximum ESR for women is equal to (age + 10) divided by two (3,6).   A sedimentation rate greater than 50 mm/hr is suggestive of inflammation.  Always order a CBC with an ESR, as anemia can falsely increase the ESR. The Westergren ESR type is more commonly used (2).

The Erythrocyte Sedimentation Test

A rack of ESR tubes.

Source: 6

 

C- Reactive Protein (CRP)

Another marker of inflammation is C-Reactive Protein.  This plasma protein rises dramatically in systemic inflammation. In addition to CRP being an indicator of acute inflammation, it can also be elevated in stress, trauma, surgery, neoplastic infection or myocardial infarction (7).

Clinicians use the CRP to check for inflammatory flare-ups, or to monitor the effectivity a specific treatment regimen. Note that the CRP level is not always elevated by inflammation, thus this test has some false negatives.  When it is elevated, CRP levels have been associated with increased risk for diabetes, hypertension and cardiovascular disease (7). Patients with CRP levels of less than 1mg/L are considered low risk, while levels of greater than 3mg/L are considered high risk for cardiovascular disease (76). The role of CRP in coronary artery disease is still being investigated.  It is possible that the CRP is not merely a marker of inflammation, but instead plays an active role in inflammatory disease (3).