Chapter 27
Alterations of Leukocyte, Lymphoid,
and Hemostatic Function
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Alterations of Leukocyte Function



Deficiencies in the quality and quantity of
leukocytes (leukopenia)
Increased numbers of leukocytes
(leukocytosis)
Many hematologic disorders are
malignancies

Many nonhematologic malignancies metastasize
to bone marrow, affecting leukocyte production
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Alterations of Leukocyte Function

Quantitative disorders




Increases or decreases in cell numbers
Bone marrow disorders or premature destruction
of cells
Response to infectious microorganism invasion
Qualitative disorders

Disruption of cellular function
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Quantitative Alterations
of Leukocytes

Leukocytosis



Counts higher than normal
Leukocytosis is a normal protective physiologic
response to stressors
Leukopenia

Counts lower than normal
 Leukopenia is always abnormal
 Low WBC count predisposes to infections
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Granulocytosis (Neutrophilia)



Evident in first stages of infection/inflammation
If need for neutrophils increases beyond the
supply, immature neutrophils (banded
neutrophils) released into the blood
Premature release detected in manual WBC
differential and is termed a shift to the left


Leukemoid reaction
When the population returns to normal, it is
termed a shift to the right
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Neutropenia

Reduction in circulating neutrophils

Primary
• Congenital


Cyclic neutropenia and neutropenia with congenital
immunodeficiency diseases
Multiple syndromes
• Acquired


Multiple conditions (hypoplastic anemia, aplastic anemia,
leukemias, lymphomas [Hodgkin, non-Hodgkin];
myelodysplastic syndrome)
Secondary
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Neutropenia

Causes




Prolonged severe infection
Decreased production
Reduced survival
Abnormal neutrophil distribution and sequestration
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Granulocytopenia
(Agranulocytosis)

Causes





Interference with hematopoiesis
Immune mechanisms
Chemotherapy destruction
Ionizing radiation
Sepsis caused by agranulocytosis often
results in death within 3 to 6 days
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Eosinophilia



Hypersensitivity reactions trigger the
release of eosinophilic chemotactic factor of
anaphylaxis from mast cells
Increased in allergic disorders
Increased in parasitic invasions
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Eosinopenia



Decrease in circulation numbers of
eosinophils
Usually caused by migration of cells to
inflammatory sites
Other causes

Surgery, shock, trauma, burns, or mental
distress
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Basophils


Basophils account for only up to 1% of the
circulating WBCs
Basophilia


Response to inflammation and hypersensitivity
reactions
Basopenia

Occurs in acute infections, hyperthyroidism, and
long-term steroid therapy
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Monocytes

Monocytosis

Poor correlation with disease
 Usually occurs with neutropenia in later stages of
infections
 Monocytes are needed to phagocytize organisms and
debris

Monocytopenia

Very little known about this condition
• Prednisone treatments
• Hairy cell leukemia
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Lymphocytes

Lymphocytosis


Acute viral infections
• Epstein-Barr virus
Lymphocytopenia

Immune deficiencies, drug destruction, viral
destruction
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Infectious Mononucleosis (IM)


Acute, self-limiting infection of B
lymphocytes transmitted by saliva through
personal contact
Commonly caused by the Epstein-Barr virus
(EBV)—85%

B cells have an EBV receptor site
 Others viral agents resembling IM
• Cytomegalovirus (CMV), hepatitis, influenza, HIV
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Infectious Mononucleosis


Symptoms: fever, sore throat, swollen cervical
lymph nodes, increased lymphocyte count, and
atypical (activated) lymphocytes; may affect
multiple systems
Serious complications are infrequent (<5%)



Lab values: >50% lymphocytes and at least
10% atypical lymphocytes
Diagnostic test


Splenic rupture is the most common cause of death
Monospot qualitative test for heterophilic antibodies
Treatment: symptomatic
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Leukemias


Malignant disorder of the blood and bloodforming organs
Uncontrolled proliferation of malignant
leukocytes


Overcrowding of bone marrow
Decreased production and function of normal
hematopoietic cells
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Leukemias

Acute leukemia



Presence of undifferentiated or immature cells,
usually blast cells
Rapid onset with short survival
Chronic leukemia


Predominant cell is mature but does not function
normally
Slow progression
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Leukemias

Acute lymphocytic leukemia (ALL)


Least common overall but most common childhood
leukemia (80%)
Acute myelogenous leukemia (AML)

Most common adult leukemia (mean age, 67)
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Leukemias

Chronic myelogenous leukemia (CML)


Usually diagnosed in adults
Chronic lymphocytic leukemia (CLL)

Common in adults (70% asymptomatic at diagnosis)
• Lymphadenopathy
• Suppression of humoral immunity
• Increased infection with encapsulated bacteria
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Leukemias

Signs and symptoms of leukemias


Anemia, bleeding purpura, petechiae, ecchymosis,
thrombosis, hemorrhage, DIC, infection, weight loss,
bone pain, elevated uric acid, and liver, spleen, and
lymph node enlargement
Clonal disorder in that a single progenitor cell
undergoes malignant transformation
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Lymphadenopathy


Enlarged lymph nodes that become palpable
and tender
Local lymphadenopathy


Drainage of an inflammatory lesion located near
the enlarged node
General lymphadenopathy

Occurs in the presence of malignant or
nonmalignant disease
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Lymphadenopathy

Causes




Neoplastic disease
Immunologic or inflammatory conditions
Endocrine disorders
Lipid storage diseases
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Lymphadenopathy
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Malignant Lymphomas


Malignant transformation of a lymphocyte and
proliferation of lymphocytes, histiocytes, their
precursors, and derivatives in lymphoid tissues
Two major categories



Hodgkin lymphoma
• Linked to EBV
Non-Hodgkin lymphoma
Lymphoblastic lymphoma
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Hodgkin Lymphoma

Reed-Sternberg cells in the lymph nodes




These cells necessary for diagnosis, but not specific
to Hodgkin lymphoma
Classical Hodgkin lymphoma
Nodular lymphocyte predominant Hodgkin
lymphoma
B cell in the germinal center that has not undergone
successful immunoglobulin gene rearrangement but
has undergone apoptosis
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Hodgkin Lymphoma

Physical findings


Symptoms


Fever, weight loss, night sweats, pruritus
Laboratory findings


Adenopathy, mediastinal mass, splenomegaly, and
abdominal mass
Thrombocytosis, leukocytosis, eosinophilia, elevated
erythrocyte sedimentation rate (ESR), elevated
alkaline phosphatase
Paraneoplastic syndromes
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Hodgkin Lymphoma
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Hodgkin Lymphoma
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Non-Hodgkin Lymphoma



Generic term for diverse group of
lymphomas
The lymphomas can be differentiated based
on etiology, unique features, and response to
therapies
Non-Hodgkin lymphomas are linked to
chromosome translocations, viral and
bacterial infections, environmental agents,
immunodeficiencies, and autoimmune
disorders
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Non-Hodgkin Lymphoma


Clonal expansion of B cells (85%), T cells,
and/or NK cells
Changes in proto-oncogenes and tumorsuppressor genes contribute to cell
immortality and thus an increase in
malignant cells
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Burkitt Lymphoma


Most common type of non-Hodgkin
lymphoma in children
A very fast-growing tumor of the jaw and
facial bones

Epstein-Barr virus is found in nasopharyngeal
secretions of individuals
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Burkitt Lymphoma
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Plasma Cell Malignancies


Multiple Myeloma
Waldenström
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Multiple Myeloma



Proliferation of plasma cells
The tumor may be solitary or multifocal
(multiple myeloma)
The malignant plasma cells produce
abnormally large amounts of one class of
immunoglobulin or incomplete immunoglobulin

The unattached light chains of the immunoglobulins
(Bence Jones proteins) can pass through the
glomerulus and damage the renal tubular cells
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Multiple Myeloma



Increased osteoclastic bone destruction
Hypercalcemia (13%), renal failure (19%),
anemia (72%), bone lesions (80%)
Clinical manifestations



Cortical and medullary bone loss
Skeletal pain
Recurring infections due to loss of the humoral
immune response
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Alterations in Splenic Function





Splenomegaly
Hypersplenism
Congestive splenomegaly
Infiltrative splenomegaly
Removal of the spleen


Increased WBCs and platelets
RBC abnormalities
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Disorders of Platelets

Thrombocytopenia


Platelet count <100,000/mm3
• <50,000/mm3—hemorrhage from minor trauma
• <15,000/mm3—spontaneous bleeding
• <10,000/mm3—severe bleeding
Causes:
• Hypersplenism, autoimmune disease, hypothermia, and
viral or bacterial infections that cause DIC
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Disorders of Platelets

Immune thrombocytopenic purpura (ITP)

IgG antibody targets platelet glycoproteins
 Antibody-coated platelets are sequestered and
removed from the circulation
 Acute form develops after viral infections
• One of the most common childhood bleeding disorders
 Manifestations
• Petechiae and purpura, progressing to major hemorrhage
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Disorders of Platelets

Thrombotic thrombocytopenic purpura (TTP)

A thrombotic microangiopathy
• Platelets aggregate, form microthrombi, and cause
occlusion of arterioles and capillaries


Chronic relapsing TTP
Acute idiopathic TTP
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Disorders of Platelets

Essential (primary) thrombocythemia


Thrombocythemia is characterized by platelet
counts >600,000/mm3
Myeloproliferative disorder of platelet precursor
cells
• Megakaryocytes in the bone marrow are produced in
excess

Microvasculature thrombosis occurs
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Alterations of Platelet Function



Qualitative alterations demonstrate an
increased bleeding time in the presence of a
normal platelet count
Disorders result from platelet membrane
glycoprotein and von Willebrand factor
deficiencies
Manifestations


Petechiae, purpura, mucosal bleeding, gingival
bleeding, and spontaneous bruising
Disorders can be congenital or acquired
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Alterations of Coagulation

Vitamin K deficiency


Vitamin K is necessary for synthesis and regulation of
prothrombin, the prothrombin factors (II, VII, XI, X), and
proteins C and S (anticoagulants)
Liver disease

Causes broad range of hemostasis disorders
• Defects in coagulation, fibrinolysis, and platelet number and
function
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Disseminated Intravascular
Coagulation (DIC)

Complex, acquired disorder: clotting and
hemorrhage simultaneously occur



Sepsis, cancer, trauma, blood transfusion
Result of increased protease activity in the
blood caused by unregulated release of
thrombin with subsequent fibrin formation and
accelerated fibrinolysis
Endothelial damage is primary initiator
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Disseminated Intravascular
Coagulation (DIC)


Blockage of blood flow to organs, resulting in
multiple organ failure
Magnitude of clotting may result in consumption
of platelets and clotting factors, leading to
severe bleeding
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Disseminated Intravascular
Coagulation (DIC)


The amount of activated thrombin exceeds
the body’s antithrombins and the thrombin
does not remain localized
The widespread thromboses created cause
widespread ischemia, infarction, and organ
hypoperfusion
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Disseminated Intravascular
Coagulation (DIC)



By activating the fibrinolytic system (plasmin),
person’s fibrin degradation product and D-dimer
levels increase
Due to the person’s clinical state, the disorder
has a high mortality rate
Treatment is to remove the stimulus
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Disseminated Intravascular
Coagulation (DIC)

Clinical signs and symptoms demonstrate
wide variability




Bleeding from venipuncture sites
Bleeding from arterial lines
Purpura, petechiae, and hematomas
Symmetric cyanosis of the fingers and toes
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Thromboembolic Disease

Arterial thrombi


Venous thrombi


Defects in proteins involved in hemostasis
Variety of clinical disorders or conditions
Hypercoagulabilty (thrombophilia)



Acquired
Mutations in coagulation proteins, fibrinolytic
proteins, platelet receptors
Triad of Virchow
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