Post on 24-Dec-2015
transcript
Cat Hathaway
Neutropenia Definition of neutropenia is ANC <1500
cells/mm3
African american patients can have ANC of 1000 cells/mm3 w/o complications
Severity of neutropenia determines the risk of infection. Mild is 1000-1500, Moderate 500-1000, and severe <500
Neutropenia increases risk of bacterial/suppurative infections. Not parasitic or viral infections.
The neutrophil About 60 billion PMNs are produced
DAILY! An equal number are circulating in the blood, the half life is 6-8 hrs.Neutropenia occurs if bone marrow
production lags behind the amount in circulation, from destruction, ineffective granulopoeisis, or shifts into tissue pools/vascular endothelium
Integral in fighting infection of pyogenic bacteria, enteric bacteria, and some fungi
Consequences of Neutropenia Drug induced granulocytopenia incurs 6-
10% mortality rate Cancer patients with neutropenic fever
have 4-30% mortality rate21% patients with cancer and neutropenic
fever will have serious complications Patients with ANC <500 will develop
severe infxn within 1-4 weeks, ANC <1000 is associated with less risk, but still substantial compared to norms
Congenital neutropenias Neutropenias associated with immune defects Congenital neutropenia due to mutations
Cyclic neutropeniaKostmann Syndrome (Severe Congenital
Neutropenia) – Typically die in early childhood Chronic benign neutropenia Neutropenia w/ phenotypic abnormalities
Shwachman-diamond-oski syndromeCartilage-hair hypoplasia syndromeDyskeratosis congenitaBarth SyndromeChediak Higashi syndrome
Congential neutropenia
Benign familial neutropeniaDon’t mount leukocytosis to infection, but
are able to mount fever and inflammatory response. Not associated with higher infection incidence
Myeloperoxidase deficiencyNot a real neutropenia, lab error because
some labs identify neutrophils based on presence of myeloperoxidase
Cyclic neutropenia Typically autosomal dominant Found to be due to germline mutations in
ELA2ELA2 encodes neutrophil elastase. Interestingly this
protein in molecular studies seems to be an oncoprotein
Kostmann syndrome also assoc with ELA2 mutations and GCSF-r mutations and in 10 yrs 21% will go on to develop MDS and or AML
Counts cycle every 21 days with nadirs close to 0 and peaks near normal
Length of nadir relates to infxs complications
Acquired Neutropenia Infections (most common)
HIV, erhlichia, parasites, parvo B19, EBV, HepB, HCV Nutritional deficiency
B12, copper, folate Drugs/chemicals/chemo (1-3.4 cases/million/yr)
Antithyroid, macrolides, procainamide, sulfonamidesClozapine causes agranulocytosis in 1% of patients, but
appears to be genetic not immune Immunologic due to BMT or blood tx Felty Syndrome (RA, splenomegaly, neutropenia) Splenic sequestration Complement activation (2/2 ECMO, HD,
cardiopulmonary bypass, etc)
Other differentials Leukemia (CLL, CML, ALL, AML, hairy cell) Lymphoma (Hodgkin, NonHodgkin) T-LGL – indolent, responds well to
immunosuppression PNH Bone marrow failure, MDS MM Autoimmune Neutropenia (Primary and
Secondary)SLE, RA are assoc with secondary AINPrimary AIN typically presents in early childhood
Work up CBC with diff B12, folate Infectious workup (if fever present)
Bcx, ucx, cxr, sputum cx Bone marrow biopsy
Esp if anemia/thrombocytopenia also presentCan evaluate for maturation arrest, fungal
infection, marrow defect, b12/folate deficiency Testing for neutrophil antibodies can be
done, but is difficult and false positives and false negatives are common
Neutrophil Antibody Assays GIFT (granulocyte immunofluorescent
test) – indirect assay using patient’s serum and banked normal PMNs
GAT (granulocyte agglutination test)Normal PMNs incubated with serum from pt
Tests are difficult secondary to HLA alloantibodies and immune complexesTherefore in routine practice these tests are
not recommended
Medications/Treatment Depends on etiology of neutropenia
Drug related, remove offending agent.Viral related, no treatment typically
necessary Avoid rectal exams/give stool softener Neutropenic diet (no fresh fruit/veg) If fever present then broad spectrum abx For chemo related or cyclic neutropenia
often tx with GCSF agents
Treatment continued Primary AIN
Typically not associated with severe infections and often only treated symptomatically for infections w/ abx
Secondary AINOften assoc with SLE/RA – can use GCSF but
have to be careful because this can lead to disease flares and leukocytoclastic vasculitis
Infections due to neutropeniaManagement of underlying infxn, supportive
abx/treatment
Chemotherapy induced neutropenia In patients who have developed prior
episodes of neutropenia, often will presumptively treat with GCSF as they are at higher risk for recurrent neutropenia
In patients with risk of 20% or more for neutropenia following treatment primary prophylaxis with GCSF may be indicated
Danger on the road
Resources Neutropenia: Differential Diagnoses & Workup. Author: John E Godwin, MD, MS, Professor of
Medicine, Chief Division of Hematology/Oncology, Associate Director, Simmons Cooper Cancer Institute, Southern Illinois University School of Medicine Coauthor(s): Christopher D Braden, DO, Attending Physician, Department of Hematology and Oncology, St. Francis Cancer Center, Indianapolis, Indiana. Updated: Oct 16, 2008. Accessed 9/7/09.
Hematology 2004 The American Society of Hematology. Congenital and Acquired Neutropenia Nancy Berliner, Marshall Horwitz and Thomas P. Loughran Jr.
Clinical Cornerstone Volume 8, Supplement 5, 2006, Pages S5-S11 Neutropenia: Overview and Current Therapies
Congenital neutropenia Robert L Baehner, MD, Last literature review version 17.2: May 2009 | This topic last updated: March 29, 2009. Accessed 9/9/09
Overview of neutropenia Robert L Baehner, MD, Last literature review version 17.2: May 2009 | This topic last updated: February 19, 2009. Accessed 9/9/09