Maintenance of the Body
box in Chapter 19 (pp. 700–701) describes
other drugs that dissolve blood clots (such as tPA) and innova-
tive medical techniques for treating clots.
Anything that interferes with the clotting mechanism can result
in abnormal bleeding. Te most common causes are platelet de-
ﬁciency (thrombocytopenia) and deﬁcits of some clotting fac-
tors, which can result from impaired liver function or genetic
conditions such as hemophilia.
A condition in which the number of cir-
culating platelets is deﬁcient,
ne-ah) causes spontaneous bleeding from small blood
vessels all over the body. Even normal movement leads to wide-
spread hemorrhage, evidenced by many small purplish spots,
ke-e), on the skin.
Trombocytopenia can arise from any condition that sup-
presses or destroys the red bone marrow, such as bone marrow
malignancy, exposure to ionizing radiation, or certain drugs. A
platelet count of under 50,000/μl of blood is usually diagnostic
for this condition. ±ransfusions of concentrated platelets pro-
vide temporary relief from bleeding.
Impaired Liver Function
When the liver is unable to synthe-
size its usual supply of clotting factors, abnormal and oFen
severe bleeding occurs. Te causes can range from an easily re-
solved vitamin K deﬁciency (common in newborns) to nearly
total impairment of liver function (as in hepatitis or cirrhosis).
Liver cells require vitamin K to produce clotting factors. Al-
though intestinal bacteria make some vitamin K, we obtain most
of it from vegetables in our diet and dietary deﬁciencies are rarely
a problem. However, vitamin K deﬁciency can occur if fat absorp-
tion is impaired, because vitamin K is a fat-soluble vitamin that is
absorbed into the blood along with fats. In liver disease, the non-
functional liver cells fail to produce not only the clotting factors,
but also bile that is required to absorb fat and vitamin K.
refers to several heredi-
tary bleeding disorders that have similar signs and symptoms.
results from a deﬁciency of
factor VIII (anti-
. It accounts for 77% of cases.
results from a deﬁciency of factor IX. Both types are genetic
conditions that occur primarily in males (X-linked conditions,
discussed in Chapter 29).
, a less severe form seen
in both sexes, is due to a lack of factor XI. Te relative mildness
of hemophilia C, compared to the A and B forms, reﬂects the
fact that the clotting factor (factor IX) that the missing factor XI
activates can also be activated by factor VII (see ²igure 17.14).
Symptoms of hemophilia begin early in life. Even minor tis-
sue trauma causes prolonged and potentially life-threatening
bleeding into tissues. Commonly, the person’s joints become se-
riously disabled and painful because of repeated bleeding into
the joint cavities aFer exercise or trauma. Hemophilias are man-
aged clinically by transfusions of fresh plasma or injections of
the appropriate puriﬁed clotting factor. Tese therapies provide
relief for several days but are expensive and inconvenient.
In addition, dependence on transfusions or injections has caused
other problems. In the past, many hemophilia patients became
Disorders of Hemostasis
Blood clotting is one of nature’s most elegant creations, but it
sometimes goes awry. Te two major disorders of hemostasis
are at opposite poles.
conditions that cause undesirable clot formation.
arise from abnormalities that prevent normal clot
Disseminated intravascular coagulation (DIC)
which has characteristics of both types of disorder, involves
both widespread clotting and severe bleeding.
Despite the body’s many safeguards, undesirable intravascular
clotting, called “hemostasis in the wrong place” by some, some-
Thrombi and Emboli
A clot that develops and persists in an
blood vessel is called a
. If the thrombus is
large enough, it may block circulation to the cells beyond the
occlusion and lead to death of those tissues. ²or example, if the
blockage occurs in the coronary circulation of the heart (coro-
nary thrombosis), the consequences may be death of heart mus-
cle and a fatal heart attack.
If the thrombus breaks away from the vessel wall and ﬂoats
freely in the bloodstream, it becomes an
). An embolus (“wedge”) is usually no problem until it en-
counters a blood vessel too narrow for it to pass through. Ten
it becomes an
, obstructing the vessel. ²or example,
emboli that become trapped in the lungs (pulmonary embo-
lisms) dangerously impair the body’s ability to obtain oxygen. A
cerebral embolism may cause a stroke.
Conditions that roughen the vessel endothelium, such as
atherosclerosis or inﬂammation, cause thromboembolic disease
by allowing platelets to gain a foothold. Slowly ﬂowing blood
or blood stasis is another risk factor, particularly in bedridden
patients and those taking a long ﬂight without moving around.
In this case, clotting factors are not washed away as usual and
accumulate, allowing clots to form.
A number of drugs—most importantly
aspirin, heparin, and warfarin—are used clinically to prevent
is an antiprostaglandin drug that
inhibits thromboxane A
formation (blocking platelet aggrega-
tion and platelet plug formation). Clinical studies of men taking
low-dose aspirin (one aspirin every two days) over several years
demonstrated a 50% reduction in incidence of heart attack.
Other medications that are prescribed as anticoagulants are
heparin (see above) and warfarin, an ingredient in rat poison.
Administered in injectable form, heparin is the anticoagulant
most used in the hospital (for preoperative and postopera-
tive heart patients and for those receiving blood transfusions).
(Coumadin) is a mainstay of outpatient
treatment to reduce the risk of stroke in those prone to atrial ﬁ-
brillation, a condition in which blood pools in the heart. Warfa-
rin works via a diﬀerent mechanism than heparin—it interferes
with the action of vitamin K in the production of some clotting
factors (see Impaired Liver ²unction below). New on the scene
, a direct inhibitor of thrombin that is a welcome
alternative to warfarin.