Episode 011: Cytopenias Series Pt. 3 - Neutropenia

The Fellow on Call: The Heme/Onc Podcast

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Neutripena - What's Normal and Abnormal?

There are medication induced nutripena, drug induced neutrip na. The most notable culprit for drug induce neutripena is cimotherapy. Knowing that the cancer patient may have got en cimo, find out when they got their last cycle of emo will be incredibly helpful in treating this condition. And then we're going to talk about the more complicated causes of neutripenia so he can explain them a little better.

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In our final stop in our Cytopenias series, we discuss the ins and outs of neutropenia. This is another very commonly seen issue in the clinic and in the hospital so most definitely high yield!

Why is neutropenia dangerous?

Prone to infections, especially gut translocation of bacteria

Definition of neutropenia:

NORMAL: WBC 4400-11000 cells/microL; neutrophils make up 40-70% of that

Neutropenia defined by ANC: WBC (cells/microL) x percent (PMNs + bands) ÷ 100

Breakdown:

Neutropenia: ANC <1500 cells/microL

Mild: ANC ≥1000 and <1500 cells/microL

Moderate: ANC ≥500 and <1000 cells/microL

Severe: ANC <500 cells/microL

Agranulocytosis: ANC <200 cells/microL

Approach to workup: HISTORY IS KEY!

Medications; examples of common culprits-

Chemotherapy

Methimazole

Clozapine

Infections

Any infections due to bone marrow suppression

Toxins

Less common causes:

Congenital

Severe congenital neutropenia:

Diagnosed in childhood; used to be fatal, but now patients living longer because of G-CSF support

10-30% risk of AML in lifetime

Mutations in neutrophil elastase (ELANE) gene or mitochondrial HAX1 gene

Cyclic neutropenia:

Self-limiting neutropenia that occurs every 2-5 weeks

Spectrum of symptoms: none or oral ulcers/mild infections

Constitutional/ethnic neutropenia:

Mild neutropenia (ANC >1000)

No history of infections

More common in people of Mediterranean and African descent

Duffy Antigen Receptor Complex (DARC) gene mutations in patients of African origin

Benign Familial:

Mild neutropenia

Not linked to particular ethnic group

Unclear underlying etiology

Autoimmune

Primary autoimmune neutropenia rare in adults

Typically secondary autoimmune neutropenia

Due to underlying autoimmune disorder

Seen with SLE and can worsen with flare of disease

Typically mild, seldom needs treatment unless ANC <500

Felty syndrome:

Rheumatoid arthritis, splenomegaly, and neutropenia

Neutropenia improves with treatment of RA

Malignancy

Large granular lymphocyte (LGL) leukemia:

Often associated with RA and shares features of Felty syndrome (RA, splenomegaly)

Caused by monoclonal population of large granular lymphocytes

In contrast, in Felty’s: polyclonal or oligoclonal

T-cell LGL is more commonly associated with neutropenia

Requires treatment with methotrexate or cyclophosphamide

Dietary

B12 and folate rarely cause isolated neutropenia

Copper deficiency (gastric bypass): Zinc excess can cause copper deficiencies – ask about denture creams in your history!

Workup:

History:

Prior CBCs

History of recurrent infections (pneumonia, sinusitis, skin/soft tissue, dental caries)

Ethnic background

Family history

Social history

Dietary history

Surgical history (gastric bypass)

Physical exam:

Adenopathy

Splenomegaly

Skin findings suggesting recent ulcers

Aphthous ulcers

example: https://en.wikipedia.org/wiki/Aphthous_stomatitis

Testing:

CBC with differential

CMP – assess liver and renal function

Peripheral smear

HIV, Hepatitis serologies

Special scenarios

ANA – if autoimmune disease expected

RF – if autoimmune disease expected

ESR – if autoimmune disease expected; probably not great for inpatient workup

CRP – if autoimmune disease expected; probably not great for inpatient workup

Flow cytometry for LGL

Bone marrow biopsy – mainly for unexplained neutropenia to rule out neoplastic process, such as leukemia, lymphoma, myeloma; if longstanding, likely negative

Management:

Treat the underlying cause

Autoimmune neutropenia –

When to suspect? Workup is negative, but their counts still continue to worsen

Treatment if they have serious complications

Treat with rituximab

LGL-

Responds to low dose methotrexate or cyclophosphamide

Do you give G-CSF?

For patients with recurrent/severe infections or mucosal erosions

Do not treat based on the number alone

Takes time for the growth factors to work