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{{ Neutropenia }} | {{ Neutropenia }} | ||
{{CMG}} {{AE}} {{DG}} | {{CMG}}; {{AE}} {{DG}} | ||
==Overview== | ==Overview== | ||
'''Neutropenia''' is a [[Hematology|hematological]] disorder characterized by an abnormally low number of [[neutrophil granulocyte]]s (a type of [[white blood cell]]). Neutrophils usually make up 50-70% of circulating white blood cells and serve as the primary defense against [[infection]]s by destroying [[bacterium|bacteria]] in the [[blood]]. Hence, patients with neutropenia are more susceptible to bacterial infections and without prompt medical attention, the condition may become life-threatening. Neutropenia can be [[Acute (medical)|acute]] or [[chronic (medicine)|chronic]] depending on the duration of the illness. A patient has chronic neutropenia if the condition lasts for greater than 3 months. It is sometimes used interchangeably with the term [[leukopenia]]. However, neutropenia is more properly considered a subset of leukopenia as a whole. Some patients, such as those with constitutional/benign ethnic neutropenia, suffer relatively few complications, however neutropenia related to cytotoxic chemotherapy, [[hematopoietic stem cell]] transplant, or other causes of bone marrow suppression may present as a medical emergency. | '''[[Neutropenia]]''' is a [[Hematology|hematological]] disorder characterized by an abnormally low number of [[neutrophil granulocyte]]s (a type of [[white blood cell]]). Neutrophils usually make up 50-70% of circulating white blood cells and serve as the primary defense against [[infection]]s by destroying [[bacterium|bacteria]] in the [[blood]]. Hence, patients with neutropenia are more susceptible to bacterial infections and without prompt medical attention, the condition may become life-threatening. Neutropenia can be [[Acute (medical)|acute]] or [[chronic (medicine)|chronic]] depending on the duration of the illness. A patient has chronic neutropenia if the condition lasts for greater than 3 months. It is sometimes used interchangeably with the term [[leukopenia]]. However, neutropenia is more properly considered a subset of leukopenia as a whole. Some patients, such as those with constitutional/benign ethnic neutropenia, suffer relatively few complications, however neutropenia related to [[cytotoxic]] [[chemotherapy]], [[hematopoietic stem cell]] transplant, or other causes of [[bone marrow suppression]] may present as a medical emergency. | ||
== Classification == | ==Historical Perspective== | ||
Calculated based on blood count differential, neutropenia is defined as an absolute neutrophil count (ANC) less than 1,500 cells per microliter and is calculated by multiplying the total white blood cell (WBC) count by the percentage of neutrophils (including both mature neutrophils and band forms). | [[Neutropenia]] was first noted around the start of the 20th century on review of blood cell differentials described in patients with [[lupus]], other [[autoimmune disorders]], and with various drug toxicities.<ref name="NLMID39120200R">{{cite journal |author=Dameshek W. |title=Leukopenia and Agranulocytosis.|journal=Oxford University Press. |volume=1|pages=841-52|year=1944|NLM ID 39120200R}}</ref> | ||
==Classification== | |||
Calculated based on blood count differential, neutropenia is defined as an [[absolute neutrophil count]] (ANC) less than 1,500 cells per microliter and is calculated by multiplying the total white blood cell (WBC) count by the percentage of neutrophils (including both mature neutrophils and band forms). | |||
* '''Mild Neutropenia:''' ANC 1,000-1500 cells/microliter | * '''Mild Neutropenia:''' ANC 1,000-1500 cells/microliter | ||
* '''Moderate Neutropenia:''' ANC 500-1000 cells/microliter | * '''Moderate Neutropenia:''' ANC 500-1000 cells/microliter | ||
* '''Severe Neutropenia (Agranulocytosis):''' ANC <500 cells/microliter | * '''Severe Neutropenia ([[Agranulocytosis]]):''' ANC <500 cells/microliter | ||
==Pathophysiology== | ==Pathophysiology== | ||
| Line 17: | Line 20: | ||
# '''Impaired granulocyte production''' | # '''Impaired granulocyte production''' | ||
#* Hematologic malignancy with bone marrow infiltration | #* [[Hematologic]] [[malignancy]] with bone marrow infiltration | ||
#* Myelosuppressive chemotherapy or other medications that are toxic to the bone marrow | #* Myelosuppressive [[chemotherapy]] or other medications that are toxic to the bone marrow | ||
#* Nutritional deficiencies | #* Nutritional deficiencies | ||
# '''Margination:''' (process where free flowing blood cells exit circulation) | # '''Margination:''' (process where free flowing blood cells exit circulation) | ||
#* Splenic sequestration | #* Splenic sequestration | ||
#* Adherence to the vascular endothelium | #* Adherence to the vascular [[endothelium]] | ||
# '''Peripheral destruction''' | # '''Peripheral destruction''' | ||
#* Autoimmune [[hemolysis]] | #* Autoimmune [[hemolysis]] | ||
| Line 28: | Line 31: | ||
==Causes== | ==Causes== | ||
The most common etiologies are constitutional or benign ethnic neutropenia (BEN) and drug-induced neutropenia. | The most common etiologies are constitutional or benign ethnic neutropenia (BEN) and drug-induced neutropenia. While the former is typically benign, as the title suggests, and not associated with significant complications, drug-induced neutropenia is often related to underlying cancer or medications that can suppress the bone marrow and can be severe and life-threatening if not identified and treated urgently. | ||
==Epidemiology and Demographics== | |||
Neutropenia is typically identified in at-risk patients undergoing [[cytotoxic]] [[chemotherapy]] or on other myelosuppressive medications. As noted above, some ethnicities have an unusually high prevalence of incidentally identified mild neutropenia, also termed constitutional or benign ethnic neutropenia (BEN). This is most common in blacks, Yemenites, West Indians, and Arab Jordanians and is suggested to be caused by a mutation in the [[Duffy antigen]] on red blood cells that helps to confer resistance to [[malaria]]. As the name suggests, these cases are typically mild and do not result in immunosuppression. | |||
== | ==Screening== | ||
There are no routine screening recommendations for [[neutropenia]]. [[Neutropenia]] is typically identified incidentally on routine blood work or while monitoring after [[cytotoxic]] therapy. | |||
==Natural History, Complications and Prognosis== | |||
[[Neutropenia]] is a frequent finding on blood differential. When identified, attention must be placed on identifying underlying medication toxicities, [[autoimmune disorders]] or hematological malignancies, or various infections. While most patients with mild neutropenia recover quickly and without complications, severe medication-related neutropenia can be fatal in up to 10%.<ref name="PMID18043241">{{cite journal |author=Andrès E, Maloisel F. |title=Idiosyncratic drug-induced agranulocytosis or acute neutropenia. |journal=Curr Opin Hematol. |volume=15|issue=1 |pages=15-21 |year=2008|pmid=18043241 |doi=|url=https://www.ncbi.nlm.nih.gov/pubmed/18043241}}</ref> Close attention must be given to identifying poor prognostic indicators, early signs of infection, and any cyclic pattern to this hematologic abnormality to avoid potentially fatal complications. | |||
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[[Febrile neutropenia]] is an often fatal complication of severe neutropenia, with fever often being the only presenting symptom of an underlying infection. | |||
==Diagnosis== | |||
In patients with severe [[neutropenia]], the neutrophil-mediated inflammatory process in the setting of infection is often blunted. Fever can be the sole presenting symptom. The risk of infection increases with the degree and duration of neutropenia with prolonged neutropenia defined as >7 days. | |||
Per 2002 IDSA <ref name="PMID21258094">{{cite journal |author=Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR; Infectious Diseases Society of America. |title=Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america|journal=Clin Infect Dis. |volume=52 |issue=4 |pages=e56-95 |year=2011 |pmid=21258094 |doi=|url=http://www.ncbi.nlm.nih.gov/pubmed/21258094}}</ref> and 2013 ASCO <ref name="PMID23319691">{{cite journal |author=Flowers CR, Seidenfeld J, Bow EJ, Karten C, Gleason C, Hawley DK, Kuderer NM, Langston AA, Marr KA, Rolston KV, Ramsey SD |title=Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline=J Clin Oncol. |volume=31 |issue=6 |pages=794-810 |year=2013 |pmid=23319691 |doi=|url=http://www.ncbi.nlm.nih.gov/pubmed/23319691}}</ref> guidelines, [[febrile neutropenia]] requires both of the following criteria: | |||
#[[Fever]]: single oral temperature >38.3 C/101 F or sustained temperature >38 C/100.4 F for 1 hour.''' | |||
#Severe neutropenia: ANC< 500 cells/microliter.''' | |||
==History and Symptoms== | ===History and Symptoms=== | ||
Neutropenia can go undetected until the patient develops secondary, and often severe, [[infection]]s or [[sepsis]]. Some common infections can take an unexpected course in neutropenic patients; formation of [[pus]], for example, can be notably absent, as this requires circulating neutrophil granulocytes. | [[Neutropenia]] can go undetected until the patient develops secondary, and often severe, [[infection]]s or [[sepsis]]. Some common infections can take an unexpected course in neutropenic patients; formation of [[pus]], for example, can be notably absent, as this requires circulating neutrophil granulocytes. | ||
History should focus on symptoms suggestive of malignancy or infections, patient or family history of autoimmune or [[immunodeficiency]] disorders, risk factors for infections including [[HIV]] and [[hepatitis]], and any unusual dietary practices or history of [[bariatric surgery]]. Medications should be reviewed with particular attention to chemotherapeutics, antibiotics, [[antiepileptics]], and psychoactive drugs as well as documenting any new medications started within the preceding few months. | History should focus on symptoms suggestive of malignancy or infections, patient or family history of autoimmune or [[immunodeficiency]] disorders, risk factors for infections including [[HIV]] and [[hepatitis]], and any unusual dietary practices or history of [[bariatric surgery]]. Medications should be reviewed with particular attention to chemotherapeutics, antibiotics, [[antiepileptics]], and psychoactive drugs as well as documenting any new medications started within the preceding few months. | ||
Common presenting symptoms in neutropenic patients include: | Common presenting symptoms in neutropenic patients include: | ||
| Line 636: | Line 67: | ||
*Shaking [[chills]] | *Shaking [[chills]] | ||
==Physical Examination== | ===Physical Examination=== | ||
A rectal examination should not be performed in a patient with neutropenia. | Physical examination should focus on identifying any potential signs of [[infection]] and is directed by the patients' presenting symptoms. A rectal examination should not be performed in a patient with [[neutropenia]]. | ||
== | ===Laboratory Findings=== | ||
[[Neutropenia]] is detected on a full blood count. A peripheral [[blood smear]] is often useful to evaluate for abnormal morphology of the visible cells, which may help suggest the underlying cause. Additional laboratory studies include evaluation of metabolic abnormalities, genetic causes neutropenia, and toxic causes. | |||
===Imaging Findings=== | |||
[[Neutropenia]] is not identified on or correlated with any particular imaging. In the cases of [[neutropenic fever]], imaging findings are dependent upon the source of the [[fevers]]. Initial evaluation for neutropenic fever should include chest radiography to evaluate for pulmonary infiltrates or effusions. Further imaging, such as CT or MRI scans, are indicated depending upon presenting symptoms and physical examination findings. | |||
===Other Diagnostic Studies=== | |||
Other diagnostic studies for [[neutropenia]] include [[bone marrow biopsy]], which may be helpful when the etiology is uncertain, or serious causes such as [[malignancy]] and marrow replacement are suspected. | |||
==Treatment== | |||
===Medical Therapy=== | |||
There is no specific therapy for [[neutropenia]] itself aside from removing the offending agents in drug-induced cases and treating the underlying disease in other, however recombinant [[Granulocyte-colony stimulating factor|G-CSF]] (granulocyte-colony stimulating factor) can be considered to speed myeloid reconstitution. | |||
Asymptomatic, mild to moderate neutropenia can often be monitored closely on an outpatient basis with serial CBCs and evaluation for medications, infections, or alternative sources of neutropenia as described in detail above. Offending medications are often held and the patient is monitored for response to discontinuation while evaluating for alternative, more concerning etiologies. With mild neutropenia, medications can often be reintroduced after neutrophil counts recover as the neutropenia is typically dose-dependent. | |||
Patients who are febrile, acutely ill, or with severe neutropenia often warrant urgent hospitalization for close monitoring and treatment. Offending medications must be discontinued as drug-induced [[agranulocytosis]] presents up to a 10% mortality and is very likely to recur if the offending agent is restarted. | |||
===Complications=== | |||
There are no intrinsic complications of [[neutropenia]], however people who are neutropenic are at risk for infections and [[febrile neutropenia]]. | |||
====Febrile Neutropenia==== | |||
:'''Low risk patients:''' ANC>100 cells/microliter, normal liver and renal function, normal chest x-ray, no evidence of central line infection, MASCC >21, and duration of neutropenia expected <7 days in a patient with close monitoring and access to medical care. | |||
::* [[Ciprofloxacin]] 500mg PO BID + amoxicillin/clavulanate 500mg PO TID | |||
:'''High risk patients:''' Hospitalize and initiate empiric parenteral antimicrobial therapy. IDSA guidelines recommend initial monotherapy as below. | |||
::* [[Cefepime]] 2 g IV Q8H | |||
::* [[Meropenem]] 1 g IV Q8H | |||
::* [[Imipenem]]/cilastatin 500 mg IV Q6H | |||
::* [[Piperacillin]]/tazobactam 4.5 g IV Q6H | |||
::* [[Ceftazidime]] 2 g IV Q8H (recent data shows increasing resistance to ceftazidime and inferior Gram-positive coverage to alternative regimens) | |||
:'''Indications for resistant Gram-positive coverage:''' Vancomycin or linezolid is NOT recommended as part of initial treatment unless one of the following is present and, if started, should be discontinued after 2-3 days if there is no evidence of Gram-positive infection. | |||
: | ::* Hemodynamic instability | ||
:* | ::* Suspected catheter-associated infection | ||
:* | ::* [[Mucositis]] or cellulitis | ||
:* | ::* [[Pneumonia]] | ||
:* | ::* History of [[MRSA]] infection or colonization | ||
::* Gram-positive [[bacteremia]] prior to final culture results | |||
::* Recent [[fluoroquinolone]] [[prophylaxis]] | |||
:'''Persistent Fever:''' Continue empiric therapy until either culture data is available to direct management or after 3-5 days if the patient fails to improve. The median time to defercescence in adequately treated patients is 5 days with hematologic malignancies and 2-3 days with solid tumors. If the patient is still febrile or develops recurrent fevers after this time period further work up is suggested. | |||
:# Re-evaluate sources of infection | |||
:# Re-evaluate indications for resistant [[Gram-positive]] coverage and consider adding [[vancomycin]] or [[linezolid]]. | |||
:# Re-evaluate indications for resistant [[Gram-negative]] organisms and [[anaerobes]] and consider broadening to [[carbapenem]] antibiotics. | |||
:# Consider [[fungal]] coverage in high risk patients if fevers persist after 4-7 days of appropriate antibiotic coverage and duration of neutropenia is expected to last >7 days. :Consider the following antifungals. | |||
:#* [[Caspofungin]] 70 mg IV x 1 dose, then 50mg IV daily | |||
:#* Liposomal [[Amphotericin]] B 3 mg/kg/day | |||
:#* [[Voriconazole]] 6 mg/kg IV Q12H x 2 doses, then 4 mg/kg IV Q12H | |||
:::Caspofungin provides excellent coverage for [[Candida]] and is well tolerated, however nodular pulmonary infiltrates warrant coverage of [[Aspergillus]] with Voriconazole or Amphotericin B as [[echinocandins]] do not provide adequate coverage of Aspergillus or [[endemic]] fungi. | |||
:'''Duration of Antimicrobials''' <br/> | |||
: | ::*Documented infection: Continue antimicrobials as directed by culture data. Continue treatment for the standard duration for that particular infection and until myeloid recovery (ANC>500 cells/microliter). If counts recover prior to completing the treatment course, consider transition to an oral regimen guided by culture data. <br/> | ||
:* | ::*Negative Cultures: Continue empiric antimicrobial regimen until myeloid recovery (ANC>500 cells/microliter). If afebrile with no evidence of ongoing infection, consider transition to oral regimen (e.g. Ciprofloxacin + [[Amoxicillin]]/Clavulanate) and continue until myeloid recovery. | ||
: | |||
===Surgery=== | |||
There are no surgical treatments for [[neutropenia]]. In patients' with [[neutropenic fever]], surgical intervention may be necessary depending on the sources of their infections. | |||
=== | ===Primary Prevention=== | ||
Prevention of neutropenia is dependent upon avoiding certain medications or treatment of underlying conditions. | |||
===Secondary Prevention=== | |||
Secondary prevention of neutropenia relies on careful avoidance of triggers, such as certain medications, or treatment of underlying conditions. Further discussion of the causes of neutropenia are reviewed above. | |||
=== | |||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
[[Category:Dermatology]] | |||
[[Category: | |||
[[Category:Hematology]] | [[Category:Hematology]] | ||
[[Category:Hepatology]] | |||
{{WS}} | |||
{{WH}} | {{WH}} | ||
Latest revision as of 23:39, 16 November 2016
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Neutropenia overview On the Web |
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American Roentgen Ray Society Images of Neutropenia overview |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Daniel A. Gerber, M.D. [2]
Overview
Neutropenia is a hematological disorder characterized by an abnormally low number of neutrophil granulocytes (a type of white blood cell). Neutrophils usually make up 50-70% of circulating white blood cells and serve as the primary defense against infections by destroying bacteria in the blood. Hence, patients with neutropenia are more susceptible to bacterial infections and without prompt medical attention, the condition may become life-threatening. Neutropenia can be acute or chronic depending on the duration of the illness. A patient has chronic neutropenia if the condition lasts for greater than 3 months. It is sometimes used interchangeably with the term leukopenia. However, neutropenia is more properly considered a subset of leukopenia as a whole. Some patients, such as those with constitutional/benign ethnic neutropenia, suffer relatively few complications, however neutropenia related to cytotoxic chemotherapy, hematopoietic stem cell transplant, or other causes of bone marrow suppression may present as a medical emergency.
Historical Perspective
Neutropenia was first noted around the start of the 20th century on review of blood cell differentials described in patients with lupus, other autoimmune disorders, and with various drug toxicities.[1]
Classification
Calculated based on blood count differential, neutropenia is defined as an absolute neutrophil count (ANC) less than 1,500 cells per microliter and is calculated by multiplying the total white blood cell (WBC) count by the percentage of neutrophils (including both mature neutrophils and band forms).
- Mild Neutropenia: ANC 1,000-1500 cells/microliter
- Moderate Neutropenia: ANC 500-1000 cells/microliter
- Severe Neutropenia (Agranulocytosis): ANC <500 cells/microliter
Pathophysiology
Neutropenia develops as a result of one of the three following mechanisms:
- Impaired granulocyte production
- Hematologic malignancy with bone marrow infiltration
- Myelosuppressive chemotherapy or other medications that are toxic to the bone marrow
- Nutritional deficiencies
- Margination: (process where free flowing blood cells exit circulation)
- Splenic sequestration
- Adherence to the vascular endothelium
- Peripheral destruction
Causes
The most common etiologies are constitutional or benign ethnic neutropenia (BEN) and drug-induced neutropenia. While the former is typically benign, as the title suggests, and not associated with significant complications, drug-induced neutropenia is often related to underlying cancer or medications that can suppress the bone marrow and can be severe and life-threatening if not identified and treated urgently.
Epidemiology and Demographics
Neutropenia is typically identified in at-risk patients undergoing cytotoxic chemotherapy or on other myelosuppressive medications. As noted above, some ethnicities have an unusually high prevalence of incidentally identified mild neutropenia, also termed constitutional or benign ethnic neutropenia (BEN). This is most common in blacks, Yemenites, West Indians, and Arab Jordanians and is suggested to be caused by a mutation in the Duffy antigen on red blood cells that helps to confer resistance to malaria. As the name suggests, these cases are typically mild and do not result in immunosuppression.
Screening
There are no routine screening recommendations for neutropenia. Neutropenia is typically identified incidentally on routine blood work or while monitoring after cytotoxic therapy.
Natural History, Complications and Prognosis
Neutropenia is a frequent finding on blood differential. When identified, attention must be placed on identifying underlying medication toxicities, autoimmune disorders or hematological malignancies, or various infections. While most patients with mild neutropenia recover quickly and without complications, severe medication-related neutropenia can be fatal in up to 10%.[2] Close attention must be given to identifying poor prognostic indicators, early signs of infection, and any cyclic pattern to this hematologic abnormality to avoid potentially fatal complications.
Febrile neutropenia is an often fatal complication of severe neutropenia, with fever often being the only presenting symptom of an underlying infection.
Diagnosis
In patients with severe neutropenia, the neutrophil-mediated inflammatory process in the setting of infection is often blunted. Fever can be the sole presenting symptom. The risk of infection increases with the degree and duration of neutropenia with prolonged neutropenia defined as >7 days.
Per 2002 IDSA [3] and 2013 ASCO [4] guidelines, febrile neutropenia requires both of the following criteria:
- Fever: single oral temperature >38.3 C/101 F or sustained temperature >38 C/100.4 F for 1 hour.
- Severe neutropenia: ANC< 500 cells/microliter.
History and Symptoms
Neutropenia can go undetected until the patient develops secondary, and often severe, infections or sepsis. Some common infections can take an unexpected course in neutropenic patients; formation of pus, for example, can be notably absent, as this requires circulating neutrophil granulocytes. History should focus on symptoms suggestive of malignancy or infections, patient or family history of autoimmune or immunodeficiency disorders, risk factors for infections including HIV and hepatitis, and any unusual dietary practices or history of bariatric surgery. Medications should be reviewed with particular attention to chemotherapeutics, antibiotics, antiepileptics, and psychoactive drugs as well as documenting any new medications started within the preceding few months.
Common presenting symptoms in neutropenic patients include:
- Fever
- Frequent infections due to lessened ability to fight bacterial infections
- Mouth ulcers
- Diarrhea
- Burning sensation when urinating
- Unusual redness, pain, or swelling around a wound
- Sore throat
- Shortness of breath
- Shaking chills
Physical Examination
Physical examination should focus on identifying any potential signs of infection and is directed by the patients' presenting symptoms. A rectal examination should not be performed in a patient with neutropenia.
Laboratory Findings
Neutropenia is detected on a full blood count. A peripheral blood smear is often useful to evaluate for abnormal morphology of the visible cells, which may help suggest the underlying cause. Additional laboratory studies include evaluation of metabolic abnormalities, genetic causes neutropenia, and toxic causes.
Imaging Findings
Neutropenia is not identified on or correlated with any particular imaging. In the cases of neutropenic fever, imaging findings are dependent upon the source of the fevers. Initial evaluation for neutropenic fever should include chest radiography to evaluate for pulmonary infiltrates or effusions. Further imaging, such as CT or MRI scans, are indicated depending upon presenting symptoms and physical examination findings.
Other Diagnostic Studies
Other diagnostic studies for neutropenia include bone marrow biopsy, which may be helpful when the etiology is uncertain, or serious causes such as malignancy and marrow replacement are suspected.
Treatment
Medical Therapy
There is no specific therapy for neutropenia itself aside from removing the offending agents in drug-induced cases and treating the underlying disease in other, however recombinant G-CSF (granulocyte-colony stimulating factor) can be considered to speed myeloid reconstitution.
Asymptomatic, mild to moderate neutropenia can often be monitored closely on an outpatient basis with serial CBCs and evaluation for medications, infections, or alternative sources of neutropenia as described in detail above. Offending medications are often held and the patient is monitored for response to discontinuation while evaluating for alternative, more concerning etiologies. With mild neutropenia, medications can often be reintroduced after neutrophil counts recover as the neutropenia is typically dose-dependent.
Patients who are febrile, acutely ill, or with severe neutropenia often warrant urgent hospitalization for close monitoring and treatment. Offending medications must be discontinued as drug-induced agranulocytosis presents up to a 10% mortality and is very likely to recur if the offending agent is restarted.
Complications
There are no intrinsic complications of neutropenia, however people who are neutropenic are at risk for infections and febrile neutropenia.
Febrile Neutropenia
- Low risk patients: ANC>100 cells/microliter, normal liver and renal function, normal chest x-ray, no evidence of central line infection, MASCC >21, and duration of neutropenia expected <7 days in a patient with close monitoring and access to medical care.
- Ciprofloxacin 500mg PO BID + amoxicillin/clavulanate 500mg PO TID
- High risk patients: Hospitalize and initiate empiric parenteral antimicrobial therapy. IDSA guidelines recommend initial monotherapy as below.
- Cefepime 2 g IV Q8H
- Meropenem 1 g IV Q8H
- Imipenem/cilastatin 500 mg IV Q6H
- Piperacillin/tazobactam 4.5 g IV Q6H
- Ceftazidime 2 g IV Q8H (recent data shows increasing resistance to ceftazidime and inferior Gram-positive coverage to alternative regimens)
- Indications for resistant Gram-positive coverage: Vancomycin or linezolid is NOT recommended as part of initial treatment unless one of the following is present and, if started, should be discontinued after 2-3 days if there is no evidence of Gram-positive infection.
- Hemodynamic instability
- Suspected catheter-associated infection
- Mucositis or cellulitis
- Pneumonia
- History of MRSA infection or colonization
- Gram-positive bacteremia prior to final culture results
- Recent fluoroquinolone prophylaxis
- Persistent Fever: Continue empiric therapy until either culture data is available to direct management or after 3-5 days if the patient fails to improve. The median time to defercescence in adequately treated patients is 5 days with hematologic malignancies and 2-3 days with solid tumors. If the patient is still febrile or develops recurrent fevers after this time period further work up is suggested.
- Re-evaluate sources of infection
- Re-evaluate indications for resistant Gram-positive coverage and consider adding vancomycin or linezolid.
- Re-evaluate indications for resistant Gram-negative organisms and anaerobes and consider broadening to carbapenem antibiotics.
- Consider fungal coverage in high risk patients if fevers persist after 4-7 days of appropriate antibiotic coverage and duration of neutropenia is expected to last >7 days. :Consider the following antifungals.
- Caspofungin 70 mg IV x 1 dose, then 50mg IV daily
- Liposomal Amphotericin B 3 mg/kg/day
- Voriconazole 6 mg/kg IV Q12H x 2 doses, then 4 mg/kg IV Q12H
- Caspofungin provides excellent coverage for Candida and is well tolerated, however nodular pulmonary infiltrates warrant coverage of Aspergillus with Voriconazole or Amphotericin B as echinocandins do not provide adequate coverage of Aspergillus or endemic fungi.
- Duration of Antimicrobials
- Documented infection: Continue antimicrobials as directed by culture data. Continue treatment for the standard duration for that particular infection and until myeloid recovery (ANC>500 cells/microliter). If counts recover prior to completing the treatment course, consider transition to an oral regimen guided by culture data.
- Negative Cultures: Continue empiric antimicrobial regimen until myeloid recovery (ANC>500 cells/microliter). If afebrile with no evidence of ongoing infection, consider transition to oral regimen (e.g. Ciprofloxacin + Amoxicillin/Clavulanate) and continue until myeloid recovery.
- Documented infection: Continue antimicrobials as directed by culture data. Continue treatment for the standard duration for that particular infection and until myeloid recovery (ANC>500 cells/microliter). If counts recover prior to completing the treatment course, consider transition to an oral regimen guided by culture data.
Surgery
There are no surgical treatments for neutropenia. In patients' with neutropenic fever, surgical intervention may be necessary depending on the sources of their infections.
Primary Prevention
Prevention of neutropenia is dependent upon avoiding certain medications or treatment of underlying conditions.
Secondary Prevention
Secondary prevention of neutropenia relies on careful avoidance of triggers, such as certain medications, or treatment of underlying conditions. Further discussion of the causes of neutropenia are reviewed above.
References
- ↑ Dameshek W. (1944). "Leukopenia and Agranulocytosis". Oxford University Press. 1: 841–52. Text "NLM ID 39120200R" ignored (help)
- ↑ Andrès E, Maloisel F. (2008). "Idiosyncratic drug-induced agranulocytosis or acute neutropenia". Curr Opin Hematol. 15 (1): 15–21. PMID 18043241.
- ↑ Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR; Infectious Diseases Society of America. (2011). "Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america". Clin Infect Dis. 52 (4): e56–95. PMID 21258094.
- ↑ Flowers CR, Seidenfeld J, Bow EJ, Karten C, Gleason C, Hawley DK, Kuderer NM, Langston AA, Marr KA, Rolston KV, Ramsey SD (2013). "Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline=J Clin Oncol". 31 (6): 794–810. PMID 23319691.