Chapter 13 – D/O WBC: Leukopenia

Question 1

Disorders of white blood cells can be classified into two broad categories

Answer 1

• proliferative disorders, in which there is an expansion of leukocytes,
• and leukopenias, which are defined as a deficiency of leukocytes.

Question 2

What are leukopenias?

Answer 2

leukopenias, which are defined as
a deficiency of leukocytes.

Question 3

The proliferation of white cells can be either what?

Answer 3

Proliferations of white cells can be reactive or neoplastic

Question 4

What is the more common kind of proliferation of WBC and why?

Answer 4

Since the
major function of leukocytes is host defense, reactive proliferation in response to an underlying
primary, often microbial, disease is fairly common.

Neoplastic disorders, though less frequent,
are much more important clinically.

Question 5

What is leukopenia?

Answer 5

The number of circulating white cells may be markedly decreased in a variety of disorders.

An
abnormally low white cell count (leukopenia) usually results from reduced numbers of
neutrophils (neutropenia, granulocytopenia).

Question 6

Where is lymphopenia most commonly observed?

Answer 6

Lymphopenia is less common; in addition to
congenital immunodeficiency diseases (see Chapter 6 ), it is most commonly observed in
advanced human immunodeficiency virus (HIV) infection, following therapy with glucocorticoids
or cytotoxic drugs,autoimmune disorders,malnutrition, and certain acute viral infections.

In the latter setting lymphopenia actually stems from lymphocyte activation rather than a true
decrease in the number of lymphocytes in the body.

You will recall that acute viral infections
induce production of type I interferons, which activate T lymphocytes and change the
expression of a number of surface proteins that regulate T cell migration. These changes result
in the sequestration of activated T cells in lymph nodes and increased adherence to endothelial
cells, both of which contribute to lymphopenia.

Question 7

What is Granulocytopenia?

Answer 7

Granulocytopenia is more common and is often
associated with significantly decreased granulocyte function, and thus merits further discussion.

Question 8

What is neutropenia?

Answer 8

Neutropenia, a reduction in the number of neutrophils in the blood, occurs in a wide variety of
circumstances.

Question 9

What is Agranulocytosis?

Answer 9

Agranulocytosis, a clinically significant reduction in neutrophils, has the serious
consequence of making individuals susceptible to bacterial and fungal infections

Question 10

A reduction in circulating granulocytes occurs if there is:

Answer 10

A reduction in circulating granulocytes occurs if there is:

• (1) inadequate or ineffective granulopoiesis, or
• (2) accelerated removal of neutrophils from the blood.

Question 11

Inadequate or
ineffective granulopoiesis is observed in the setting of

Answer 11

• Suppression of hematopoietic stem cells, as occurs in aplastic anemia (see Chapter 14 ) and a variety of infiltrative marrow disorders (tumors, granulomatous disease, etc.); in these conditions granulocytopenia is accompanied by anemia and thrombocytopenia
• Suppression of committed granulocytic precursors by exposure to certain drugs
(discussed below)
• Disease states associated with ineffective hematopoiesis, such as megaloblastic
anemias ( Chapter 14 ) and myelodysplastic syndromes, where defective precursors die in the marrow
• Rare congenital conditions (such as Kostmann syndrome) in which inherited defects in
specific genes impair granulocytic differentiation

Question 12

Accelerated removal or destruction of neutrophils occurs with

Answer 12

• Immunologically mediated injury to neutrophils, which can be idiopathic, associated with a well-defined immunological disorder (e.g., systemic lupus erythematosus), or caused by exposure to drugs
• Splenomegaly, in which splenic sequestration of neutrophils leads to excessive destruction, usually associated with increased destruction of red cells and platelets as well
• Increased peripheral utilization , which can occur in overwhelming bacterial, fungal, or rickettsial infections

Question 13

What is the most common cause of agranulocytosis?

Answer 13

drug toxicity .

Question 14

How can drugs cause agranulocytosis?

Answer 14

Certain drugs, such as alkylating
agents and antimetabolitesused in cancer treatment, produce agranulocytosis in a predictable,
dose-related fashion.

Because such drugs cause a generalized suppression of the bone marrow, production of red cells and platelets is also affected.

Agranulocytosis can also occur as
an idiosyncratic reaction to a large variety of agents. The roster of implicated drugs includes

Question 15

What are the roster of implicated drugs that cause agranulocytosis ?

Answer 15

• aminopyrine, ( antipyretic)
• chloramphenicol ( antibacterial)
• sulfonamides (antibacterial)
• chlorpromazine (antipsychotic)
• thiouracil, ( antithyroid)
• phenylbutazone ( NSAID)

PACCTS

a

• *c**at
• *s**ells
• *c**ocaine
• *t**o
• *p**easants

Answer 16

The neutropenia induced by chlorpromazine and related phenothiazines results from a toxic
effect on granulocytic precursors in the bone marrow

Question 17

How does following
administration of aminopyrine, thiouracil, and certain sulfonamides cause agranulocytosis?

Answer 17

In contrast, agranulocytosis following
administration of aminopyrine, thiouracil, and certain sulfonamides probably stems from
antibody-mediated destruction of mature neutrophils through mechanisms similar to those
involved in drug-induced immunohemolytic anemias

Question 18

In some patients with acquired idiopathic neutropenia what are detected?

Answer 18

In some patients with acquired idiopathic neutropenia, autoantibodies directed against
neutrophil-specific antigens are detected.

Question 19

What is the mechanism of neutropenia in LGL leukemia?

Answer 19

Severe neutropenia can also occur in association
with monoclonal proliferations of large granular lymphocytes (so-called LGL leukemia). [3]

The mechanism of this neutropenia is not clear; suppression of marrow granulocytic progenitors by
products of the neoplastic cell (usually a CD8+ cytotoxic T cell) is considered most likely.

Question 20

With excessive destruction of neutrophils in the periphery, what is the appearance of marrow?

Answer 20

The alterations in the bone marrow vary with cause.

With excessive
destruction of neutrophils in the periphery, the marrow is usually hypercellular due to a
compensatory increase in granulocytic precursors.

Hypercellularity is also the rule with
neutropenias caused by ineffective granulopoiesis, as occurs in megaloblastic anemias and
myelodysplastic syndromes.

Agranulocytosis caused by agents that suppress or destroy granulocytic precursors is understandably associated with marrow hypocellularity.

Question 21

What is the rule of neutropenias caused by inffective granulopoiesis?

Answer 21

Hypercellularity is also the rule with
neutropenias caused by ineffective granulopoiesis, as occurs in megaloblastic anemias and
myelodysplastic syndromes.

Question 22

What is the appearance of marrow when there is agranulocytosis associated agents that suppress or destroy granulocytic precursors?

Answer 22

marrow hypocellularity.

Question 23

What are the common consequence of agranulocytosis?

Answer 23

Infections

Question 24

What is the characteristic of infections as a consequence of agranulocytosis?

Answer 24

• Ulcerating necrotizing lesions of the gingiva, floor of the mouth, buccal mucosa, pharynx, or elsewhere in the oral cavity (agranulocytic angina) are quite characteristic.
  
  • These are typically deep, undermined,
  • and covered by gray to green-black necrotic membranes from which numerous bacteria or fungi can be isolated.
• Less frequently, similar ulcerative lesions occur in the skin, vagina, anus, or gastrointestinal tract.
• Severe life-threatening invasive bacterial or fungal infections may occur in the lungs, urinary tract, and kidneys.

Question 25

The neutropenic patient is at particularly
high risk for deep fungal infections caused by ___________

Answer 25

Candida and Aspergillus

Sites of infection
often show a massive growth of organisms with little leukocytic response. In the most
dramatic instances, bacteria grow in colonies (botryomycosis) resembling those seen on
agar plates.

Question 26

What are the s/sx of neutropenia related to infection ?

Answer 26

The symptoms and signs of neutropenia are related to infection, and include malaise, chills,
and fever,oftenfollowed by marked weaknessandfatigability.

Question 27

With agranulocytosis, infections
are often overwhelming and may cause death within hours to days..

T or F

Answer 27

True

Question 28

What count is when serious infections occur?

Answer 28

Serious infections are most likely when the neutrophil count falls below 500 per mm3 .

Because
infections are often fulminant, broad-spectrum antibiotics must be given expeditiously whenever
signs or symptoms appear.

In some instances, such as following myelosuppressive
chemotherapy, neutropenia is treated with G-CSF, a growth factor that stimulates the production
of granulocytes from marrow precursors.