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Explain the tests: Complete blood cell count (CBC) – White blood cell count (Part five)

White blood cells, also called leukocytes, are key functionaries of the immune system.  There are several types of white blood cells and each is specialized for certain types of immune response.

White blood cell levels are useful for pointing to many conditions.  They can be high or low for many reasons.  They are commonly used to determine whether or not a patient has an infection.  A “left shift” in the white count indicates presence of high numbers of immature white cells, often called bands.  A left shift can occur for a number of reasons.  It is a natural response to infection as the body tries to make enough white cells to fight the infection.  A “right shift” refers to the absence or low level of bands, new white cells.  This indicates suppression of bone marrow.

Normal range for white blood cell count:

  • 0-11.0 x 109 cells/L

Types of white blood cells can be quantified as either a percentage of total white cells or as an absolute count.  Normal white cell count varies with age, especially neutrophils, lymphocytes and monocytes.

Normal range for neutrophil count:

  • 8-7.7 x 109 cells/L
  • 35-80% of total white cells

Normal range for eosinophil count:

  • 0-0.8 x 109 cells/L
  • 0-4% of total white cells

Normal range for lymphocyte count:

  • 8-4.8 x 109 cells/L
  • 18-44% of total white cells

Normal range for monocyte count:

  • 2-0.9 x 109 cells/L
  • 7-12.5% of total white cells

Normal range for basophil count:

  • 0-0.1 x 109 cells/L
  • 0-1.2% of total white cells

Explain the tests: Complete blood cell count (CBC) – Low white blood cell count (Part six)

Low white blood cell count is called leukopenia. Due to mast cell involvement in many bodily processes, leukopenia can occur for many reasons.

Reasons for leukopenia:

  • Bone marrow suppression
  • Disorder of white cell production or white cell precursors
  • Proliferative disease of other cell types in the bone marrow
  • Mechanical destruction of white blood cells, as in splenomegaly (swollen spleen)

Some conditions that interfere with making enough white blood cells:

  • Certain infections, such as tuberculosis, malaria, dengue fever, Lyme disease and viral infections
  • Sepsis
  • Nutritional deficiency, such as low copper or zinc
  • Nutritional toxicity of certain minerals, such as arsenic

Some proliferative diseases that interfere with making white blood cells:

  • Hodgkin’s lymphoma
  • Myelofibrosis

Conditions that affect white cell precursors:

  • Aplastic anemia
  • Myelodysplastic syndrome
  • Damage to precursors by radiation exposure or chemotherapy

Conditions that cause damage to white cells:

  • Splenomegaly, swollen spleen
  • Lupus

 

Medications that interfere with making enough white blood cells:

  • Immunosuppressants, like mycophenolate, cyclosporine and TNF blockers
  • Interferon preparations, like Betaseron
  • Other medications like clozapine, bupropion, minocycline, lamotrigine and valproic acid
  • Chemotherapy
  • Radiation

Explain the tests: Complete blood count (CBC) – Red cell indices (Part 4)

A number of red blood cell tests are performed together in a complete blood count (CBC).  These tests  (called red cell indices) are assessed together to point to specific causes of red blood cell dysfunction.  These tests include:

Red blood count: The count of all red blood cells in a volume of blood

  • Adult women: 3.9-5.0 million cells/µL
  • Adult men: 4.3-5.7 million cells/µL
  • Please refer to previous posts for detailed discussion of causes of low and high RBC.

Hemoglobin (Hb): The amount of hemoglobin in a volume of blood

  • Adult women: 12.0-15.5 grams/dL
  • Adult men: 12.5-17.5 grams/dL
  • Hemoglobin constitutes about 95% of the mass of a red blood cell.
  • Hemoglobin binds oxygen so that red cells can carry them through the blood into the tissues.
  • Common causes of low hemoglobin include vitamin or mineral deficiency, chronic inflammation, autoimmune disease, hemoglobinopathies, thalassemia, GI bleeding, surgery and blood loss.
  • Common causes of high hemoglobin include lung disease, neoplastic conditions including cancers, and dehydration.
  • If red blood cell count and hematocrit are low, usually hemoglobin is low, too. If red blood cell count and hematocrit are high, usually hemoglobin is high, too.
  • Even if red blood cell count is normal, low hemoglobin will cause symptomatic anemia.
  • Anemia is a decreased ability to carry oxygen from lungs to tissues.

Hematocrit (HCT): The portion of a volume of blood that is red blood cells

  • Adult women: 34.0-44.5%
  • Adult men: 38.8-50.0%
  • Equal to (red blood cell count)/(volume of blood measured)
  • Used to assess severity of blood loss.
  • Common causes of low hemoglobin include vitamin or mineral deficiency, chronic inflammation, autoimmune disease, hemoglobinopathies, thalassemia, GI bleeding, surgery and blood loss.
  • Common causes of high hemoglobin include lung disease, neoplastic conditions including cancers, and dehydration.
  • If red blood cell count and hemoglobin are low, usually hematocrit is low, too. If red blood cell count and hemoglobin are high, usually hematocrit is high, too.

Definitions:

  • Microcytic anemia: low MCV
  • Normocytic anemia: normal MCV
  • Macrocytic anemia: high MCV
  • Hypochromic anemia: low MCH
  • Normochromic anemia: normal MCH
  • Hyperchromic anemia: high MCH

Mean corpuscular volume (MCV): Identifies if red cells are the right size

  • 80-96 fL/cell
  • Equal to (hematocrit)/(red blood cell count)
  • The size of red cells tells you what causes anemia.
  • Low MCV with low red cell count and low hemoglobin indicates microcytic anemia.
  • Common causes of microcytic anemia (low MCV) include iron deficiency, blood loss, anemia of chronic inflammation, sideroblastic anemia, thalassemia, pyridoxine deficiency and lead poisoning.
  • High MCV with low red cell count and low hemoglobin indicates macrocytic anemia.
  • Common causes of macrocytic anemia (high MCV) include megaloblastic anemia, alcoholism, COPD, hypothyroidism, MDS, liver disease and deficiency of vitamin B12 and/or folate.

Mean corpuscular hemoglobin (MCH): The average hemoglobin in a red blood cell in a volume of blood

  • 5-33.2 pg/cell
  • Equal to (hemoglobin)/(red blood cell count)
  • MCH usually mirrors MCV. If MCV is low, MCH is usually low.  If MCV is high, MCH is usually high.
  • Common causes of low MCH include iron deficiency, blood loss, anemia of chronic inflammation, sideroblastic anemia, thalassemia, pyridoxine deficiency and lead poisoning.
  • Common causes of high MCH include megaloblastic anemia, alcoholism, COPD, hypothyroidism, MDS, liver disease and deficiency of vitamin B12 and/or folate.

Mean corpuscular hemoglobin concentration (MCHC): Determines size of red cells

  • 4-35.5 g/dL
  • Equal to (hemoglobin)/(hematocrit)
  • Low MCHC is associated with hypochromic (“too little color”) anemia. Cells with less hemoglobin have less intense red color.  Patients with hypochromic anemia often have a green tinge to their skin.
  • MCHC is usually low in microcytic anemia.
  • MCHC is sometimes normal in some macrocytic anemias. This is called normochromic anemia (“normal color”).
  • Common causes of low MCHC include thalassemia, vitamin B6 deficiency, lead poisoning, Faber’s syndrome, GI bleeding and iron deficiency.
  • Common causes of normal MCHC in the presence of anemia (normocytic anemia) include anemia of chronic inflammation, aplastic anemia, blood loss, hemolysis, and deficiency of vitamins B2 or B6.
  • High MCHC is associated with hyperchromic (“too much color”) anemia.
  • Common causes of high MCHC include sickle cell disease, hereditary spherocytosis, autoimmune hemolytic anemia and hemoglobin C disease.

Red blood cell distribution width (RDW): The amount of variation in the size of red cells

  • 5-14.5%
  • RDW is normal or high. A “low” RDW should be read as normal.
  • RDW helps to identify the cause of anemia.
  • A high RDW indicates that there are large amounts of both new and mature red cells.
  • Variation in size of red cells is called anisocytosis.
  • Common causes of high RDW include

Reticulocyte count: The amount of new red cells in a volume of blood

  • 5-1.5%
  • Elevated reticulocyte count is called reticulocytosis.
  • Common causes of reticulocytosis include hemolytic anemia, pernicious anemia, deficiency of iron, vitamin B12 or folate, anemia of chronic inflammation, cancers affecting bone marrow and chemotherapy.

In conditions with low RBC, low hemoglobin and/or low hematocrit:

  • Low MCV with high RDW: Iron deficiency anemia
  • High MCV with high RDW: Vitamin B12 and/or folate deficiency
  • Variable MCV (low, high or normal) with high RDW: Mixed deficiency (iron and B12 or folate)
  • Normal MCV with high RDW: Large blood loss (hemorrhage)
  • Normal MCV with normal MCH: chronic illness, aplastic anemia, prosthetic heart valves, sepsis or kidney failure
  • Low MCV with low MCH: iron deficiency, thalassemia, lead poisoning, long term inflammation
  • High MCV with normal or high MCH: deficiency of B12 or folate

Explain the tests: Complete blood count (CBC) – High red cell count (Part 3)

A number of conditions can cause high red blood cell count.  This is called polycythemia.  Red cells are responsible for bringing oxygen from the lungs to the tissues. If the blood is getting less oxygen than normal, the bone marrow will produce more red cells to compensate.  Excessive release of erythropoietin, a molecule that triggers red cell production, can also cause high red blood cell count.  Additionally, changes in amount of fluid in the blood stream can artificially alter red blood cell and hemoglobin levels.

Normal range for red blood count:

  • Adult women: 3.9-5.0 million cells/µL
  • Adult men: 4.3-5.7 million cells/µL

Reasons for making too many red blood cells:

  • High levels of erythropoietin, a molecule that tells the bone marrow to make red cells
  • Lower levels of oxygen in blood stream
  • Neoplastic conditions
  • Relative polycythemia, in which reduction of blood volume causes an artificial increase in red blood cells

Some conditions that cause lower oxygenation of the blood, triggering polycythemia:

  • Lung diseases, such as COPD, sleep apnea and pulmonary fibrosis.
  • Heart conditions, such as congestive heart failure.
  • Carbon monoxide poisoning.
  • Hemoglobin defects, such as 2,3-BPG deficiency, which causes hemoglobin to hold onto oxygen too tightly.
  • Lengthy stays at high altitude.

Some conditions that cause elevated erythropoietin:

  • Poor blood flow to the kidney, such as in narrowing of the renal artery, hydronephrosis and kidney cysts. The body interprets as low oxygenation.
  • Chuvash polycythemia, which causes overactivity of the erythropoietin gene.

Some neoplastic conditions that cause excessive proliferation of red cells:

  • Polycythemia vera. This myeloproliferative disorder (MPN) is strongly associated with the JAK2 V617F mutation.
  • Cancers such as renal cell carcinoma and adenocarcinoma.

Situations that cause artificially high red blood cell count:

  • Hypovolemia, from dehydration, alcoholism, obesity, smoking or third spacing.
  • Use of some diuretics.

Some medications that cause secondary polycythemia:

  • Anabolic steroids
  • Testosterone

 

Special notes on high red cell count for mast cell patients:

  • Polycythemia vera is a myeloproliferative neoplasm like systemic mastocytosis. It is a common comorbidity for patients with SM-AHNMD.  Some SM patients are positive for the JAK2 V617F mutation without having polycythemia vera.
  • Third spacing (fluid from the blood stream becoming trapped in the tissues) occurs in many mast cell patients as a regular symptom, as well as during anaphylaxis. This can cause the red cell count to appear artificially high.

Explain the tests: Complete blood count (CBC) with differential and platelets (Part One)

A complete blood count (CBC), also called full blood count (FBC) in some countries, is one of the most frequently ordered diagnostics.  A CBC quantifies and describes the types of cells found in the blood.  These cells include white blood cells (WBC, also called leukocytes), red blood cells (RBC, also called erythrocytes) and platelets (also called thrombocytes).

There are two commonly methods for counting blood cells, automated and manual.

In automated counting, the cells are counted by a machine called a flow cytometer.  Flow cytometers identify cells by shining a laser through a sample of the blood and using the way the light bounces off the cells to determine what kind of cells they are.   This bouncing of light is called scatter.  Flow cytometers measure forward scatter determines the diameter of a cell.  Side scatter determines granularity, how many granules are inside the cell. While this method is generally quite precise, if a cell is not shaped normally, the flow cytometer may count it incorrectly.

In manual counting, the blood is diluted and placed into a special chamber with grid lines called a hemocytometer.  The chamber is viewed under a microscope and the cells are counted by eye.  As someone who has counted lots of cell suspensions by eye, it can be hard to be exact.  This method works for red and white blood cells.

To evaluate abnormality in cell shape, a blood smear is made from the original blood sample.  A smear slide is made by smearing a thin layer of blood onto a glass slide.  Once the blood is dried on the slide, stains are then used to colorize the cells to make them easier to see and distinguish.  Giemsa is a commonly used stain for this purpose (fun fact: mast cells can be visualized with Giemsa stain).  Other stains can also be used. This method allows abnormalities in shape of red and white cells to visualized.

 

A CBC usually includes the following tests:

Total white blood cell count

  • The count of all white blood cells in a volume of blood;
  • Unit is cells/liter

Total red blood cell count

  • The count of all red blood cells in a volume of blood
  • Unit is cells/liter

Hemoglobin (Hb)

  • The amount of hemoglobin in a volume of blood
  • Unit is grams/deciliter

Hematocrit (Hct; also called packed cell volume, PCV)

  • The portion of a volume of blood that is red blood cells
  • Unit is percentage

Mean corpuscular volume (MCV)

  • The volume occupied by red blood cells in a volume of blood
  • Identifies if red cells are the right size
  • Unit is femtoliters/cell

Mean corpuscular hemoglobin (MCH)

  • The average hemoglobin in a red blood cell in a volume of blood; the amount of hemoglobin divided by the red blood cell count; mass of hemoglobin divided by number of red blood cells in a volume of blood; unit is picograms/cell
  • Mean corpuscular hemoglobin concentration (MCHC): the average concentration of hemoglobin in a volume of red blood cells; determines size of red cells; hemoglobin divided by hematocrit; unit is grams/liter

Red blood cell distribution width (RDW)

  • The amount of variation in the size of red cells
  • Can only be high or normal
  • High RDW means red cells show a wide range of size

Reticulocyte count

  • The amount of new red cells in a volume of blood
  • Unit is percentage

 

A CBC with differential and platelets will include the following tests:

Neutrophil count

  • The count of neutrophils in a volume of blood
  • Neutrophils are inflammatory cells that fight infections and initiate inflammatory response
  • Unit is cells/liter

Lymphocyte count

  • The count of lymphocytes in a volume of blood
  • B cells, T cells and NK cells are lymphocytes that detect pathogens in different ways
  • Unit is cells/liter

Monocyte count

  • The count of monocytes in a volume of blood
  • Monocytes respond to inflammatory signals and develop into specialized tissue cells
  • Unit is cells/liter

Eosinophil count

  • The count of eosinophils in a volume of blood
  • Eosinophils fight parasites and participate in allergic response
  • Unit is cells/liter

Basophil count

  • The count of basophils in a volume of blood
  • Basophils fight parasites and participate in allergic response
  • Unit is cells/liter

Platelet count

  • The count of plateletsin a volume of blood
  • Platelets stop bleeding
  • Unit is platelets/liter

Mean platelet volume (MPV)

  • The volume occupied by platelets in a volume of blood
  • Identifies if platelets are the right size
  • Unit is femtoliters/platelet