Objectives:

1.   Define Neutropenia.
2.   Calculate an ANC and explain its significance.
3.   Outline causes and risk factors for neutropenia.
4.   Identify clinical consequences of neutropenia.
5.   Describe management strategies for neutropenia.
 
 

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:

• % neutrophils (also called polys or segs) + % bands = _______%
• Convert to decimal by dividing by 100 (ex: 48% = 48/100 = 0.48)
• 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

• Going to the site of infections, damage, or inflammation to join "the battle"
• Causing phagocytosis of particles such as bacteria

• 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.

• 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

• Patients who have been neutropenic in a previous cycle of chemo or radiation are at high risk for neutropenia in all subsequent treatments

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 for fever.

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 neutropenic.

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 if:

• 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

• 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.
• Use Chloraprep to do site care. http://www.medi-flex.com/new_site/chloraprep.shtml
• Clean out fibrin sheaths with Cath-flo (all central lines will acquire fibrin sheaths and bacteria loves to grow in this old blood) http://www.cathflo.com/cathflo/pi.html
• Consider Biopatch at site of immunocompromised patient's central lines. http://ecatalog.ethicon.com/ec_ecatalog/SkinAndWoundCare/Content/CAT_128.htm in "Advanced Wound Care Product Catalog"
• (Visit the links to the above sites to learn more about each of these products)

• 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
• pneumonia
• 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)

• Avoid enemas, rectal temperatures, and anything "invasive" if possible.

• 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 often...
• 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
• Daily bath
• 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 and water.
• 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 this low...

• 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...

• 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 "scoop poop".
• 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 the 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...

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

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!
 
 

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.

 Neupogen info  at: www.neupogen.com (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 Neutropenia)

• FDA approvals
• Patients with cancer receiving myelosuppressive chemotherapy
• Patients with AML (Acute Myelogenous Leukemia) receiving induction or consolidation chemotherapy
• Patients with cancer receiving bone marrow transplant (BMT)
• 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)
• Use prefilled syringe of 480 mcg if > 132 pounds and < 211 pounds
• Increase by 5 mcg/kg in next cycle if desired ANC was not achieved
• 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)

• FDA approvals
• AML following induction chemotherapy in older adults (> 55 years)
• BMT
• 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 the nadir

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.

• FDA approval
• 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 is due

• 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 are:

• 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.)

• Make sure that these growth factors are correctly prescribed and used

Determine what your patient's actual goals are with treatment:

• Are they going for "the gold"--a cure from cancer?
• Or is cure not possible?
• 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 some quality?

• 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 as possible!
• 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 it all...
• 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...)

• 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 against neutropenia!
 

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 at: http://www.cancer.org/docroot/ETO/ETO_10.asp?sitearea=ETO
 
 

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, 2000

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, Oncology 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, 2^nd 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, 3^rd 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), 3-4, 2001

Kwak, LW, et al, "Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: results of a tree-structured survival analysis", Journal of Clinical Oncology, 8:963-977, 1990

Neutropenia A-Z (Instructor's Manual), Thousand Oaks, CA, Amgen, Inc, 2002

"Neutropenia in Blood Disorders You Don't Often Hear About (March 3, 2001):http://www.neutropenia.ca/what/html

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, 4^th edition, Meniscus Health Care Communications, Cynwyd, PA, 1998.

Biotherapy Slide Show, ONS Online, sponsored by RP Rorer Pharmaceuticals, www.rp-rorer.com/productinfo/slides/general-oncology/HTMLslides

Venous List, Ohio State University IV list-serv, www.venous@ohsu.com
 
 

Don’t forget to take the test and do the evaluation if you want contact hours…

This is a practice test. You should try and pass this one before taking the real test to submit for your certificate. To pass this test you will need at least 8 out of 10 correct. After passing this practice test scroll down for the real test to submit your score to receive your certificate by e-mail.

Question # 1 (True/False) Only cancer patients have to worry about neutropenia.
True
False

Question # 2 (True/False) Neutrophils are precursors to white blood cells.
True
False

Question # 3 (True/False) The Nadir is the lowest point that the patient's blood counts can get to after chemotherapy.
True
False

Question # 4 (True/False) The patient should wait to report fever until it is > 102 F.
True
False

Question # 5 (True/False) In a severely neutropenic patient - fever may be their only symptom of infection.
True
False

Question # 6 (Multiple Choice) A patient with an ANC of 750 is said to be:
A. Mildly neutropenic
B. Moderately neutropenic
C. Severely neutropenic
D. Not neutropenic at all

Question # 7 (Multiple Choice) Neutropenic precautions include:
A. Good handwashing
B. Good hygiene
C. Avoiding exposure to people who are sick or have been exposed to infectious diseases
D. All of the above

Question # 8 (True/False) Avoiding fresh fruits and vegetables and plants when neutropenic is controversial.
True
False

Question # 9 (Multiple Choice) A medication that has made a significant improvement in the severity and length of neutropenia is:
A. Neupogen
B. Procrit
C. Sargramostim
D. All of the above

Question # 10 (Multiple Choice) Mr. "Neut" Gingrich has a WBC of 2500 with segs of 12% and bands of 3%. What is his ANC?
A. 337500
B. 1050
C. 375
D. None of the above

RealNurseEd.com

(Cynthia F. Cramer, BA, RN, OCN)

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