Labs

Labs (1 of 40 slides)

Labs (2 of 40 slides)

Let’s begin with the patient’s CBC:

WBC (10⁹/L)	Hb (g/dL)	MCV (fL)	PLT (10⁹/L)
3.8	14.5	80	211

What’s what: WBC, white blood cell count; Hb, hemoglobin; MCV, mean cell volume; MCHC, mean cellular hemoglobin concentration; RDW-SD, red cell distribution width-standard deviation; platelets, PLT; Normal values: WBC 5-10 x 10⁹/L, RBC 4-6 x 10¹²/L, Hb 12-16 g/dL, Hct 35-47%, MCV 80-100 fL, MCHC 32-36 g/dL, RDW-SD < 45%, platelets (PLT) 150-450 x 10⁹/L

The CBC reveals leukopenia (defined by white cell count < 4.5 x 10⁹/L) and a low normal MCV.

Labs (2 of 40 slides)

Let’s begin with the patient’s CBC:

WBC (10⁹/L)	Hb (g/dL)	MCV (fL)	PLT (10⁹/L)
3.8	14.5	80	211

The CBC reveals leukopenia (defined by white cell count < 4.5 x 10⁹/L) and a low normal MCV.

Whenever the WBC count is abnormal, we should order a white cell differential. This showed:

Absolute neutrophil count 0.91 x 10⁹/L, absolute lymphocyte count 2.46, absolute monocyte count 0.36, absolute basophil count 0.02, absolute eosinophil count 0.03.

In summary, the CBC and differential shows:

Click for Answer

Leukopenia from neutropenia

A previous CBC from 2 years ago showed:

WBC (10⁹/L)	Hb (g/dL)	MCV (fL)	PLT (10⁹/L)
4.5	14.5	80	227

The previous WBC is not particularly low, so this must be an acquired neutropenia, right?

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Wrong! The differential showed ANC 1.15 x 109/L, which meets the definition of neutropenia. A normal CBC can mask an abnormality in the number of different white cell subsets.

The MCV is on the low side. What are possible explanations?

Thalassemia minor

Iron deficiency

Hb C trait

Pernicious anemia

Hypothyroidism

What is the most likely diagnosis for the patient’s neutropenia

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Ethnic or benign neutropenia; diagnosed by repeated low measurements of absolute neutrophil counts less than 1500 cells/ml (usually 1000 cells/ml or below) for several months without identifiable causes of neutropenia and no history of infections. BEN is largely a diagnosis of exclusion. At least three blood samples showing neutropenia at intervals of at least two weeks and with no other identifiable causes.

Remind me what the definition of neutropenia is again?

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Neutropenia is defined as an abnormally low number of circulating neutrophils in the peripheral blood, with an absolute neutrophil count (ANC) ≤ 1.5 × 109/L in adults and children aged > 12 months; ANC < 2 × 109/L in infants aged 2-12 months; < 2.5 × 109/L in neonates and infants aged < 2 months

What is the prevalence of BEN in persons of African descent?

25–50% persons of African descent

4% persons of African descent

70-75% persons of African descent

What other ethnicities have an increased incidence of BEN?

Middle Eastern descent

West Indian descent

Irish descent

African descent

Yemenite Jews

The peripheral smear is unremarkable. What other labs would you like to order?

None, simply wait and watch

ANA and dsDNA

Haptoglobin

Once the diagnosis is confirmed, this entity does not require monitoring or hospital admission. This type of neutropenia does not require any treatment, including no antimicrobial prophylaxis or G-CSF. These individuals are healthy subjects, and are expected to have a lower ANC than current reference ranges without concern for increased infections. in asymptomatic persons of African descent with mild neutropenia, extensive work-up is not necessary

perform serial CBC panels over a period of days or weeks to establish trend in neutrophil count and chronicity

ideally confirm neutropenia with 3 CBCs per week over a 6-week period in order to account for physiological fluctuations

outpatient investigations of ANC between 1 × 10⁹/L and 1.5 × 10⁹/L in individuals of certain ethnicities (African, Middle Eastern, and Caribbean) not recommended outside setting of recurrent infections, fever, recurrent or severe oral ulcers, lymphadenopathy, splenomegaly or other cytopenia(s)
outpatient investigations of ANC between 0.5 × 10⁹/L and 1 × 10⁹/L recommended in individuals of certain ethnicities to rule out secondary causes of neutropenia
monitoring ANC after diagnosis of benign ethnic neutropenia is not necessary

Other labs to consider according to cause of neutropenia:

Infection

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obtain serology and cultures for

viruses (EBCV, CMV, HIV, influenza) which may cause transient neutropenia
mycobacterial, rickettsial, protozoan, other bacterial infection

Autoimmune disease

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rheumatoid factor as screening for RA
antinuclear antibodies (ANA) as initial screening test for SLE
erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for detecting underlying inflammation
measure quantitative immunoglobulin (Ig)G, IgA, and IgM
antineutrophil antibodies
- more useful in pediatric age group
- use in diagnosing adult with autoimmune neutropenia is controversial
- high rate of false-positives and false-negatives

Evaluation of suspected congenital neutropenia

establish chronic neutropenia by evaluating complete blood count (CBC) with differential over a period of days or weeks to confirm trend of neutropenia lasting ≥ 3 months, or by documenting low counts in past

assess severity of neutropenia and presence of recurrent or severe infections

if using genetic sequencing to confirm diagnosis of severe congenital neutropenia (SCN), consider sequencing ELANE first (mutations in ELANE are most common) unless family history, physical examination, or laboratory testing results suggest other diagnosis

if SCN is suspected, assess for ELANE and HAX1 gene mutations
if cyclic neutropenia is suspected¹
- perform serial complete blood counts with differential ≥ twice weekly for a minimum of 4-6 weeks to establish cyclic pattern
- assess for ELANE gene mutation