C h a p t e r 1 2
Disorders of Hemostasis
269
thrombosis, repeated fetal loss, and thrombocytopenia.
The disorder can manifest either as a primary condition
occurring in isolation with signs of hypercoagulability
or as a secondary condition most often associated with
connective tissue disorders, particularly systemic lupus
erythematosus (SLE).
Persons with the disorder present with a variety of
clinical manifestations, typically those characterized by
recurrent venous and arterial thrombi. Cardiac valvu-
lar vegetations associated with thrombi adherence and
thrombocytopenia due to excessive platelet consump-
tion may also occur. Venous thrombosis, especially
in the deep leg veins, occurs in up to 50% of persons
with the syndrome, half of whom develop pulmonary
emboli. Arterial thromboses are less common than
venous thromboses and most frequently manifest with
features of ischemia and infarction. The cerebral arteries
are the most commonly affected. Other sites for arterial
thrombosis are the coronary arteries of the heart and
the retinal, renal, and peripheral arteries. Women with
the disorder commonly have a history of recurrent preg-
nancy losses after the 10th week of gestation because of
ischemia and thrombosis of the placental vessels. These
women also have increased risk of giving birth to a pre-
mature infant owing to pregnancy-associated hyperten-
sion and uteroplacental insufficiency.
In most persons with antiphospholipid syndrome,
the thrombotic events occur as a single episode at one
anatomic site. In some persons recurrences may occur
months or years later and mimic the initial event.
Occasionally, someone may present with multiple vascu-
lar occlusions involving many organ systems. This rapid-
onset condition is termed
catastrophic antiphospholipid
syndrome
and is associated with a high mortality rate.
Treatment of the syndrome focuses on removal or
reduction in factors that predispose to thrombosis,
including tobacco cessation and avoidance of estrogen-
containing oral contraceptives by women. The acute
thrombotic event is treated with anticoagulants (hepa-
rin and warfarin) and immune suppression in refractory
cases. Aspirin and anticoagulant drugs may be used to
prevent future thrombosis.
13
Bleeding Disorders
Bleeding disorders or impairment of blood coagulation
can result from defects in any of the factors that contrib-
ute to hemostasis. Bleeding can occur as a result of dis-
orders associated with platelet count, platelet function,
coagulation factors, or blood vessel integrity.
Platelet Disorders
Bleeding due to platelet disorders reflects a failure of
activated platelets to bring about hemostasis through
the formation of a platelet plug at the site of injury to
the blood vessel wall, an injury that causes physical and
biochemical disruption of the endothelium.
Thrombocytopenia
Thrombocytopenia
refers to a decrease in the number
of circulating platelets to a level less than 100,000/
μ
L.
15,16
The greater the decrease in the platelet count,
the greater the risk of bleeding. However, spontaneous
bleeding usually does not occur until the platelet count
falls below 20,000/
μ
L.
The anatomic sites of bleeding in persons with
thrombocytopenia are the intercellular junctions in the
postcapillary venules.
16
Key molecules in the junctions
include adhesive proteins and associated intracellular
binding components (see Chapter 1). Different vascular
beds with varying functions require different types of
SUMMARY CONCEPTS
■■
Hypercoagulability states increase the risk
of clot or thrombus formation in either the
arterial or venous circulations. Arterial thrombi
are associated with conditions that produce
an increase in platelet numbers or turbulence
in blood flow with platelet adhesion. Venous
thrombi are associated with inherited or
acquired conditions that cause a decrease in
anticoagulation factors or produce a stasis
of blood, thereby causing an increase in
procoagulation factors.
■■
Increased platelet function usually results from
disorders such as atherosclerosis that damage
the vascular endothelium and disturb blood flow,
or from conditions such as smoking that increase
sensitivity of platelets to factors that promote
adhesiveness and aggregation.
■■
Increased activity of the coagulation system
results from hereditary (factor V Leiden mutation)
or acquired disorders (immobility, hyperviscosity
syndromes) causing alterations in the
components of the coagulation system (i.e., an
increase in procoagulation factors or a decrease
in anticoagulation factors).
■■
Thrombocytosis refers to an increase in the
platelet count that can occur as an essential
(primary thrombocytosis) or a reactive
process (secondary thrombocytosis).The
antiphospholipid syndrome, another cause
of venous and arterial clotting, manifests as a
primary or a secondary disorder associated with
systemic lupus erythematosus. It is associated
with antiphospholipid antibodies, which promote
thrombosis throughout the body.
