Hemophilia

Hemophilia
Hemophilia is an inheritable disorder of the mech-
anism of blood clotting. Depending on the degree of
the disorder present in an individual, excess bleeding
may occur only after specific, predictable events (such
as surgery, dental procedures, or trauma), or may
occur spontaneously, with no initiating event.
Suffering an occasional cut, scratch, or bruise is a
normal consequence of life. When there is damage to
the skin and a blood vessel ruptures, bleeding occurs.
The human body is then able to initiate a series of
reactions that cause the bleeding to stop. First, platelet
cells in the blood move toward and attach to the site of
the wound. The platelets are further held in place by
strands of fibrin. The formation of the strands is the
key event in a complex series of enzymatic reactions
that are still somewhat of a mystery today. Without
this cascade clotting process, people would be in dan-
ger of bleeding to death from very minor injuries.
However, the scenario described above could be
fatal for a person afflicted with hemophilia. The term
hemophiliac, coined by German physician Johann
Scho¨ nlein (1793–1864) in 1828, is made up of Greek
and Latin terms that refer to one who loves to hemor-
rhage or bleed. First described by the Islamic surgeon
Abu al-Qasim in the tenth century, this genetic disease
has existed for several hundred years and has directly
influenced history. Queen Victoria (1819–1901) had
several hemophilic sons that died before they had the
opportunity to become King of England. As early as
the nineteenth century, scientists suspected that hemo-
philia may be passed from parents to offspring, or
inherited. They also noticed that generally only males
showed the uncontrolled bleeding that is a major
symptom of the disease.
Normal blood clotting
The normal mechanism for blood clotting is a
complex series of events involving the interaction of
the injured blood vessel, blood cells called platelets,
and over 20 different proteins that also circulate in the
blood.
When a blood vessel is injured in a way to cause
bleeding, platelets collect over the injured area, and
form a temporary plug to prevent further bleeding.
This temporary plug, however, is too disorganized to
serve as a long-term solution, so a series of chemical
events result in the formation of a more reliable plug.
The final plug involves tightly woven fibers of a mate-
rial called fibrin. The production of fibrin requires the
interaction of a variety of chemicals, in particular a
series of proteins which are called clotting factors. At
least 13 different clotting factors have been identified.
The clotting cascade, as it is usually called, is the
series of events required to form the final fibrin clot.
The cascade uses a technique called amplification to
rapidly produce the proper sized fibrin clot from the
small number of molecules initially activated by the
injury.
The defect in hemophilia
In hemophilia, certain clotting factors are either
decreased in quantity, absent, or improperly formed.
Because the clotting cascade uses amplification to rap-
idly plug up a bleeding area, absence or inactivity of
just one clotting factor can greatly increase bleeding
time.
Hemophilia A is the most common type of bleed-
ing disorder, and involves decreased activity of factor
VIII. Three levels of factor VIII deficiency exist,
and are classified based on the percentage of normal
factor VIII activity present. Half of all people with
hemophilia A have severe hemophilia. This means
that their factor VIII activity level is less than 1% of
the normal level. Such individuals frequently experi-
ence spontaneous bleeding, most frequently into their
joints, skin, and muscles. Surgery or trauma can result
in life-threatening hemorrhage, and must be carefully
managed. Individuals with 1 to 5% of normal factor
VIII activity level have moderate hemophilia, and are
at risk for heavy bleeding after seemingly minor trau-
matic injury. Individuals with 5 to 40% of normal
factor VIII activity level have mild hemophilia, and
must prepare carefully for any surgery or dental
procedures.
Individuals with hemophilia B have very similar
symptoms, but the deficient factor is factor IX.
Hemophilia C is very rare, and much more mild than
hemophilias A or B; it involves factor XI.