Ellis Nonmalignant Leukocytosis

Front 1

Leukocytosis definition

Back 1

A total white blood cell count >11 x 103
Where did this number come from?
It is 2 standard deviations above the mean white cell count of people in the US
Recognize that 2.5% of people will have WCCs > 11 and this will be normal

If WBC is elevated, next look at differential

Front 2

Leukocytosis with neutrophilia

Back 2

WBC > 11 K and ANC >7.7 x 103
-ANC (Absolute neutrophil count) = # of PMNs and # bands
-Again, 7.7 x 103 is greater than 2 standard deviations above the mean for ANC

Front 3

Neutrophil locations

Back 3

Bone marrow:
-Mitotic pool
-Maturation pool
-Storage pool
Peripheral blood:
-Circulating pool *
-Marginated pool (stuck to epithelium)
Tissue pool

*CBC measures only circulating pool, sometimes leukocytosis and neutrophilia may be due to redistribution of neutrophils from one pool to another.

Front 4

Neutrophil mobilization

Back 4

To enter circulation from bone
marrow, neutrophils must deform and squeeze in between endothelial
cells into circulation
Endotoxin causes the gap between endothelial cells to widen, allowing for better egress
Neutrophil mobilization from the bone marrow storage pool to the circulating pool can result in 2-3 times the normal neutrophil count in a matter of a few hours
More than half of the neutrophils in the circulation are attached to the vascular endothelium (marginated)
These neutrophils can be
demarginated within minutes,
if needed (epinepherine and steroids can stimulate this)

Front 5

Causes of leukocytosis and neutrophilia

Back 5

Infection
Stress
-Physical
-emotional
Smoking
Pregnancy
Post-exercise setting
Myocardial infarction
Generalized marrow stimulation (hemolysis)
Administration of recombinant growth factors
-GCSF (Granulocyte colony stimulating factor)
--Filgrastim, Neupogen
--Peg-filgrastim, Neulasta
-GMCSF (Granulocyte monocyte colony stimulating factor)
--Sargramostim (Leukine)

Front 6

Leukocytosis and bandemia

Back 6

WBC > 11K and absolute band count > 0.7 x 103
“Left shift”
Seen in acute bacterial infections
Should not see more immature cells on differential

Front 7

Leukocytosis and lymphocytosis

Back 7

ALC (Absolute lymphocyte count) > 4.8 x 103
Usual causes are responses to viral infection
Can have normal lymphocyte morphology or reactive lymphocyte morphology

Front 8

Causes of leukocytosis and lymphocytosis

Back 8

Viral
Non-viral
-Bordetella pertussis (whooping cough)
-Bartonella henselae (cat scratch disease)
-Toxoplasmosis
-Babesiosis
Non-infectious
-Hypersensitivity reactions
-Stress

Front 9

Leukocytosis and monocytosis

Back 9

WCC > 11 x 103 and absolute monocyte count > 0.8 x 103
Can also be seen in acute bacterial infection
Can be seen in tuberculosis
Can be seen after GM-CSF administration

Front 10

Leukocytosis and eosinophilia

Back 10

WCC > 11 x 103 and absolute eosinophil count (AEC) > 0.45 x 103
Primary eosinophilia
-malignancy
Secondary eosinophilia
-Infectious
--Parasites (Strongyloides, hookworm, Toxocara canis)
--Aspergillus
-Non-infectious
--Allergic disorders (atopic dermatitis, asthma, rhinitis syndromes)
--Medications (many)
--Toxins
--Autoimmune diseases
--Endocrine disorders
Idiopathic eosinophilia

Front 11

Leukocytosis and basophilia

Back 11

WCC > 11 x 103 and ABC (Absolute Basophil Count) > 0.2 x 103
Causes:
-Hypersensitivity reactions
-Ulcerative colitis
-Rheumatoid arthritis
-Hypothyroidism
-Exogenous estrogen supplementation
-Infections:
--Viral
--Tuberculosis
--Helminths

Front 12

Leukopenia and neutropenia

Back 12

ANC < 1.5 x 103
Normal variant
-African-Americans
-Nonsmokers
Pseudo-neutropenia
-Increased percentage of neutrophils marginated along endothelial vessel walls
-Still able to demarginate when needed
-No history of difficulty fighting infection

Front 13

Leukopenia and neutropenia caused by infection

Back 13

Infection
-Particularly viral infections, which cause a transient neutropenia
-Mononucleosis, hepatitis B, and HIV can cause more protracted courses of neutropenia
-Mechanisms include:
--Marrow suppression
--Upregulation of adhesion and migration due to complement and cytokine release

Front 14

Leukopenia and neutropenia caused by medication

Back 14

Medication-induced
-Over 100 drugs implicated
-Mechanisms:
--Immune-mediated: metabolite of drug binds to neutrophil (or precursor) membrane and antibodies or T cells destroy the cell
--Direct toxicity: neutrophils (or precursors) metabolize drug to toxic compound that results in cell death

Front 15

Leukopenia and neutropenia caused by immune mediated processes

Back 15

Anti-neutrophil antibodies (or antibodies to neutrophil precursors)
Can be seen with other immune-mediated disorders
-Autoimmune mediated hemolytic anemia
-Immune-mediated thrombocytopenia
-Autoimmune disorders

Front 16

Leukopenia and neutropenia caused by congenital reasons

Back 16

Congenital
Cyclic neutropenia:
-Autosomal dominant
-Marked neutropenia every 21 days, nadir will last 3 to 7 days
-Patients develop recurrent severe infections
Kostmann syndrome (severe congenital neutropenia)
-Present at birth
-ANC < 0.2
-Predisposed to leukemia and other blood dyscrasias

Front 17

Leukopenia and lymphopenia

Back 17

ALC < 1.5 x 103
Causes:
-Decreased production
--Immunodeficiency diseases
---AIDS
---Aplastic anemia
Increased destruction
-Steroids/other immunosuppressive agents
-Chemotherapy
-Radiation
Congenital disorders