PATHOPHYSIOLOGIC MANIFESTATIONS

Leukocytosis
Leukocytosis is an elevation in the number of white blood cells (WBCs). All types of
WBCs may be increased, or only
one type. (See WBC types and functions.) Leukocytosis is a normal physiologic
response to infection or inflammation.
Other factors, such as temperature changes, emotional disturbances, anesthesia,
surgery, strenuous exercise,
pregnancy, and some drugs, hormones, and toxins can also cause leukocytosis.
Abnormal leukocytosis occurs in
malignancies and bone marrow disorders.
Leukopenia
Leukopenia is a deficiency of WBCs all types or only one type. It can be caused
by a number of conditions or
diseases, such as human immunodeficiency virus (HIV) infection, prolonged stress,
bone marrow disease or destruction,
radiation or chemotherapy, lupus erythematosus, leukemia, thyroid disease, or
Cushing syndrome. Because WBCs fight
infection, leukopenia increases the risk of infectious illness.
Thrombocytosis
Thrombocytosis is an excess of circulating platelets to greater than 400,000/l.
Thrombocytosis may be primary or
secondary.
Primary thrombocytosis
In primary thrombocytosis, the number of platelet precursor cells, called
megakaryocytes, is increased and the platelet
count is greater than1 million/l. The condition may result from an intrinsic
abnormality of platelet function and increased
platelet mass. It may accompany polycythemia vera or chronic granulocytic
leukemia. In the presence of thrombocytosis,
both hemorrhage and thrombosis may occur. This paradox occurs because
accelerated clotting results in a generalized
activation of prothrombin and a consequent excess of thrombin clots in the
microcirculation. This process consumes
exorbitant amounts of coagulation factors and thereby increases the risk of
hemorrhage.
Secondary thrombocytosis
Secondary thrombocytosis is a result of an underlying cause, such as stress,
exercise, hemorrhage, or hemolytic anemia.
Stress and exercise release stored platelets from the spleen. Hemorrhage or
hemolytic anemia signal the bone marrow to
produce more megakaryocytes.
Thrombocytosis may also occur after a splenectomy. Because the spleen is the
primary site of platelet storage and
destruction, platelet count may rise after its removal until the bone marrow begins
producing fewer platelets.

DISORDERS
Specific causes of hematologic disorders include trauma, chronic disease, surgery,
malnutrition, drug, exposure to toxins
or radiation, and genetic or congenital defects that disrupt production or function of
blood cells.
Aplastic anemias
Aplastic or hypoplastic, anemias result from injury to or destruction of stem cells in
bone marrow or the bone marrow matrix, causing pancytopenia (anemia, leukopenia,
and thrombocytopenia) and bone marrow hypoplasia. Although commonly used
interchangeably with other terms for bone marrow failure, aplastic anemia properly
refers to pancytopenia resulting from the decreased functional capacity of a
hypoplastic, fatty bone marrow.
These disorders generally produce fatal bleeding or infection, especially when
they're idiopathic or caused by chloramphenicol (Chloromycetin) use or infectious
hepatitis. The death rate for severe aplastic anemia is 80% to 90%.
Causes
Possible causes of aplastic anemia are:
radiation (about half of such anemias)
drugs (antibiotics, anticonvulsants), or toxic agents (such as benzene or
chloramphenicol [Chloromycetin])
autioimmune reactions (unconfirmed), severe disease (especially hepatitis), or
preleukemic and neoplastic
infiltration of bone marrow
congenital (idiopathic anemias): two identified forms of aplastic anemia are
congenital hypoplastic or Blackfan-Diamond anemia (develops between
ages 2 and 3 months); and Fanconi syndrome (develops between birth and
10 years of age).
Pathophysiology
Aplastic anemia usually develops when damaged or destroyed stem cells inhibit
blood cell production. Less commonly,
they develop when damaged bone marrow microvasculature creates an unfavorable
environment for cell growth and
maturation.
Signs and symptoms
Signs and symptoms of aplastic anemia vary with the severity of pancytopenia, but
develop insidiously in many cases.
They may include:
progressive weakness and fatigue, shortness of breath, headache, pallor, and
ultimately tachycardia and heart
failure due to hypoxia and increased venous return
ecchymosis, petechiae, and hemorrhage, especially from the mucous membranes
(nose, gums, rectum, vagina) or
into the retina or central nervous system due to thrombocytopenia
infection (fever, oral and rectal ulcers, sore throat) without characteristic
inflammation due to neutropenia
(neutrophil deficiency).
Iron deficiency anemia

Iron deficiency anemia is a disorder of oxygen transport in which hemoglobin

synthesis is deficient. A common disease worldwide, iron deficiency anemia affects
10% to 30% of the adult population of the United States. Iron deficiency anemia
occurs most commonly in premenopausal women, infants (particularly premature or
low-birth-weight infants), children, and adolescents (especially girls). The prognosis
after replacement therapy is favorable.
Causes
Possible causes of iron deficiency anemia are: inadequate dietary intake of iron (less
than 1 to 2 mg/day), as in prolonged nonsupplemented breast-feeding or
bottle-feeding of infants or during periods of stress, such as rapid growth, in children
and adolescents
iron malabsorption, as in chronic diarrhea, partial or total gastrectomy, and
malabsorption syndromes, such as
celiac disease and pernicious anemia
blood loss due to drug-induced GI bleeding (from anticoagulants, aspirin, steroids) or
heavy menses, hemorrhage
from trauma, peptic ulcers, cancer, or varices
pregnancy, which diverts maternal iron to the fetus for erythropoiesis
intravascular hemolysis-induced hemoglobinuria or paroxysmal nocturnal
hemoglobinuria
mechanical trauma to RBCs caused by a prosthetic heart valve or vena cava filters.
Pathophysiology
Iron deficiency anemia occurs when the supply of iron is inadequate for optimal
formation of RBCs, resulting in smaller
(microcytic) cells with less color (hypochromic) on staining. Body stores of iron,
including plasma iron, become depleted,
and the concentration of serum transferrin, which binds with and transports iron,
decreases. Insufficient iron stores lead
to a depleted RBC mass with subnormal hemoglobin concentration, and, in turn,
subnormal oxygen-carrying capacity of
the blood.
Signs and symptoms
Because iron deficiency anemia progresses gradually, many patients exhibit only
symptoms of an underlying condition.
They tend not to seek medical treatment until anemia is severe.
At advanced stages, signs and symptoms include:
dyspnea on exertion, fatigue, listlessness, pallor, inability to concentrate, irritability,
headache, and a susceptibility
to infection due to decreased oxygen-carrying capacity of the blood caused by
decreased hemoglobin levels
increased cardiac output and tachycardia due to decreased oxygen perfusion
coarsely ridged, spoon-shaped (koilonchyia), brittle, and thin nails due to decreased
capillary circulation
sore, red, and burning tongue due to papillae atrophy
sore, dry skin in the corners of the mouth due to epithelial changes.
Pernicious anemia
Pernicious anemia, the most common type of megaloblastic anemia, is caused by
malabsorption of vitamin B 12.

AGE ALERT Onset typically occurs between the ages of 50 and 60 years, and
incidence increases with age. It's
rare in children.
CULTURAL DIVERSITY Pernicious anemia primarily affects people of northern
European ancestry. In the
United States, it's most common in New England and the Great Lakes region
because of ethnic distribution.
If not treated, pernicious anemia is fatal. Its manifestations subside with treatment,
but some neurologic deficits may be
permanent.
Pathophysiology
Pernicious anemia is characterized by decreased production of hydrochloric acid in
the stomach, and a deficiency of
intrinsic factor, which is normally secreted by the parietal cells of the gastric mucosa
and is essential for vitamin B 12
absorption in the ileum. The resulting vitamin B 12 deficiency inhibits cell growth,
particularly of RBCs, leading to
production of few, deformed RBCs with poor oxygen-carrying capacity. It also
causes neurologic damage by impairing
myelin formation.
Causes
Possible causes of pernicious anemia include:
genetic predisposition (suggested by familial incidence)
immunologically related diseases, such as thyroiditis, myxedema, and Graves'
disease (significantly higher
incidence in these patients)
partial gastrectomy (iatrogenic induction)
older age (progressive loss of vitamin B 12 absorption).
AGE ALERT The elderly often have a dietary deficiency of B 12 in addition to or
instead of poor absorption.
Signs and symptoms
Characteristically, pernicious anemia has an insidious onset but eventually causes
an unmistakable triad of symptoms:
weakness due to tissue hypoxia
sore tongue due to atrophy of the papillae
numbness and tingling in the extremities as a result of interference with
impulse transmission from demyelination.
Other common manifestations include:
pale appearance of lips and gums
faintly jaundiced sclera and pale to bright yellow skin due to hemolysisinduced hyperbilirubinemia
high susceptibility to infection, especially of the genitourinary tract.
Pernicious anemia may also have gastrointestinal, neurologic, and
cardiovascular effects.
Gastrointestinal symptoms include:
nausea, vomiting, anorexia, weight loss, flatulence, diarrhea, and constipation
from disturbed digestion due to gastric mucosal atrophy and decreased
hydrochloric acid production gingival bleeding and tongue inflammation (may
hinder eating and intensify anorexia).

Neurologic symptoms include:

neuritis; weakness in extremities
peripheral numbness and paresthesia
disturbed position sense
lack of coordination; ataxia; impaired fine finger movement
positive Babinski and Romberg signs
light-headedness
altered vision (diplopia, blurred vision), taste, and hearing (tinnitus); optic
muscle atrophy
loss of bowel and bladder control; and, in males, impotence, due to
demyelination (initially affects peripheral nerves
but gradually extends to the spinal cord) caused by vitamin B 12 deficiency
irritability, poor memory, headache, depression, and delirium (some
symptoms are temporary, but irreversible
central nervous system [CNS] changes may have occurred before
treatment).
Cardiovascular symptoms include:
low hemoglobin levels due to widespread destruction of RBCs caused by
increasingly fragile cell membranes
palpitations, wide pulse pressure, dyspnea, orthopnea, tachycardia,
premature beats, and, eventually, heart failure
due to compensatory increased cardiac output.
Complications
Possible complications include:
hypokalemia (first week of treatment)
permanent CNS symptoms (if the patient is not treated within 6 months of
appearance of symptoms)
gastric polyps
stomach cancer.
Sideroblastic anemias
Sideroblastic anemias are a group of heterogenous disorders with a common defect:
they fail to use iron in hemoglobin
synthesis, despite the availability of adequate iron stores. These anemias may be
hereditary or acquired. The acquired
form can be primary or secondary. Hereditary sideroblastic anemia commonly
responds to treatment with pyridoxine
(vitamin B6). The primary acquired (idiopathic) form, known as refractory anemia with
ringed sideroblasts, resists
treatment and is usually fatal within 10 years of the onset of complications or a
concomitant disease. This form is most
common in the elderly. It's commonly associated with thrombocytopenia or
leukopenia as part of a myelodysplastic
syndrome. Correction of the secondary acquired form depends on the cause.

RINGED SIDEROBLAST
Electron microscopy shows large iron deposits in the mitochondria that surround the
nucleus, forming the
characteristic ringed sideroblast of hemochromatosis.

Cause
Hereditary sideroblastic anemia appears to be transmitted by:
X-linked inheritance, occurring mostly in young males (female carriers usually show
no signs of this disorder).
The acquired form may be secondary to:
ingestion of or exposure to toxins (such as alcohol and lead) or drugs (such as
isoniazid [Laniazid] and
chloramphenicol [Chloromycetin])
other diseases, such as rheumatoid arthritis, lupus erythematosus, multiple
myeloma, tuberculosis, and severe
infections.
Pathophysiology
In sideroblastic anemia, normoblasts fail to use iron to synthesize hemoglobin. As a
result, iron is deposited in the
mitochondria of normoblasts, which are then termed ringed sideroblasts. Iron toxicity
can cause organ damage;
untreated, it can damage the nuclei of RBC precursors.
Signs and symptoms
Possible signs and symptoms of sideroblastic anemia include:
anorexia, fatigue, weakness, dizziness, pale skin and mucous membranes,
and, occasionally, enlarged lymph
nodes due to iron toxicity
dyspnea, exertional angina, slight jaundice, and hepatosplenomegaly due to
heart and liver failure caused by
excessive iron accumulation in these organs
increased GI absorption of iron, causing signs of hemosiderosis (hereditary
sideroblastic anemia)
other symptoms depend on the underlying cause (secondary sideroblastic
anemia).
Complications
Possible complications are:
heart, liver, and pancreatic disease
respiratory complications
acute myelogenous leukemia.
Thalassemia
Thalassemia, a hereditary group of hemolytic anemias, is characterized by defective
synthesis in the polypeptide chains
of the protein component of hemoglobin. Consequently, RBC synthesis is also
impaired.
CULTURAL DIVERSITY Thalassemia is most common in people of Mediterranean
ancestry (especially Italian
and Greek), but also occurs in people whose ancestors originated in Africa, southern
China, southeast Asia,
and India.
In b-thalassemia, the most common form of this disorder, synthesis of the beta
polypeptide chain is defective. It occurs in
three clinical forms: major, intermedia, and minor. The severity of the resulting
anemia depends on whether the patient is
homozygous or heterozygous for the thalassemic trait. The prognosis varies:

thalassemia major: patients seldom survive to adulthood

thalassemia intermedia: children develop normally into adulthood, although puberty
is usually delayed
thalassemia minor: normal life span.
Causes
Causes of thalassemia are:
homozygous inheritance of the partially dominant autosomal gene (thalassemia
major or thalassemia intermedia)
heterozygous inheritance of the same gene (thalassemia minor).
Pathophysiology
Total or partial deficiency of beta polypeptide chain production impairs hemoglobin
synthesis and results in continual
production of fetal hemoglobin, lasting even past the neonatal period. Normally,
immunoglobulin synthesis switches from
gamma- to beta-polypeptides at the time of birth. This conversion doesn't happen in
thalassemic infants. Their red cells
are hypochromic and microcytic.
Signs and symptoms
Possible signs and symptoms of thalassemia major (also known as Cooley's anemia,
Mediterranean disease, and erythroblastic anemia) are:
healthy infant at birth, during second 6 months if life develops severe anemia, bone
abnormalities, failure to thrive, and life-threatening complications
pallor and yellow skin and sclera in 3- to 6-month-old infants
splenomegaly or hepatomegaly, with abdominal enlargement; frequent infections;
bleeding tendencies (especially nose bleeds); anorexia
small body, large head (characteristic features), and possible mental retardation
possible features similar to Down syndrome in infants, due to thickened bone at the
base of the nose from bone
marrow hyperactivity.
Signs and symptoms of thalassemia intermedia are:
some degree of anemia, jaundice, and splenomegaly
possibly signs of hemosiderosis due to increased intestinal absorption of iron.
Signs of thalassemia minor are:
mild anemia (usually produces no symptoms and is often overlooked; it should be
differentiated from iron deficiency
anemia).
Complications
Possible complications of thalassemia include:
pathologic fractures due to expansion of the marrow cavities with thinning of the long
bones
cardiac arrhythmias
heart failure.
Disseminated intravascular coagulation
Disseminated intravascular coagulation (DIC) occurs as a complication of diseases
and conditions that accelerate
clotting, causing small blood vessel occlusion, organ necrosis, depletion of
circulating clotting factors and platelets,
activation of the fibrinolytic system, and consequent severe hemorrhage. Clotting in
the microcirculation usually affects

the kidneys and extremities but may occur in the brain, lungs, pituitary and adrenal
glands, and GI mucosa. DIC, also
called consumption coagulopathy or defibrination syndrome, is generally an acute
condition but may be chronic in cancer
patients. Prognosis depends on early detection and treatment, the severity of the
hemorrhage, and treatment of the
underlying disease.
Causes
Causes of DIC include:
infection, including gram-negative or gram-positive septicemia and viral, fungal,
rickettsial, or protozoal infection
obstetric complications, including abruption placentae, amniotic fluid embolism,
retained dead fetus, septic
abortion, eclampsia
neoplastic disease, including acute leukemia, metastatic carcinoma, aplastic anemia
disorders that produce necrosis, including extensive burns and trauma, brain tissue
destruction, transplant
rejection, hepatic necrosis
other conditions, including heatstroke, shock, poisonous snakebite, cirrhosis, fat
embolism, incompatible blood
transfusion, cardiac arrest, surgery requiring cardiopulmonary bypass, giant
hemangioma, severe venous
thrombosis, and purpura fulminans.
Pathophysiology
It isn't clear why certain disorders lead to DIC or whether they use a common
mechanism. In many patients, the triggering
mechanisms may be the entrance of foreign protein into the circulation and vascular
endothelial injury.
Regardless of how DIC begins, the typical accelerated clotting results in generalized
activation of prothrombin and a
consequent excess of thrombin. The thrombin converts fibrinogen to fibrin, producing
fibrin clots in the microcirculation.
This process uses huge amounts of coagulation factors (especially fibrinogen,
prothrombin, platelets, and factors V and
VIII), causing hypofibrinogenemia, hypoprothrombinemia, thrombocytopenia, and
deficiencies in factors V and VIII.
Circulating thrombin also activates the fibrinolytic system, which dissolves fibrin clots
into fibrin degradation products.
Hemorrhage may be mostly the result of the anticoagulant activity of fibrin
degradation products as well as depletion of
plasma coagulation factors.
Signs and symptoms
Signs and symptoms of DIC caused by the anticoagulant activity of fibrin degradation
products and depletion of plasma
coagulation factors include:
abnormal bleeding
cutaneous oozing of serum
petechiae or blood blisters
bleeding from surgical or IV sites
bleeding from the GI tract

epistaxis
hemoptysis.
Other signs and symptoms are:
cyanotic, cold, mottled fingers and toes, due to fibrin clots in the microcirculation
resulting in tissue ischemia
severe muscle, back, abdominal, and chest pain from tissue hypoxia
nausea and vomiting (may be a manifestation of GI bleeding)
shock due to hemorrhage
confusion, possibly due to cerebral thrombus and decreased cerebral perfusion
dyspnea due to poor tissue perfusion and oxygenation
oliguria due to decreased renal perfusion.
Erythroblastosis fetalis
Erythroblastosis fetalis, a hemolytic disease of the fetus and newborn, stems from an
incompatibility of fetal and maternal
blood; that is, mother and fetus have different ABO blood types or the fetus is Rh
positive and the mother is Rh negative.
The mother's immune system generates antibodies against fetal red cells.
The effects of hemolytic disease are more severe in Rh incompatibility than ABO
incompatibility. ABO incompatibility may
resolve after birth without life-threatening complications. ABO incompatibility occurs
in about 25% of all pregnancies, but
only 1 in 10 cases results in hemolytic disease. Rh incompatibility occurs in less than
10% of pregnancies and rarely
causes hemolytic disease in the first pregnancy.
In severe, untreated erythroblastosis fetalis, the prognosis is poor, especially if brain
and spinal cord become infiltrated
with bilirubin (kernicterus). About 70% of these infants die, usually within the first
week of life; survivors inevitably have
severe neurologic damage, including sensory impairment, mental deficiencies, and
cerebral palsy. Most fetuses with
hydrops fetalis (the most severe form of this disorder, associated with profound
anemia and edema) are stillborn; the few
who are delivered alive rarely survive longer than a few hours.
Causes
Erythroblastosis fetalis is caused by:
ABO incompatibility
Rh isoimmunization.
Pathophysiology
The pathophysiologies of ABO and Rh incompatibility are different.
ABO incompatibility. Each blood group has specific antigens on RBCs and specific
antibodies in the serum. As in
transfusion, the maternal immune system forms antibodies against fetal cells when
blood groups differ. Most commonly,
the mother has blood type O and the fetus has type A or B. Of course, a mother with
type A or B will not form antibodies
against a type O fetus, who has no fetal blood type antigens. Because the blood of
most adults already contains anti-A or
anti-B antibodies, ABO incompatibility can cause hemolytic disease even if fetal
erythrocytes don't escape into the

maternal circulation during pregnancy.

Rh incompatibility. During her first pregnancy, an Rh-negative female becomes
sensitized (during delivery or abortion)
by exposure to Rh-positive fetal blood antigens inherited from the father. A female
may also become sensitized from
receiving blood transfusions with alien Rh antigens; from inadequate doses of Rh o
(D) (RhoGAM); or from failure to
receive Rho (D) after significant fetal-maternal leakage during abruption placentae
(premature detachment of the
placenta).
A subsequent pregnancy with an Rh-positive fetus provokes maternal production of
agglutinating antibodies, which cross
the placental barrier, attach to Rh-positive cells in the fetus, and cause hemolysis
and anemia. To compensate, the fetal
blood forming organs step up the production of RBCs, and erythroblasts (immature
RBCs) appear in the fetal circulation.
Extensive hemolysis releases more unconjugated bilirubin than the liver can
conjugate and excrete, causing
hyperbilirubinemia and hemolytic anemia.
Signs and symptoms
Signs and symptoms of erythroblastosis fetalis include:
jaundice due to large amounts of unconjugated bilirubin released by hemolysis
anemia due to hemolysis
hepatosplenomegaly.
Complications
Complications of erythroblastosis fetalis include:
fetal death in utero
severe anemia
heart failure
kernicterus.
Idiopathic thrombocytopenic purpura
Idiopathic thrombocytopenic purpura (ITP) is a deficiency of platelets that occurs
when the immune system destroys the
body's own platelets. ITP may be acute, as in postviral thrombocytopenia, or chronic,
as in essential thrombocytopenia or
autoimmune thrombocytopenia.
AGE ALERT Acute ITP usually affects children between the ages of 2 and 6 years;
chronic ITP mainly affects
adults younger than age 50, especially women between the ages of 20 and 40.
The prognosis for acute ITP is excellent; nearly four of five patients recover without
treatment. The prognosis for chronic
ITP is good; remissions lasting weeks or years are common, especially among
women.
Causes
Causes of ITP include:
viral infection
immunization with a live virus vaccine
immunologic disorders
drug reactions.

Pathophysiology
ITP occurs when circulating immunoglobulin G (IgG) molecules react with host
platelets, which are then destroyed in the
spleen and, to a lesser degree, in the liver. Normally, the life span of platelets in
circulation is 7 to 10 days. In ITP,
platelets survive 1 to 3 days or less.
Signs and symptoms
Signs and symptoms of ITP are caused by decreased levels of platelets and may
include:
nose bleeds
oral bleeding
hemorrhages into the skin, mucous membranes, and other tissues causing red
discoloration of skin (purpura)
small purplish hemorrhagic spots on skin (petechiae)
excessive menstrual bleeding.
Polycythemia vera
Polycythemia vera is a chronic disorder characterized by increased RBC mass,
erythrocytosis, leukocytosis,
thrombocytosis, and increased hemoglobin level, with normal or increased plasma
volume. This disease is also known as
primary polycythemia, erythremia, polycythemia rubra vera, splenomegalic
polycythemia, or Vaquez-Osler disease. It
usually occurs between the ages of 40 and 60, most commonly among Jewish males
of European ancestry. It seldom
affects children and doesn't appear to be familial.
The prognosis depends on age at diagnosis, the type of treatment used, and
complications. Mortality is high if
polycythemia is untreated, associated with leukemia, or associated with myeloid
metaplasia (presence of marrow-like
tissue and ectopic hematopoiesis in extramedullary sites, such as liver and spleen,
and nucleated erythrocytes in blood).
Causes
The cause of polycythemia vera is unknown, but is probably related to:
multipotential stem cell defect.
Pathophysiology
In polycythemia vera, uncontrolled and rapid cellular reproduction and maturation
cause proliferation or hyperplasia of all
bone marrow cells (panmyelosis).
Increased RBC mass makes the blood abnormally viscous and inhibits blood flow to
microcirculation. Diminished blood
flow and thrombocytosis set the stage for intravascular thrombosis.
Signs and symptoms
Possible signs and symptoms of polycythemia vera include:
feeling of fullness in the head or headache due to altered hypervolemia and
hyperviscosity
dizziness due to hypervolemia and hyperviscosity
ruddy cyanosis (plethora) of the nose and clubbing of the digits due to thrombosis in
smaller vessels

painful pruritus due to abnormally high concentrations of mast cells in the skin and
their release of heparin and
histamine.
Complications
Possible complications include:
hemorrhage
vascular thromboses
uric acid stones.
Secondary polycythemia
Secondary polycythemia, also called reactive polycythemia, is excessive production
of circulating RBCs due to hypoxia,
tumor, or disease. It occurs in approximately 2 of every 100,000 people living at or
near sea level; the incidence
increases among those living at high altitudes.
Causes
Secondary polycythemia may be caused by:
increased production of erythropoietin.
Pathophysiology
Secondary polycythemia may result from increased production of the hormone
erythropoietin which stimulates bone
marrow to produce RBCs in a compensatory response to several conditions.
These include hypoxemia caused by
such conditions as chronic obstructive pulmonary disease, hemoglobin abnormalities
(such as carboxyhemoglobinemia
in heavy smokers), heart failure (causing a decreased ventilation-perfusion ratio),
right-to-left shunting of blood in the
heart (as in transposition of the great vessels), central or peripheral alveolar
hypoventilation (as in barbiturate
intoxication), and low oxygen content at high altitudes.
Increased production of erythropoietin may also be an inappropriate (pathologic)
response to renal, central nervous
system, or endocrine disorders or to certain neoplasms (such as renal tumors,
uterine myoma, or cerebellar
hemangiomas).
Signs and symptoms
Possible signs and symptoms are:
ruddy cyanotic skin, emphysema, and hypoxemia without hepatomegaly or
hypertension (in the hypoxic patient)
clubbing of the fingers (when the underlying cause is cardiovascular).
Spurious polycythemia
Spurious polycythemia is characterized by an increased hematocrit and a normal or
low RBC total mass. It results from
diminished plasma volume and subsequent hemoconcentration. It is also known as
relative polycythemia, stress
erythrocytosis, stress polycythemia, benign polycythemia, Gaisbck's syndrome, or
pseudopolycythemia. It usually
affects middle-aged people and is more common in men than in women.
Causes

Causes of spurious polycythemia include:

dehydration
hemoconcentration due to stress
high-normal RBC mass and low-normal plasma volume
hypertension
thromboembolic disease
elevated serum cholesterol and uric acid
familial tendency.
Pathophysiology
Conditions that promote severe fluid loss decrease plasma volume and lead to
hemoconcentration. Such conditions
include persistent vomiting or diarrhea, burns, adrenocortical insufficiency,
aggressive diuretic therapy, decreased fluid
intake, diabetic acidosis, and renal disease.
Nervous stress causes hemoconcentration by some unknown mechanism. This form
of erythrocytosis (chronically
elevated hematocrit) is particularly common in the middle-aged man who is a chronic
smoker and has a type A
personality (tense, hard driving, and anxious).
In many patients, an increased hematocrit merely reflects a normally high RBC mass
and low plasma volume. This is
particularly common in patients who don't smoke, aren't obese, and have no history
of hypertension.
Signs and symptoms
Signs and symptoms of spurious polycythemia may include:
headaches or dizziness due to altered circulation secondary to hypervolemia and
hyperviscosity
ruddy appearance caused by cyanosis
slight hypertension from increased blood volume
tendency to hyperventilate when recumbent
cardiac or pulmonary disease.
Thrombocytopenia
Thrombocytopenia, the most common cause of hemorrhagic disorders, is a
deficiency of circulating platelets. It may be
congenital or acquired; the acquired form is more common. Because platelets are
needed for coagulation, this disease
poses a serious threat to hemostasis. The prognosis is excellent in drug-induced
thrombocytopenia if the offending drug
usually carbamazepine (Tegretol) or heparin is withdrawn; in such cases,
recovery may be immediate. In other
types, the prognosis depends on the patient's response to treatment of the
underlying cause.
Causes
Possible causes of thrombocytopenia include:
decreased or defective platelet production in the bone marrow (as in leukemia,
aplastic anemia, or drug toxicity)
increased platelet destruction outside the marrow due to an underlying disorder
(such as cirrhosis of the liver,
disseminated intravascular coagulation, or severe infection)

sequestration (increased amount of blood in a limited vascular area, such as the

spleen)
blood loss.
Pathophysiology
In thrombocytopenia, lack of platelets can cause inadequate hemostasis. Four
mechanisms are responsible: decreased
platelet production, decreased platelet survival, pooling of blood in the spleen, and
intravascular dilution of circulating
platelets. Megakaryocytes, giant cells in the bone marrow, produce platelets. Platelet
production decreases when the
number of megakaryocytes is reduced or when platelet production becomes
dysfunctional.

WHAT HAPPENS IN THROMBOCYTOPENIA

Defective platelet function is characterized in vivo by decreased agglutination and
adhesion at the bleeding site and in
vitro by reduced platelet retention when blood is filtered through a column of packed
glass beads, and diminished
ristocetin-induced platelet aggregation.
Signs and symptoms
Possible signs and symptoms of thrombocytopenia are:
petechiae or blood blisters caused by bleeding into the skin
bleeding into the mucous membrane
malaise, fatigue, and general weakness
large blood-filled blisters in the mouth (in adults).
Complications
Complications include:
hemorrhage
death.
Von Willebrand's disease
Von Willebrand's disease is a hereditary bleeding disorder, occurring more often in
females and characterized by
prolonged bleeding time, moderate deficiency of clotting factor VIII (antihemophilic
factor), and impaired platelet function.
This disease commonly causes bleeding from the skin or mucosal surfaces and, in
females, excessive uterine bleeding.
Bleeding may range from mild and asymptomatic to severe, potentially fatal,
hemorrhage. The prognosis is usually good.
Causes
Von Willebrand's disease is caused by:
inherited autosomal dominant trait.
Recently, an acquired form has been identified in patients with cancer and immune
disorders.
Pathophysiology
A possible mechanism is that mild to moderate deficiency of factor VIII and defective
platelet adhesion prolong
coagulation time. Specifically, this results from a deficiency of von Willebrand's factor
(VWF), which stabilizes the factor
VIII molecule and is needed for proper platelet function.
Signs and symptoms

Prolonged coagulation time may cause:

easy bruising
epistaxis (nose bleed)
bleeding from the gums
petechiae (rarely)
hemorrhage after laceration or surgery (in severe forms)
menorrhagia (in severe forms)
GI bleeding (in severe forms)
excessive postpartum bleeding (uncommon)
massive soft tissue hemorrhage and bleeding into joints (rare).
Complications
A complication of von Willebrand's disease is:
hemorrhage.