270
U N I T 3
Hematopoietic Function
junctions. For example, the regulatory control of cap-
illary permeability in the skin and mucosal surfaces is
far different from that in the brain. Common sites for
spontaneous bleeding from platelet disorders are the
skin and mucous membranes of the nose, mouth, gas-
trointestinal tract, and uterine cavity. Cutaneous bleed-
ing is seen as purple areas of bruising (purpura) and
pinpoint hemorrhages (petechiae) in dependent areas
where the capillary pressure is higher. Petechiae are seen
almost exclusively in conditions of platelet deficiency,
not platelet dysfunction. They are also seen in condi-
tions of poor collagen synthesis and impaired formation
of capillary intercellular junctions
15
(Fig. 12-4). Because
tight regulation of capillary permeability in the brain is
essential to prevent intercellular leakage, nontraumatic
intracranial bleeding is relatively rare, even in persons
with severe thrombocytopenia.
16
The major causes of thrombocytopenia are decreased
platelet production, decreased platelet survival, splenic
sequestration, and dilution.
3,4,16
Decreased platelet pro-
duction due to loss of bone marrow function may occur
because of congenital anemia (e.g., Wiskott-Aldrich syn-
drome [see Chapter 16]), acquired anemia (e.g., aplastic
anemia [see Chapter 13]), bone marrow infiltration by
malignant cells (e.g., leukemia), or bone marrow depres-
sion (e.g., radiation therapy, chemotherapy). Infection
with human immunodeficiency virus (HIV) or cytomeg-
alovirus may suppress the production of megakaryo-
cytes, the platelet precursors.
Reduced platelet survival is caused by a variety of
immune and nonimmune mechanisms. Platelet destruc-
tion may be caused by antiplatelet antibodies. These
antibodies may be directed against platelet self-antigens
or against antigens formed on the platelets from prior
blood transfusions or pregnancy. In acute disseminated
intravascular clotting or thrombotic thrombocytopenic
purpura (TTP), excessive platelet consumption leads to
a deficiency.
Production of platelets may be normal, but exces-
sive pooling of platelets in the spleen may occur (splenic
sequestration). When necessary, hypersplenic thrombo-
cytopenia may be treated with splenectomy. Massive
blood or plasma transfusions may cause a dilutional
thrombocytopenia because blood stored for more than
24 hours has no viable platelets.
Immune Thrombocytopenic Purpura.
Immune
thrombocytopenic purpura (ITP) is an autoimmune
disorder that results in platelet antibody formation
and excess destruction of platelets.
7,18
The thrombo-
cytopenia that occurs in ITP is thought to result from
multiple mechanisms, including antiplatelet antibodies
against glycoproteins (IIb/IIIa and Ib/IX) in the platelet
membrane. The platelets are made more susceptible to
phagocytosis because of the antibodies and are subse-
quently destroyed in the spleen. The disorder can occur
in the absence of any known risk factors (primary or
idiopathic ITP) or as a secondary disorder due to an
underlying condition; it can also be classified as acute
(duration of 6 months or less) or chronic. Secondary
forms of ITP may be associated with acquired
immunodeficiency syndrome (AIDS), systemic lupus
erythematosus, antiphospholipid syndrome, chronic
lymphocytic leukemia, lymphoma, hepatitis C, and
drugs such as heparin and quinidine.
About half of the cases of ITP occur as an acute
primary disorder in children, affecting both boys and
girls.
18
The disorder occurs in young children (5 years
of age), commonly following a viral infection. It is
characterized by sudden onset of petechiae and pur-
pura and is usually a self-limited disorder requiring no
treatment. Most children recover in a few weeks. In
contrast, primary ITP is often a chronic disorder in
adults with an insidious onset that seldom follows an
infection. Peak incidence is between the ages of 18 and
40 years, and is seen three times as often in women as
in men.
Manifestations of ITP include a history of easy
bruising, bleeding from gums, epistaxis, melena, and
abnormal menstrual bleeding in those with moderately
reduced platelet counts. Because the spleen is the site
of platelet destruction, splenic enlargement may occur.
The condition may be discovered incidentally or as
a result of signs of bleeding, often into the skin (i.e.,
purpura and petechiae) or oral mucosa. About half of
adults with primary ITP present with a platelet count
of less than 10,000/
μ
L and are at risk for internal
hemorrhage.
18
Diagnosis of ITP usually is based on severe thrombo-
cytopenia (platelet counts <20,000 to 30,000/
μ
L) and
exclusion of other causes. Tests for the platelet-bound
antibodies are available but lack specificity (e.g., they
react with platelet antibodies from other sources). The
secondary form of ITP sometimes mimics the idio-
pathic form of the disorder; therefore, the diagnosis
is made only after excluding other known causes of
thrombocytopenia.
The decision to treat ITP is based on the platelet
count and the degree of bleeding. Many persons with
FIGURE 12-4.
Leg of a 9-year-old boy with petechiae due to
vitamin C deficiency. (From Duggan CP, Westra SJ, Rosenberg
AE. Case 23–2007: A 9-year-old body with bone pain, rash, and
gingival hyperplasia. N Engl J Med. 2007;357:395. Copyright ©
2007. Massachusetts Medical Society.)
