Quantitative Disorders

WBC Non-Neoplastic Disorders

Some terms we need to review for this
lecture…
Term Definition Example
Absolute Actual count of a specific type of If Total WBC Count is 6 x 109/L
WBC and the differential count shows
Relative Number of specific type of WBC in 90%relative count of neutrophils,
relation to total WBC count absolute neutrophil count is 5.4 x
109/L
-philia Increased cell count Neutrophilia, Eosinophilia, Basophilia
-cytosis Increased number of cells Leukocytosis, Lymphocytosis,
Monocytosis
-penia Decreased number of cells Leukopenia, Neutropenia
 WBC Differential Count
Reference Range (Adults)
Reference: Rodak’s 6th Ed.

W B C C o u n t 3.6-10.6 x 109/L
Relative Count (%) Absolute Count (x 109/L)

Neutrophil 50-70 1.7-7.5

Lymphocytes 18-42 1.0-3.2
Monocytes 2-11 0.1-1.3
Eosinophils 1-3 0-0.3
Basophils 0-2 0-0.2
Classification
of WBC
Disorders
Total WBC count is >11 x 109/L Total WBC count is <4 x 109/L
NEUTROPHILS

Mitotic
Compartment
Circulating
Bone Marrow
Compartment
Maturation
Blood flow
Compartment
Marginating
Compartment
NEUTROPHILS

Mitotic
Compartment
Circulating
Bone Marrow
Compartment
Maturation
Blood flow
Compartment
Marginating
Compartment
NEUTROPHILIA
➥ Leukocytosis of 15-30 x 109/L
➥ >70% Neutrophils
➥ Adults >7.0 x 109/L
➥ Children >8.5 x 109/L Causes:
 Catecholamine-induced
shift from migrating
pool to circulating pool
 Increase in bone
marrow production of
neutrophils
Often accompanied by “left-shift”  Transfer from bone
marrow storage pool to
circulating pool
NEUTROPHILIA

NOTE:
True neutrophilia is usually
related to infections
NEUTROPHILIA
Leukemoid Reaction
Reactive Neutrophilia

Persistence of neutrophilia

Increase neutrophil
Differentiation:
precursors in the circulation
 Cytogenetic Testing
 Cytochemical Testing
➟ Leukocyte Alkaline Phosphatase (LAP)
WBC >50 x 109/L ✩ Leukemoid Reaction = ↑ LAP Score
✩ Chronic Myeloid Leukemia = ↓ LAP Score
↑ Immature neutrophils
 A

NEUTROPHILIA

Leukoerythroblastic Reaction
1. Space-occupying lesion in the BM
2. Primary Myelofibrosis
NEUTROPHILIA work-up

Complete history and physical examination

Assess CBC

ESR

Bone marrow examination

NEUTROPENIA
✦ Agranulocytosis = Neutrophils <0.5 x 109/L

Cyclic Neutropenia
➟ Occurrence of neutropenia starting
infancy with periodic alteration of
neutrophil count from normal to
neutropenic levels followed by a
recovery phase

chronic BeNign NeutroPEnia

➟ reduced BM myeloid reserve pool
➟ reduced mitotic pool

CONGEnITaL Neutropenia (Myelokathexis

type)
➟ Inability to release mature
granulocytes
 NEUTROPENIA
✦ Agranulocytosis = Neutrophils <0.5 x 109/L

Immune Neutropenia
✢ Neonatal Alloimmune
Neutropenia
➟
( )

✢ Autoimmune Neutropenia
➟
➟ -
NEUTROPENIA
✦ Agranulocytosis = Neutrophils <0.5 x 109/L

DRUGS AS CAUSE OF NEUTROPENIA

1. Chemotherapeutic agents
2. Anti-inflammatory drugs = neutropenia develops as an
idiosyncratic reaction
3. Anti-thyroid = destruction of mature neutrophils,
usu. by immunologic mechanism
4. Anti-bacterial = some causes aplasia in the bone
marrow (e.g. chloramphenicol)
5. Phenothiazines = direct toxic effects on granulocyte
precursors
EOSINOPHILS
EOSINOPHILS
 BM proliferation rate
and release into the
blood

 Movement from blood

into the extravascular
tissues

 Cell survival and

destruction after
eosinophils have moved
from the blood to the
tissues
EOSINOPHILIA
Eosinophils >0.4 x 109/L

Parasitic infection

Allergic reaction Charcot-Leyden Crystals

Large orange-red hexagonal or diamond-shaped cyrstals within the cytoplasm of

eosinophils , tissues or body fluids infiltrated by eosinophils
 EOSINOPHILIA
✢ Hyperimmunoglobulin E
Syndrome (Job’s Syndrome)
➟Mutation in STAT3 gene
➟Abnormal chemotactic ability of
neutrophils
➟Triad:
➟Eosinophilia
➟Increased serum IgE (>2000 IU/mL
➟Recurrent skin and pulmonary
infections
EOSINOPENIA

STRESS ↑ ↑ ↑ glucocorticoids

Eosinphil chemotaxis
Eosinophil adherence
BASOPHILS
 Factors affecting:
✩ Time of day
✩ Age

BASOPHILIA
✩ Physical activity
✩ Hormones
✦ ACTH
✦ Progesterone
✦ Thyroid Hormones
MONOCYTES
Inflammation

Infection

Hypersensitivity reactions

Immunologic conditions
MONOCYTOSIS
Neonates = >3.5 x 109/L
Adults = >1.0 x 109/L
MONOCYTOPENIA
Monocytes <2.2 x 109/L

 Usually associated with other lineage cytopenia

 Steroid therapy

 Certain viral infection (e.g. EBV)

LYMPHOCYTES
Constitute 20-40% of circulating WBCs in adults
LYMPHOCYTOSIS
Children = >10.0 x 109/L
Adults = >5.0 x 109/L
LYMPHOCYTOSIS
Usually accompanied with changes in morphology of lymphocytes
Children = >10.0 x 109/L
Adults = >5.0 x 109/L
✢ Infectious Mononucleosis
➟Infection caused by Epstein-Barr Virus
➟Appearance of lymphocyte variant of T origin.
LYMPHOCYTOSIS
Usually accompanied with changes in morphology of lymphocytes
Children = >10.0 x 109/L
Adults = >5.0 x 109/L
✢ Infectious Mononucleosis
➟Infection caused by Epstein-Barr Virus
➟Appearance of lymphocyte variant of T origin.
➟Associated with production of heterophile
antibody
LYMPHOCYTOSIS
Usually accompanied with changes in morphology of lymphocytes
Children = >10.0 x 109/L
Adults = >5.0 x 109/L
✢ Cytomegalovirus
➟Considered as one of the most important causes
of congenital viral infection in the US
➟Slight lymphocytosis, 20% variant lymphocytes
➟Cells with “Owl-eye” appearance
LYMPHOCYTOSIS
Usually accompanied with changes in morphology of lymphocytes
Children = >10.0 x 109/L
Adults = >5.0 x 109/L
✢ Toxoplasmosis
➟Caused by Toxoplasma gondii
➟Disease may resemble infectious mononucleosis
➟Chills, fever, headache, lymphadenopathy
➟Presence of variant lymphocytes
 LYMPHOCYTOSIS
Usually accompanied with changes in morphology of lymphocytes
Children = >10.0 x 109/L
Adults = >5.0 x 109/L

✢ Reactive Lymphocytosis
➟relatively fragile cells, and as a result can be squeezed out of
shape by surrounding cells, giving them a scalloped appearance
instead of a smooth cytoplasmic edge. The nucleus of the reactive
lymphocyte is larger than that of the small lymphocyte and is more
irregular in shape.
 LYMPHOCYTOSIS
Usually accompanied with changes in morphology of lymphocytes
Children = >10.0 x 109/L
Adults = >5.0 x 109/L

✢ Reactive Lymphocytosis
LYMPHOCYTOSIS
Usually accompanied with changes in morphology of lymphocytes
Children = >10.0 x 109/L
Adults = >5.0 x 109/L

✢Bordetella pertussis
➟Causative agent of whooping cough
➟Leukocytosis 100 x 109/L
➟Lymphocytosis 50 x 109/
LYMPHOCYTOPENIA
Adults <1.0 x 109/L
Children <2.0 x 109/L

 In response to stress and corticosteroids

 Pathologic causes:
➟ Decreased production
➟ Mechanical loss
➟ Increased destruction
➟ Functional abnormalities
LYMPHOCYTES
Quantitative Disorders

WBC Non-Neoplastic Disorders