Content last updated on 11/11/02 with quite a bit of new information
"What Is Neutropenia?"
Cyndi Cramer, BA,RN,OCN
Critical Care, Oncology, & Pediatric Educator
One Contact Hour Self Learning Module
1. Define Neutropenia.
2. Calculate an ANC and explain its
3. Outline causes and risk factors for
4. Identify clinical consequences of
5. Describe management strategies for
What Is Neutropenia?
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When a patient’s immune system becomes compromised
and is at increased risk for infection we look at more then the WBC’s (white
blood cells). We actually look at the differential on the CBC and calculate
the ANC (absolute neutrophil count). By doing this we are able to look
at the precursors of the WBC’s. These are the "baby WBC’s" or immature
blood cells. These are found in the patient’s bone marrow. This number
will give us a more accurate measurement of a patient’s risk for infection.
To measure this we look at the neutrophils (sometimes
also called segs or polys) and the bands. The following formula is used:
Example: Neutrophils = 50 %
Bands = 8%
% neutrophils (also called polys or segs) + % bands
Convert to decimal by dividing by 100 (ex: 48% = 48/100
If you know that 35% = .35 and 3% = .03 then you can
skip this step and just convert your percentage to a decimal
Multiply by WBC = ANC
WBC = 4000
50 + 8 = 58% = 0.58 X 4000 = 2320 = ANC
(note: some lab CBCs will give you the WBC as 4 instead of 4000. You
wouldn't see such a small number for the complete WBC--change it to 4000.
Talk to your lab so you can understand how they are printing out the CBC
with differential if it isn't making sense to you.)
Neutrophils are the body’s first line of defense
and work by:
They normally increase when there is an infection
as part of the patient’s "immune defense system".
Going to the site of infections, damage, or inflammation
to join "the battle"
Causing phagocytosis of particles such as bacteria
Bands are immature neutrophils.
So What Does This Mean?
According to the World Health Organization (WHO)—an
ANC < 2000 = Neutropenia. Some sources push it a little further and
don’t consider the patient to actually be neurtropenic until their ANC
is < 1500.
This becomes significant for patients receiving treatments
that cause these numbers to decrease even further (such as chemotherapy
or radiation therapy). It is also significant in warning us that a patient
is immunosuppressed and at risk for infection and unable to adequately
call on their "immune defense system".
Generally, we follow these guidelines:
Neutropenia = ANC < 2000 (slight risk of infection)
Mild Neutropenia = ANC > 1000 & < 1500 (minimal
risk of infection)
Moderate Neutropenia = ANC > 500 & < 1000
(moderate risk of infection)
Severe Neutropenia = ANC < 500 (severe risk of
Chemotherapy is usually not given to a patient
with an ANC < 1000 (but other circumstances may change this parameter)
So What Causes This?
Treatments such as chemotherapy and radiation therapy.
Neutrophils (and their precursors called stem cells) are constantly being
produced and have a short life span. This makes them very sensitive to
these treatments. For most chemotherapy agents, patient’s blood counts
reach their lowest point (called the nadir) 8 – 10 days after the chemo
(some people say 7-14 days). But this can vary with some drugs causing
a later nadir (as long as 63 days) and more prolonged neutropenia. Recovery
can range from 8 to 89 days.
Radiation induced neutropenia is related to the amount
of exposure and if the site is an area carrying bone marrow (such as the
sternum or skull).
Disease processes that effect the immune system like
cancers, HIV infection, or autoimmune disorders.
Neutropenia is prolonged or the risk is increased with
advanced age, malnutrition, multiple treatments or prolonged treatments,
or with concurrent medications (like antibiotics or steroids).
Neutropenia can be predicted in certain chemotherapy
agents and protocols and patients age 70 and older.
Each time a patient receives a cycle of chemotherapy
or a round of radiation...their risk of neutropenia increases
Go to the Neutropenia Support Association's webpage to get more information
about neutropenia and learn about some non-cancer causes of neutropenia:
This is a registered charity that was formed in 1989 that provides assistance
to neutropenic patients and their families and raises money for education
Patients who have been neutropenic in a previous cycle
of chemo or radiation are at high risk for neutropenia in all subsequent
So What Do We Look For?
If a patient is severely neutropenic—they may not
show the "typical" signs of infection that we are used to looking for.
This is because the body is not producing WBC’s. Normally, when we have
an infection—the WBC’s increase and this is what causes the redness, pus,
and swelling that we are all so familiar with.
The most reliable sign (and many times the only
sign) will be a fever > 100.5 F (38 C). Find out what temperature your
MDs consider to be "a fever". They do not all agree on what the "magic
number" is. You don't want your patient to call them at 2 am and get yelled
at for calling when they don't really have a fever. Then they might not
call when the temperature is actually within this physician's parameter
And remember, if a patient experiences chills or
rigors...this will make the temperature go up. Their temperature should
be taken again!
Of course, if we do see any traditional signs or
symptoms of infection in a patient at risk—we need to take them very
seriously. We need to "round up the usual suspects":
Respiratory: Cough, SOB, crackles, rhonchi, wheezes
GU: Burning, frequency, dysuria, hematuria, cloudy
urine, vaginal discharge
GI: Diarrhea, guiac positive stools
Skin & Mucous Membranes: Redness, tenderness,
swelling, "fungal" white patches
Indwelling devices: IV lines and urinary catheters
symptomatic for infection
Some folks will "act septic" and never even have
positive blood cultures. We still treat them aggressively when they are
Some folks will continue to have fevers without any
signs of infection and while their ANC is increasing to acceptable levels.
In that case, we usually gradually remove the antibiotics and continue
to closely assess the patient. (They may be having "drug fevers" or "tumor
fevers"...but we need to err on the side of caution...)
Note: Studies have shown that patients with
NHL (Non-Hodgkin's Leukemia) have an increased risk of neutropenic complications
Their serum LDH is > 460
Their disease includes bone marrow involvement
Their serum albumin is < 3.5 (highest predicter
of the three)
This risk is greatly increased if they have more
then one of these things
"Prevention is Worth a Pound
Take meticulous care of all IVs and avoid indwelling
urinary catheters if possible. At the first sign of infection get STAT:
blood cultures, urine cultures, chest x-ray, etc…
Good central line care includes aggressive flushing
after meds, fluids, blood products or blood draws. Never use less than
a 10 ml syringe and use at least 10 ml of NS (unless contraindicated as
in neonates). Use 20 ml after blood has been in the line. Use a "jerky"
flush technique to try to wash out the catheter while flushing. Use the
minimum amount of "add-ons" to your IV tubings and minimize catheter manipulation.
Then start ordered antibiotics STAT!
First, get blood cultures from 2 sites and any other
suspicious sites (wounds, urine, stool)
If everything is negative and infection is still suspected---viral
and fungal cultures may be obtained
This is the one time when an antibiotic order is truly
a STAT order...I consider this an Oncology Emergency. If your patient is
septic and has a low ANC--they could die within hours! You need to develop
a "Team" attitude on this. Pharmacy, Nursing, transport personnel, unit
coordinators, and MDs all need to work together on this!
Yes, we are being more "stingy" these days with broad
spectrum antibiotic use (due to antibiotic abuse and the wave of antibiotic
resistant infections plaguing us)...but these patients are an exception
to this. They don't have the time to wait around for "proof" of infection!
And non-oncology nurses need to be educated on this
topic. These patients don't need to be sitting around in a dirty Emergency
Room for hours!
The NCCN guidelines recommend starting antibiotics if
the patient has a Neutropenic Fever (100.5 or greater) with an ANC of 500
or less or if their ANC is 1000 and is likely to go under 500 in the next
48 hours (have they hit their Nadir yet?) or, obviously, if there are any
signs of infection
Other NCCN "high risk" patients include:
patients already in the hospital when becoming febrile
patients needing to be hospitalized for other reasons
cancer not controlled or getting worse
previous stem cell transplant
abnormal liver and kidney function
If antibiotics are not started--the medical team needs
to watch this patient closely and reevaluate at 12-24 hours (and teach
the patient to take their temperature and report elevations or any other
signs of infection)
Teach patients basic
Avoid enemas, rectal temperatures, and anything "invasive"
Frequent and good handwashing (both the patient and
those coming in contact with them)
This is the most important preventive measure!
The CDC has recently come out with new handwashing guidelines
for healthcare workers. They are promoting the use of hand cleaning agents
(That stuff that used to be full of alcohol that you used to clean your
hands all of those times you "should" wash your hands but don't have time
or access to soap and water is fading. There are new products out there
that are gentler on your hands.) You still need to wash "soiled" hands.
But if you washed your hands as much as is recommended--they would become
dry, cracked and raw which is a portal for infection! This is a gentler
way to clean the hands. And, hopefully, will encourage folks to do it more
See the new CDC guidelines at: www.cdc.gov/handhygiene/
Good peri care with voiding or stooling & women
need to wipe front to back after urination
Frequent gentle mouth care with a soft toothbrush.
If your patient has mucositis, too, do not use commercial
mouthwashes. These contain alcohol and dry out the mouth even more. Swish
the mouth out with prescription mouthwashes, or salt water, or baking soda
Use a water soluble lubricant during intercourse and
no intercourse if severely neutropenic (each MD has their own ideas when
their patients can and cannot have sex....and they may even have parameters
advising at what ANC they can do different kinds of sexual activities.
They need to set their guidelines and you need to know what these are.
This is an important topic that we frequently avoid discussing!)
Avoid construction area.
These release fungus into the air (like aspirgillus)
that can be deadly to an immunocompromised patient
Avoiding uncooked food or food that cannot be washed
Avoid contact with people exposed to infectious diseases
(like chicken pox, shingles, flu, colds) and caution with children in day
care or school environments. This includes you! If you have a cough or
runny nose—don’t take care of this patient. And a mask does not help—it
just concentrates your germs in one spot on the mask!
Avoid people recently vaccinated with live vaccines
for 30 days
Flu shots are not recommended. Not because they will
hurt the patient--but because they won't be effective with the immune system
Good "pulmonary toilet" (coughing and deep breathing--ambulation)
Institute "neutropenic precautions". This is just a
reminder to do good handwashing and keep people away that could increase
the patient’s risk of infection. If they have to go somewhere (like radiology)
then they can wear a mask to give them some protection from
all the bugs floating around the medical world. If they are neutropenic
at home—they need to avoid crowds and don’t eat off the salad bar! (Just
imagine all those people hanging over the salad bar, sneezing as they go,
little fingers rubbing runny little noses and then sticking their hands
into the cherry tomatoes…)
You no longer need to place them in "reverse isolation"
and cover yourself or their visitors with masks, gowns, gloves...
To download the NCCN (National Comprehensive Cancer
Network) treatment guidelines for fever and neutropenia in patients with
cancer, go to:
Avoiding fresh fruits, vegetables, flowers, & live
plants (anything grown in dirt has bacteria on it).
Don’t clean kitty litters, or fish tanks, and don’t
New research is being done on Neutropenic Precautions
and we are seeing changes on how we look at these traditional ideas. They
may not need these strict food restrictions. They may be able to garden
if they wear gloves that are clean inside. This has been are very poorly
researched area and we have been doing most of what we do because "that's
way we do it". We are just starting to do some good research in this area
so we will be seeing some new information and probably some changes in
the way we do things in the future...
(this is in a "layman friendly" format)
Go to the NCCN website and
medical professionals can register (free) and view all of the NCCN Guidelines
online or order a free CD with the 2001 guidelines: www.nccn.org
Education is Always a Good Thing!
Teach the patient and family to notify the nurse
or physician at the first sign of any kind of infection (and be sure to
teach them what those signs and symptoms are!)
Stress the importance of calling their doctor if
they have a fever > 100.5 (or whatever parameter their physician considers
reportable)—even if it’s the middle of the night! A severely neutropenic
patient can become septic in a heartbeat. Not wanting to "bother" their
doctor until the morning could have very serious consequences!
Is There Anything That Can Help?
Actually, we have made some significant strides in
recent years in reducing the severity and length of neutropenia in patients
at risk. Remember when we talked about how the neutrophils are the "precursors"
to the WBC’s? Well, several years ago, some people invented something called
a "Hematopoietic Growth Factors" (HGF) or "Colony Simulating Factors" (CSF)
that stimulate these "baby WBC’s" to grow. This is a whole new area of
treatments known as Biological Response Modifiers (BRM’s) or Biotherapy.
The first of these were G-CSF (also known as filgrastim or Neupogen) from
AMGEN and GM-CSF (also known as sargramostim or Leukine or Prokine) now
from Berlex. There are some different FDA approvals for these two drugs.
Contact your drug reps for more information. They are also the best people
to talk with if you have any questions or problems about insurance reimbursement.
(Click to get info about G-CSF, ie Neupogen, from the manufacturers. Read
the whole info page and the clickables to get some great info about fighting
Patients with cancer receiving myelosuppressive chemotherapy
Patients with AML (Acute Myelogenous Leukemia) receiving
induction or consolidation chemotherapy
Patients with cancer receiving bone marrow transplant
patients undergoing peripheral blood stem cell (PBSCT)
collection and therapy
Patients with severe chronic neutropenia
Stating dose is 5 mg/kg SC or IV daily
Use prefilled syringe of 300 mcg if < 132
pounds (not approved in pediatrics--talk with a specialist for off label
Use prefilled syringe of 480 mcg if > 132 pounds and
Increase by 5 mcg/kg in next cycle if desired ANC was
Begin 24 hours after end of chemotherapy
Continue past Nadir (up to 14 days) until ANC >10,000
This is NOT a Sliding Scale based on the Nadir. Do Not
Stop this drug until you've gone past the Nadir! (Don't get routine ANCs
right after chemo--it will go up and you don't want someone to think they
need to stop the growth factor because of this. Your concern for their
ANC should be when they are getting closer to their Nadir or if they are
having signs of infection)
Do not double up before and after the weekend or just
"take the weekend off". You need to give this drug DAILY until the patient
gets through their Nadir!!
Continue in all subsequent cycles
Each time the patient goes through chemotherapy--they
will be "wammied" even more. If they needed support this time--they will
continue to need support!
Leukine info at: www.leukine.com
(Click to get info about GM-CSF, ie Leukine, form the manufacturers. This
has less approvals then Neupogen but is being used in research in other
areas of oncology treatment that are very interesting)
AML following induction chemotherapy in older
adults (> 55 years)
mobilization & after PBSCT
Myeloid reconstitution after autologous BMT
(when you receive your own marrow)
Myeloid reconstitution after allogeneic BMT
(when you receive someone else's marrow)
BMT failure or engraftment delay (failure
or slow to accept the new marrow)
Dose is 250 mcg/m2 per day SC or IV (see prescribing
info at website for more detailed dosing)
Begin after chemotherapy and dose through
We also have a new product: peg-filgrastim
or Neulasta. This is from the people that make Neupogen. This is only given
once (by SC injection) per chemotherapy cycle instead of daily. It's a
"smart" drug. It looks at the patient's neutropenia profile and keeps working
until they start improving. It was made with a bigger molecule that causes
it to accomplish this slow release action.
Go to www.neulasta.com
for more information from the manufacturer.
Nonmyeloid malignancies (like AML, CML) receiving
myelosuppressive anticancer drugs associated with a clinically significant
incidence of febrile neutropenia
Give 6 mg SC (prefilled syringe) one time
Start 24 hrs after the completion of chemotherapy
and don't give closer then 14 days before the next cycle of chemotherapy
The major side affect associated with all
of these drugs is bone pain. This is due to the pressure of the increasing
new cells in the bone marrow pushing on the inside of the bones. This is
actually "good news" and, in most cases, can be easily controlled by Tylenol
or Advil. Occasionally, some people need something stronger.
See the full prescribing information from
each of these companies for a more detailed side effect profile and more
detailed drug information
Talk with each company's drug rep for insurance
reimbursment issues or plans to assist uninsured and underinsured individuals.
They are experts on these topics!
But the most important things that we can do
Identify those patients at risk for neutropenia and
monitor their ANC.
Once these patients are identified—then do everything
that we can to prevent or detect an infection.
Report and start treatment for any suspected infection
STAT (and teach the patient and families to do the same thing.)
What Are Out Patient's Treatment Goals?
Make sure that these growth factors are correctly prescribed
Determine what your patient's actual goals are with
These all require different thought processes on the
part of the patient, family, and you!
Are they going for "the gold"--a cure from cancer?
Are they working on trying to control their cancer?
Or is control not even possible?
Are they just trying to live as long as possible with
If there is a chance of cure (and that is totally up
to the patient when it all comes out in the wash) we need to be aggressive.
People will put up with a lot if they feel they can get a cure. Quality
of life is always an important issue--but most people will make compromises
when their life is at stake.
The MD, NP and bedside nurse can only share the information
they have with the patient. Some cancers have outstanding prognosis and
we would be failing our patients if we didn't do everything we could to
encourage them to take our advice on what treatments have been causing
these great outcomes.
But other cancers have very poor prognosis. But, for
some folks, even very small odds of cure are enough for them to say "do
everything". In those cases, even though the outcome is not encouraging,
our focus is cure. But we need to be sure they are making this decision
with their "eyes wide open".
In either case, people will put up with a great deal
if they are trying to be cured!
The best chance for cure comes with following the recommended
treatments and "staying the course". That doesn't mean taking a break for
a vacation...stopping for severe nausea and vomiting...stopping because
the patient has become Neutropenic...
It is our job to try to control these problems as much
Cancer is a very smart disease. It becomes resistant
to our treatments very quickly. We need to hit it hard, hit it fast, and
hang in there to have the best chance of cure
To learn how to determine Dose Intensity, which will
tell you what percentage of their chemo your patient is getting, contact
your growth factor drug reps. (They can give you literature and/or inservices
on how to do this)
If you are working in a practice setting where you can
impact the scheduling of patients for their chemotherapy, you need to know
how to mathematically figure out how much of their medication they have
received over time. This includes looking at any dose reductions along
with dose delays. It is critical for cancer cure to keep them "on schedule".
You need to try to help manage any side effects or complications of their
chemotherapy and you need to be a "cheerleader" to help them get through
Research is still being conducted to find out what the
optimal Dose Intensity is for each cancer and cancer treatment. We have
good studies showing that Breast Cancer patients have a significant increase
in survival if they get at least 85% of their chemotherapy (see Bonadonna
in bibliography below). There is also good research showing NHL (Non-Hodgkins
Leukemia) patients have a significant increase in survival if they get
at least 75% of their dose of chemotherapy (see Kwak in bibliography below).
We need more research for us to continue to learn about this...
If we are looking at control, people will still put
up with a lot to maintain this, but quality of life becomes a bigger focus.
There are many variables involved (Are we only able to realistically control
this disease for a very short time...or can we expect years of control...or
maybe can we control this indefinately---this is coming...)
So, understand what your patient's goals are. They can
make a world of difference in their treatment options and how aggressive
you will be with that treatment!
But if we can't cure or control but only palliate--then
quality of life becomes paramount. Yes, there is a place for chemotherapy
and radiation therapy even if the cancer cannot be cured or controlled.
These interventions can increase quality of life by shrinking tumors, relieving
pain, opening airways, taking pressure off of spines and brains...but we
will not treat as aggressively and control of side effects will become
far more important.
Neutropenia has, in the past, been a major contributor
in the deaths of many immune compromised patients. But with new medications
and astute assessment and interventions—those numbers have been greatly
reduced in recent years. And now you can be an active soldier in the battle
The American Cancer Society
(ACS) and NCCN have teamed up to Provide Easy to Understand Information
on Cancer Treatment Options. The guidelines include information on early
detection and evaluation of cancer, staging and side effects of various
treatments. Guidelines on Fever and Neutropenia and are included
to take survey of people who have read this module--
ATAQ--Appropriate Treatment Assures Quality, an Oncology Nursing
Society Initiative for Quality Cancer Care Neutropenia training project,
Ponte Verde Beach, Florida, Sept. 23-26, 1999 Updated ATAQ
conference, Tampa, Florida, November 9, 2002
Balducci L, Lyman GH, Ozer H. "Patients aged 70+ are at high risk for
neutropenic infection and should receive hemopoietic growth factors when
treated with moderately toxic chemotherapy", Journal of
Clinical Oncology, 19:1583-1585, 2001
Balducci L, et al, "Hematopoietic reserve in the older cancer patient:
Clinical and economic considerations", Cancer Control, 7: 539-547,
Bonadonna, G, et al, "Adjuvent cyclophosphamide, methotrexate, and fluorouracil
in node-positive breast cancer: the results of 20 years of follow-up",
The New England Journal of Medicine, 332:901-906, 1995
Carroll-Johnson, R.M., editor, Selected Topics in Chemotherapy Administration,
Nursing Forum Magazine, Vol. 24, No. 1, Oncology Nursing Press, Philadelphia,
PA, Jan/Feb 1997 supplement.
Fishman, M & Mrozek-Orlowski, M, editors, Cancer Chemotherapy
Guidelines and Recommendations for Practice, 2nd edition,
Oncology Nursing Press, Philadelphia, PA, 1999.
Gates, R.A., & Fink, R.M., Oncology Nursing Secrets, Mosby,
St. Louis, MO, 1997.
Intragumtomchai, T, et al, study on pretreatment factos that predict
neutropenic complications in NHL presented at Tampa ATAQ conference 11/02--article
name unknown , Leukemia Lymphoma, 37: 351-360, 2000
Itano, J.K., Taoka, K.N., Core Curriculum for Oncology Nursing,
3rd edition, W.B. Saunders Company, Philadelphia, PA, 1998.
Jassak, PF, "Evidence Based Oncology Nursing Practice: Improving Patient
Outcomes in the Next Millenium", Oncology Nursing Forum, 28 (2),
Kwak, LW, et al, "Prognostic significance of actual dose intensity in
diffuse large-cell lymphoma: results of a tree-structured survival analysis",
of Clinical Oncology, 8:963-977, 1990
Neutropenia A-Z (Instructor's Manual), Thousand Oaks, CA, Amgen,
"Neutropenia in Blood Disorders You Don't Often Hear About (March 3,
Schindler, L.W., The Immune System—How It Works, (NIH/NCI), US
Dept. of Health and Human Services, April, 1996.
Wilson, B, "Dietary Recommendations For Neutropenic Patients", Seminars
in Oncology Nursing, Vol 18, No 1, pp44-49, Feb, 2002
Yasko, J.M., editor, Nursing Management of Symptoms Associated With
Chemotherapy, 4th edition, Meniscus Health Care Communications,
Cynwyd, PA, 1998.
Biotherapy Slide Show, ONS Online, sponsored by RP Rorer Pharmaceuticals,
Venous List, Ohio State University IV list-serv, email@example.com
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