What are white blood cells? 

White blood cells, also called leukocytes, are cells that your body makes to help fight infections. There are several kinds of white blood cells. The two most common types are lymphocytes and neutrophils. Neutrophils are also sometimes called granulocytes or polymorphonuclear leukocytes (PMNs or "polys"). 

A white blood cell count (WBC) is performed by counting the number of white
blood cells in a sample of your blood. A normal WBC is in the range of 4,000 to
11,000 cells per microliter (mm3).

            W.B.C. (White Blood Cell Count)

Normal Adult Range: 3.8 - 10.8 thous/mcl
Optimal Adult Reading: 7.3
Higher ranges are found in children, newborns and infants.

What are lymphocytes? 

Lymphocytes come from your lymph tissue (spleen, lymph nodes, thymus gland). 
There are different kinds of lymphocytes, including CD4 cells (T-helper cells) and
CD8 cells (T-suppressor cells). Lymphocytes identify foreign substances from
bacteria or viruses in your body and produce antibodies and cells that specifically
target them. It takes from several days to weeks for lymphocytes to recognize and
attack a new foreign substance.

What are neutrophils? 

Neutrophils are a major part of your body’s defense against bacterial infections. 
When the WBC is low, there may not be enough neutrophils to defend you against
bacterial infections. 

Neutrophils are made in the bone marrow and circulate in the bloodstream. 
Neutrophils move out of the blood vessels into the infected tissue to attack the
bacteria. The pus in a boil (abscess) is made up mostly of neutrophils. Normally a
serious bacterial infection causes the body to produce an increased number of
neutrophils, resulting in a higher than normal WBC. 

A normal absolute neutrophil count (ANC) is in the range of 1,500/mm3 to
8,000/mm3. If the ANC is below 500/mm3 for an extended period of time, your risk of serious bacterial infection may increase significantly. A low neutrophil count is also called neutropenia. 

White blood cells main function is to fight infection, defend the body by phagocytosis against invasion by foreign organisms, and to produce, or at least transport and distribute, antibodies in the immune response.

Each cell, or leukocyte, has a different job in the body which is explained in the Differential section.

Differential

NEUTROPHILS and NEUTROPHIL COUNT  

LYMPHOCYTES and LYMPHOCYTE COUNT

MONOCYTES and MONOCYTE COUNT

EOSINOPHILS and EOSINOPHIL COUNT

BASOPHILS and BASOPHIL COUNT

NEUTROPHILS and NEUTROPHIL COUNT      

Also known as Granulocytes or segmented neutrophils, this is the main defender of the body against infection and antigens. High levels may indicate an active infection, a low count may indicate a compromised immune system or depressed bone marrow (low neutrophil production.

Normal Adult Range: 48 - 73 %
Optimal Adult Reading: 60.5
Normal Children’s Range: 30 - 60 %
Optimal Children’s Reading: 45

LYMPHOCYTES and LYMPHOCYTE COUNT

Lymphocytes are involved in protection of the body from viral infections such as measles, rubella, chickenpox, or infectious mononucleosis. Elevated levels may indicate an active viral infection and a depressed level may indicate an exhausted immune system or if the neutrophils are elevated an active infection.

Normal Adult Range: 18 - 48 %
Optimal Adult Reading: 33
Normal Children’s Range: 25 - 50 %
Optimal Children’s Reading: 37.5

MONOCYTES and MONOCYTE COUNT

These cells are helpful in fighting severe infections and are considered the bodies second line of defense against infection and are the largest cells in the blood stream. Elevated levels are seen in tissue breakdown or chronic infections, carcinomas, leukemia (monocytic) or lymphomas. Low levels are indicative of a state of health.

Normal Adult Range: 0 - 9 %
Optimal Adult Reading: 4.5

EOSINOPHILS and EOSINOPHIL COUNT

Eosinophils are used by the body to protect against allergic reactions and parasites. Therefore, elevated levels may indicate an allergic response. A low count is normal.

Normal Adult Range: 0 - 5 %
Optimal Adult Reading: 2.5

BASOPHILS and BASOPHIL COUNT

Basophilic activity is not fully understood but it is known to carry histamine, heparin and serotonin. High levels are found in allergic reactions, low levels are normal.

Normal Adult Range: 0 - 2 %
Optimal Adult Reading: 1

What happens when your white cells are to low on treatment?    

People taking the 1.0 and 1.5mcg/kg dose of peg-interferon experienced slightly more side effects than those on the other two doses. The most common side effects included headaches, fatigue, flu-like symptoms, depression, and decreases in white blood cell counts, platelets (cells needed for blood-clotting) and neutrophils (a type of white blood cell that helps control bacterial and other infections).       

What causes a low neutrophil count? 

Neutrophils die continuously from age or from fighting infections, and your bone
marrow must make new neutrophils to replace them. When something reduces
production of neutrophils in your bone marrow, the neutrophil count will drop and
may become dangerously low. 

Prescription medications, such as trimethoprim-sulfamethoxazole (TMP-SMX,
Bactrim, Septra), ganciclovir, zidovudine (AZT), interferon, pyrimethamine,
primaquine, and many chemotherapy agents used for Kaposis' sarcoma and
lymphoma are common causes of neutropenia. In almost all cases, drug-induced
neutropenia (low white count) resolves after the agent is stopped or its dosage is reduced. 
 

Drugs that Help Low White Count

Neupogen (G-CSF): a colony stimulating factor (CSF)that signals the bone marrow to increase output of white cells (specifically neutrophils), which help to fight bacterial infections.

Neulasta: a protein that stimulates the production on white blood cells.

Neutropenia during combination therapy of Interferon and Ribavirin

Alejandro Soza, James E. Everhart, Marc G. Ghany, Edward Doo, Theo Heller, Kittichai Promrat, Yoon Park,

T. Jake Liang, and Jay H. Hoofnagle

Interferon therapy of hepatitis C causes a decrease in neutrophil counts, and neutropenia is a common reason for dose adjustment or early discontinuation. However, it is unclear whether neutropenia caused by interferon is associated with an increased rate of infection. In this study, we assessed factors associated and clinical consequences of neutropenia before and during interferon therapy of chronic hepatitis C. A total of 119 patients with chronic hepatitis C treated with the combination of interferon alfa and ribavirin were analyzed. In these studies, neutropenia was not used as an exclusion or dose modification criterion. In multivariate analysis, only black race was associated with baseline neutropenia. During treatment, neutrophil counts decreased by an average of 34%. Among 3 blacks with baseline neutropenia without cirrhosis or splenomegaly, there was little or no decrease in neutrophil counts (despite typical decreases in platelet and lymphocyte counts). Documented or suspected bacterial infections developed in 22 patients (18%), but in no patient with neutropenia. United States population estimates suggest that 76,000 blacks with hepatitis C have neutrophil counts below 1,500 cells/

L and might be denied therapy if this exclusion criterion was generally applied. In conclusion, neutropenia is frequent during treatment of hepatitis C with interferon and ribavirin, but it is not usually associated with infection.

Constitutional neutropenia, which is common among blacks, should not exclude patients

from therapy with interferon as these patients usually have minimal further decreases in neutrophil counts on therapy and are not excessively prone to bacterial infections.

HEPATOLOGY

2002;36:1273-1279.)

 Neutrophil counts can fall to levels that are

associated with an increase in risk of bacterial infections

and sepsis. Indeed, in the recent large randomized con-

trolled trials of pegylated or standard interferon combined

with ribavirin neutropenia was listed as the most common

reason for dose reduction (18% of patients) and was a

reason for early drug discontinuation in 1% of patients.

Furthermore, most studies have excluded patients with

preexisting neutropenia ( 1,500 cells/

L). This exclusion criterion has major implications for select population

groups with hepatitis C. Neutropenia is more common

among black patients than whites and a larger proportion

of blacks are excluded from trials of therapy of hepatitis C

for this reason. Whereas the consequences of neutropenia

are believed to be substantial, there is little evidence for

adverse clinical implications of neutropenia induced by

interferon particularly in patients with preexisting low

white cell counts. At the Clinical Center of the National

Institute of Health, clinical studies of therapy of hepatitis

C have not used neutropenia as an exclusion criterion. We

retrospectively have analyzed neutrophil counts during

therapy of hepatitis C and occurrence of bacterial infec-

tions. The effect of using neutropenia to exclude potential

patients from treatment was determined among white

and black participants in the Third National Health and

Nutrition Examination Survey (NHANES 3).

 Below is an excerpt from the study found at the url listed below:

 In this analysis of neutrophil counts among 119 pa-

tients treated at a single referral center, neutropenia was

not used as an exclusion criterion and therapy was safely

accomplished despite decreases in neutrophils below the

usual levels that lead to dose reduction or drug interrup-

tion. Bacterial infections did not occur in neutropenic

patients, and the only severe infection that was identified

occurred in an elderly patient with preexisting cirrhosis.

Of potential interest, the only baseline measure that pre-

dicted subsequent infection was low reticulocyte count.

We are unaware of other information linking reticulocyte

count to subsequent infections. Nevertheless, the associ-

ation was strong and deserves further investigation.

There was poor correlation between total white blood

cell count and neutrophil count in patients with neutro-

penia, indicating that measurement of absolute neutro-

phil count instead of total white blood cell count is

necessary in monitoring therapy. Of greatest importance,

3 patients were treated who appeared to have constitu-

tional neutropenia, marked by persistently low neutrophil

counts (below 1,500 cells/

 Click below to read the study in its entirety;

 PDF]Neutropenia During Combination Therapy of Interferon Alfa and ...
File Format: PDF/Adobe Acrobat - View as HTML
... information linking reticulocyte count to subsequent infections. ... marked by persistently
low neutrophil counts ... typical increases in neutrophils during bacterial ...

hepcvets.com/info/2002/nov/hepcinfo1273.pdf -  

Laboratory Tests: The following laboratory tests are recommended prior to initiating interferon beta-1b therapy and at periodic intervals thereafter:

http://216.239.57.100/search?q=cache:VXKGFNBseqcC:www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%2520Monographs/CPS-%2520(General%2520Monographs-%2520B)/BETASERON.html+value+total+white+count+discontinue+interferon+therapy&hl=en&ie=UTF-8

Thyroid function test, hemoglobin, complete and differential white blood cell counts, platelet counts and blood chemistries including liver function tests. A pregnancy test, chest roentgenogram and ECG should also be performed prior to initiating interferon beta-1b therapy. Also an eye exam should be preformed.

The study protocol stipulated that interferon beta-1b therapy be discontinued in the event the absolute neutrophil count fell below 750/mm When the absolute neutrophil count had returned to a value greater than 750/mm therapy could be restarted at a 50% reduced dose. No patients were withdrawn or dose-reduced for neutropenia or lymphopenia.

Similarly, if AST/ALT levels exceeded 10 times the upper limit of normal, or if the serum bilirubin exceeded 5 times the upper limit of normal, therapy was discontinued. In each instance during the controlled MS trial, hepatic enzyme abnormalities returned to normal following discontinuation of therapy. When measurements had decreased to below these levels, therapy could be restarted at a 50% dose reduction, if clinically appropriate. Dose was reduced in two patients due to increased liver enzymes; one continued on treatment and one was ultimately withdrawn.

White blood counts: What is to low ?

Combination therapy with interferon and ribavirin commonly drives down the white count and especially a certain type of white cell called neutrophils that are important in fighting bacterial infections. It is important for people to appreciate that it is the interferon part of the treatment that really drives down the white count. It is possible that the Rebetol (ribavirin) part contributes but we know that when we use interferon alone, we see the same problem. As a result, if the white count or the neutrophil count gets to be very low, we typically adjust down the interferon dose and not the Rebetol dose.

There are a couple of additional comments. First, with time and experience, we have to come to appreciate that our hepatitis C patients can tolerate a lower white count on treatment than we originally felt comfortable with. If we are able to keep the neutrophil count (ANC) above 750, patients do not typically develop infections. Secondly, we can sometimes use a second drug called GM-CSF or Neupogen to keep up the white count. Neupogen is a drug that is used primarily for cancer patients receiving chemotherapy. It is effective in getting the bone marrow to make more white cells. Like interferon, it has to be injected.

http://www.medhelp.org/forums/hepatitis/archive/904.html

Neutrophil% x White Blood Cell = Absolute Neutrophil Count

For example, if a person's white blood cell count were 6,000 cells, and neutrophils made up 50% of those, that person's absolute neutrophil count would be 3,000.

A normal range for neutrophil% is between 33% and 72%. This makes the normal range for the ANC between 1500 and 7200. Since every individual is unique, you should consult your physician or nurse if you have questions concerning your white blood cell count and ANC.

 If you’re total white count is 1.0 (1000) or below then your neutrophils would be around 500… to low to continue therapy. Although treatment is not always discontinued (in some cases) the dose is cut back until the white count increases. 

What are Red Blood Cells ?

Red blood cells carry oxygen from the lungs to cells throughout the body. This is measured by three main tests. The Red Blood Cell Count (RBC) is the total number of red blood cells. Hemoglobin (HGB) is a protein in red blood cells that actually carries oxygen from the lungs to the rest of the body. Hematocrit (HCT) measures the percentage of blood volume taken up by red blood cells.

A high RBC is common for people who live at high altitude. It's a way the body adjusts to thinner oxygen.

Very low readings for RBC, hemoglobin and hematocrit can indicate anemia. With anemia, the cells do not get enough oxygen to function normally. People with anemia feel tired all the time and might look pale.

            R.B.C. (Red Blood Cell Count)

Normal Adult Female Range: 3.9 - 5.2 mill/mcl
Optimal Adult Female Reading: 4.55
Normal Adult Male Range: 4.2 - 5.6 mill/mcl
Optimal Adult Male Reading: 4.9
Lower ranges are found in Children, newborns and infants

HEMOGLOBIN (HGB)

Hemoglobin is the main transport of oxygen and carbon dioxide in the blood. It is composed of globin a group of amino acids that form a protein and heme which contains iron atoms and the red pigment, porphyrin. As with Hematocrit, it is an important determinant of anemia (decreased), dehydration (increased), polycythemia (increased), poor diet/nutrition, or possibly a malabsorption problem.

Normal Adult Female Range: 12 - 16%
Optimal Adult Female Reading: 14
Normal Adult Male Range: 14 - 18%
Optimal Adult Male Reading: 16
Normal Newborn Range: 14 - 20%
Optimal Newborn Reading: 17

HEMATOCRIT (HCT)

The word hematocrit means "to separate blood," a procedure which is followed following the blood draw through the proper use of a centrifuge. Hematocrit is the measurement of the percentage of red blood cells in whole blood. It is an important determinant of anemia (decreased) , polycythemia (increased), dehydration (elevated), increased R.B.C. breakdown in the spleen (elevated), or possible overhydration (elevated)

Normal Adult Female Range: 37 - 47%
Optimal Adult Female Reading: 42%
Normal Adult Male Range 40 - 54%
Optimal Adult Male Reading: 47
Normal Newborn Range: 50 - 62%
Optimal Newborn Reading: 56

What are platelets? 

Platelets are cell fragments from the bone marrow that circulate through the
bloodstream, helping your blood to clot. In places where there are breaks in vessels,
platelets form plugs with serum proteins (clotting factors) to prevent blood loss while
healing takes place. 

What is a platelet count? 

A platelet count is a blood test done by counting the number of platelets in a known
volume of blood. A normal platelet count is in the range of 150,000 to 450,000 per
microliter (mm3). A low platelet count is called thrombocytopenia. If your platelet
count drops below 50,000/mm3, you may not be able to stop bleeding after a serious
injury. If you have a platelet count below 20,000/mm3, bleeding may occur
spontaneously. 

What are the symptoms and signs of a low platelet count? 

Persons with a low platelet count may bruise easily or bleed from the mouth or
rectum. If any of these symptoms are present, your platelet count could be low, but
other explanations are also possible.

            PLATELET COUNT

Platelets (also known as thrombocytes) are the smallest formed elements of the blood. They are vital to coagulation of the blood to prevent excessive bleeding. Elevated levels suggest dehydration or stimulation of the bone marrow where the cells are produced and decreased levels may indicate an immune system failure, drug reactions, B12 or folic acid deficiency.

Normal Adult Range: 130 - 400 thous/mcl
Optimal Adult Reading: 265
Higher ranges are found in children, newborns and infants.

          Hematology  

MCH (Mean Corpuscular Hemoglobin)

Hemoglobin x 10
R.B.C.

Mean Corpuscular Hemoglobin (MCH) gives the average weight of hemoglobin in the red blood cell. Due to its use of red blood cells in its calculation, MCH is not as accurate as MCHC in its diagnosis of severe anemia's. Decreased MCH is associated with microcytic anemia and increased MCH is associated with macrocytic anemia.

Normal Adult Range: 27 - 33 pg
Optimal Adult Reading: 30

MCV (Mean Corpuscular Volume)

Hematocrit x 10
R.B.C.

The Mean Corpuscular Volume reflects the size of red blood cells by expressing the volume occupied by a single red blood cell. Increased readings may indicate macrocytic anemia or B6 or Folic Acid deficiency and decreased readings may indicate microcytic anemia, possibly caused by iron deficiency.

Normal Adult Range: 80 - 100 fl
Optimal Adult Reading: 90
Higher ranges are found in newborns and infants

MCHC (Mean Corpuscular Hemoglobin Concentration)

Hemoglobin x 100
Hematocrit

This test measures the average concentration of hemoglobin in red blood cells. It is most valuable in evaluating therapy for anemia because Hemoglobin and Hematocrit are used, not R.B.C. in the calculation. Low MCHC means that a unit of packed R.B.C.’s contain less hemoglobin than normal and a high MCHC means that there is more hemoglobin in a unit of R.B.C.’s. Increased MCHC is seen in spherocytosis, and not seen in pernicious anemia whereas decreased levels may indicate iron deficiency, blood loss, B6 deficiency of thalassemia.

Normal Adult Range: 32 - 36 %
Optimal Adult Reading: 34
Higher ranges are found in newborns and infants

What happens when Ribavirin or (COPEGUS) lowers your red blood count?

Low platelets are referred to as thrombocytopenia. Low red blood cells or hemoglobin is called anemia.

Will Procrit help low platelets? No, it won't , there are other medications which can increase platelets. But if you're  anemic, definitely talk to your doctor about Procrit.

Drugs to Help low platelets:

Neumega: a growth factor that stimulates the bone marrow to increase production of platelets.

In the mid-1990s, a new drug was added to the arsenal. This is ribavirin (Rebetron®). Ribavirin is an antiviral drug which has been used in children to treat a serious lung virus. It was approved by the FDA in 1998 for use in patients with Hepatitis C. Ribavirin does not work when used alone - it requires combination therapy with interferon to see a response. The most important use of ribavirin is it's apparent ability to keep patients who respond to the interferon in a sustained response (40-50%!). Not everyone can take ribavirin, however. The drug causes a fairly severe anemia (low red blood cells), which can complicate high blood pressure, diabetes, or heart disease.

Ribavirin accumulates in the red blood cells and damages them, shortening their life in the body. The body compensates by making more red blood cells, but many people cannot keep pace with the accelerated loss of red cells caused by ribavirin. Red blood cells carry oxygen from the lungs to the rest of the body, and if the red blood cell count drops too much, a person will feel easily tired. Most people have only a small reduction in red blood cells, but for some people the drop is severe. For some people, even a minor drop in red blood cells can be dangerous. For example, someone with heart disease might develop a heart attack if the red cell count were to drop, or someone who is already anemic from another cause could become severely anemic on ribavirin. Therefore it is important to monitor the red blood cell count while on ribavirin, and to be doubly careful with persons with heart disease or pre-exisiting anemia.
The anemia caused by ribavirin resolves when ribavirin is stopped, usually within one to two months.

COPEGUS tablets may cause birth defects and/or death of an unborn child.  If you are pregnant, you or your male partner must not take PEGASYS in combination with COPEGUS.  You must not become pregnant while either you or your partner is being treated with the combination of PEGASYS and COPEGUS or for 6 months after stopping therapy.  Men and women should use birth control while taking the COPEGUS with PEGASYS and for 6 months afterwards.  If you or your partner is being treated and you become pregnant either during treatment or within 6 months of stopping treatment, call your doctor right away.

http://www.gidoctors.com/Hepatitis/ribavirin.htm

Red Blood Cells : What is to low?

Adjust the dose of Ribavirin downward (by 200 mg at a time) if significant anemia occurs (hemoglobin less than 10 gm/dL or hematocrit < 30 percent)

Stop Ribavirin if severe anemia occurs (hemoglobin < 8.5 gm/dL or hematocrit < 26 percent).

Hemoglobin:

Normal Adult Female Range: 12 - 16%
Optimal Adult Female Reading: 14
Normal Adult Male Range: 14 - 18%
Optimal Adult Male Reading: 16
Normal Newborn Range: 14 - 20%
Optimal Newborn Reading: 17

Hematocrit:

Normal Adult Female Range: 37 - 47%
Optimal Adult Female Reading: 42%
Normal Adult Male Range 40 - 54%
Optimal Adult Male Reading: 47
Normal Newborn Range: 50 - 62%
Optimal Newborn Reading: 56

http://mobile.handheldmed.com/mobile/niddk/hepc/k.html

Ribavirin Induced Anemia
 07/17/2001

Approximately 10% of patients receiving ribavirin develop significant anemia (1). This anemia results mostly from intravascular hemolysis (premature break up of red blood cells within the blood vessels). The anemia is dose dependent and is not worsened by the presence of interferon therapy. It also resolves within a few weeks after discontinuation of the medicine. On the average, the hemoglobin concentration drops by 2 to 3 g/dl for patients on standard dose ribavirin (1000 mg to 1200 mg a day).

As the hemoglobin falls, patients may experience worsened fatigue, dyspnea on exertion (shortness of breath with exertion), lightheadedness, palpitations and even chest pain especially if there is preexisting coronary artery disease and if the hemoglobin concentration falls below 10g/dl.

Managing Hemoglobin Levels

Because hemoglobin levels are routinely monitored during the course of therapy, it is quite easy to identify the emergence of the drug-induced anemia before significant symptoms occur. When the hemoglobin concentration falls below 10g/dl, ribavirin dosage should be decreased to around 600mg/day. This decrease in dose often results in a 1 g/dl to 1.5 g/dl increase in the hemoglobin. While dose reduction has been the standard of care in this setting, recent data suggest that the concomitant use of erythropoietin (a hormone that stimulates the bone marrow to make more red blood cells) may be beneficial in the management of ribavirin induced anemia (2).

In summary, ribavirin induced decrease in hemoglobin levels is common; significant anemia may result and require dose reduction. It is rare for the drug to be stopped as a result of anemia. There is data that erythropoietin may help in the management of the anemia, but erythropoietin is expensive and the data preliminary. This author would like to see more data on this issue before advocating its routine use for patients.

References:

1. McHutchinson JG, Gordon SC, Schiff ER et al. (1998). Interferon alpha-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. NEJM; 339:1485-1492

2. Wasserman R, Braun N, Hassanein TI et al. Once weekly epoetin alpha increases hemoglobin and decreases ribavarin discontinuation among HCV patients who develop anemia on RBV/INF therapy. Hepatology. 2000; 32: abstract 833.