Benign White Cell Disorders:
Now we will look at increases in white cell number above
the normal range for age and sex. For adults this is >
11.0 x109/L leukocytes. An increase in the WBC
count (leukocytosis) is a typical response to noxious
stimuli and is usually part of an inflammatory reaction.
A leukocytosis is frequently accompanied by cytologic
abnormalities, such as toxic granulation or Dohle bodies
(discussed later in this section). Although all or
individual types of leukocytes (neutrophils, lymphocytes,
etc.) may be increased in number, we will concentrate on the
most common: 1) neutrophilia (granulocytosis) and 2)
Neutrophilia may be due to a number of acute and
chronic causes: infection, inflammation, necrosis, physical
agents, emotional stimuli, drugs, toxins, neoplasia,
metabolic, hormonal, and endocrine disturbances, and
In response to inflammation or other stimuli, neutrophils
move from the marginating or storage pool into the
circulating peripheral blood. Next bone marow reserves are
shifted into the peripheral blood and finally marrow
production is increased.
Immature neutrophils (bands, metamyelocytes, myelocytes,
and occasionally promyelocytes) are released into the
peripheral blood. This premature release of not yet
fully mature neutrophils is called a myeloid "left
Normal mature neutrophils contain small amounts of
leukocyte alkaline phosphatase (LAP) in primary granules.
The peripheral blood LAP is elevated during leukocytosis
because of the "left shift".
Minor causes of leukocytosis include:
Pseudoneutrophilia may result in response to acute
stress (exercise, epinephrine,anesthesia, etc.) There is no
increase in the total number of neutrophils, only a shift
from the marginal storage pool to the circulating blood.
Asplenia can result in a moderate leukocytosis as
the normal spleen holds a large part of the marginating pool
Corticosteroids may stimulate the release of
neutrophils from the marrow and slow or prevent the
egress of neutrophils from the circulation.
Three conditions related to leukocytosis are leukostasis,
and leukemoid and leukoerythroblastic reactions.
Leukostasis results from sludging of high numbers
of leukocytes in small vessels, particularly the brain,
lungs, and kidneys. Death may occur due to impaired blood
flow or enormous metabolic requirements of large numbers of
leukocytes. Leukostasis is most common with myeloid leukemia
(blast counts >50.0 x109/L) but are rare in
chronic lymphocytic leukemia (CLL) with any white count.
This may be due to the large size of the myeloid blasts
compared to CLL cells or may relate to different expression
of intercellular adhesion molecules.
Leukemoid reactions are characterized by blasts,
promyelocytes, myelocytes, and metamyelocytes in the
Leukemoid reactions may be secondary to benign or
The WBC count is often in a range of 50.0-100.0 x10
A leukoerythroblastic reaction is similar to a
leukomoid reaction with the addition of nucleated red blood
cells. A leukoerythroblastic picture indicates severe
disruption of the marrow and is common in myelofibrosis
(primary or secondary).
Leukoerythroblastic reactions suggest possible
extramedullary hemtopoiesis and is often secondary to
In infants a leukoerythroblastic reaction suggests severe
hemolytic anemia, such as erythroblastosis fetalis (shown
Another disease, osteopetrosis is a rare childhood
disorder of bone in which abnormal osteoclasts are unable to
resorb bone. Thus bone unable to be remodelled, replaces
hematopoietic marrow space, leading to extramedullary
hematopoiesis and spillage of hematopoietic elements into
the peripheral blood.
In addition to neutrophilia one may encounter specific
increases in the number of lymphocytes, eosinophils,
basophils, and monocytes in the peripheral blood.
Of these, most common is lymphocytosis (
lymphocytes > 4.0 x109/L in adults and >
9.0 x109/L in children ).
One must always consider the absolute lymphocyte
count to determine if a lymphocytosis is present.
Lymphocytoses occur most frequently during viral
infections and only rarely in bacterial infection except
Pertussis or whooping cough is frequently
accompanied by a lymphocytosis ( usually 20.0-30.0
x109/L, but may exceed 50.0 x109/L )
of small mature appearing lymphocytes.
Toxoplasmosis may cause an lymphocytosis similar
to infectious mononucleosis with atypical lymphocytes,
fever, and lymphadenopathy.
The chronic infections brucellosis and
syphilis may occassionally cause an atypical
Infectious mononucleosis - The disease is
generally self limited and is caused by an Epstein-Barr
virus infection of B lymphocytes. During the second week of
illness, a proliferation of activated cyotoxic/suppressor T
It is these CD8 positive T cytotoxic/suppressor cells
that we see in the PB and that kill the infected B cells.
The atypical lymphocytes are large and reactive with
abundant basophilic cytoplasm. Some may appear almost
blast-like. These changes are not unique to IM, but can be
seen in other viral infections.
Infectious mononucleosis is most common in adolescents
and young adults.Patients present with fever, sore throat,
and lymphadenopathy (often cervical). Splenomegaly is
common. CMV occassionally causes a lymphocytosis with
symptoms similar to IM and may follow blood
Other viral causes of lymphocytosis include infectious
lymphocytosis and HTLV-1 related transient
Infectious lymphocytosis is characterized by a
lymphocytosis of small lymphocytes, generally 20.0-50.0
x109/L, but occasionlly over 100.0
x109/L. This is mainly a disease of children and
is benign. It may be related to coxsackievirus A or B6,
echovirus, and adenovirus 12. There is almost never
splenomegaly or lymphadenopathy.
HTLV-1 may produce a transient lymphocytosis
(usually < 20.0 x109/L) with fever,rash, and
little lymphadenopathy. Most patients recover; however, some
develop adult T cell leukemia.
Other forms of leukocytosis:
Monocytosis (monocytes > 1.0 x109/L
in adults occurs in a number of disorders, most frequently
in the recovery phase of infection, but may be seen in a
variety of neoplastic lesions especially myeloproliferative
disorders. Monocytosis may result from viral, fungal,
rickettsial, and protozoal infections.
Phagocytosis of erythrocytes, leukocytes, and platelets
by monocytes and histiocytes is seen in the
"hemophagocytic syndrome" which is associated with
viral or bacterial infections and T cell malignant
Eosinophilia ( > 0.35 X 109/L ) is
associated with many forms of immunologic damage and can,
interestingly, inactivate IgE mediated reactions (immediate
- allergic disorders -asthma, seasonal rhinitis,
eczema, atopic dermatosis, pemphigus and dermatitis
- parasitic infections - trichinosis, tapeworm,
roundworm, schistosomiasis.MBP (major basic protein)
released from the eosinophilic granules coats the
Schistosoma organism prior to antibody-complement
- other infections - scarlet fever, TB, leprosy
- Loeffler's syndrome
- PIE (pulmonary infiltration with eosinophilia)
- tropical pulmonary eosinophilia
- drug induced - sulfonamides, PCN, digitalis,
- neoplastic - CML, tumors, (particularly involving
serous linings, occasionally Hodgkin's disease).
When large numbers of eosinophils are present the
crytalloid material may form Charot-Leyden crystals.
Basophilia ( > 0.2 X 109/L ) is seen in
allerigic reactions and is common in chronic myelocytic
leukemia. Increased basophils are associated with
polycythemia vera and extramedullary hematopoiesis.
Basophilia is also reported in hypothyroidism.