Coagulation disorders (coagulopathies) are disruptions in the
body's ability to control blood clotting, an essential function of
the body designed to prevent blood loss. The most commonly known
coagulation disorder is
, a condition in which a critical component of blood coagulation is
missing, causing individuals to bleed for long periods of time before
clotting occurs. There are numerous other coagulation disorders stemming
from a variety of causes.
Coagulation, or clotting, is a complex process (called the coagulation
cascade) that involves 12 coagulation factors (designated by Roman
numerals as factors I through XII) found in blood plasma and several other
blood components. The factors include prothrombin, thrombin, and fibrin.
Each has a precise role in coagulation. Besides the factors, which are all
proteins, plasma (the fluid component of the blood) carries a number of
other proteins that regulate bleeding. Platelets, tiny colorless cells in
the blood, initiate contraction of damaged blood vessels so that less
blood is lost. They also help plug damaged blood vessels and work with
other constituents in plasma to accelerate blood clotting. A deficiency in
clotting factors or a disorder that affects platelet production or one of
the many steps in the entire process can disrupt clotting and severely
complicate blood loss from injury,
, surgery, and specific diseases or conditions in which bleeding can
Coagulation disorders arise from different causes and involve different
complications. Some common coagulation disorders are:
Hemophilia, or hemophilia A (factor VIII deficiency) affects about 20,000
Americans and one out of every 5000 males worldwide; Christmas disease, or
hemophilia B, is less common than hemophilia A. Von Willebrand's
disease affects both males and females and is often diagnosed in children.
Thrombocytopenia is the most common coagulation disorder. Factor XI
deficiency, or hemophilia C, afflicts one in 100,000 people and is the
second most common bleeding disorder among women; it occurs more
frequently among certain ethnic groups, with an incidence of about one in
10,000 among Ashkenazi Jews. A deficiency of factor VII, also called serum
prothrombin conversion accelerator (SPCA) deficiency, affects one in
500,000 people and is often diagnosed in newborns.
Causes and symptoms
Some coagulation disorders present symptoms such as severe bruising.
Others show no apparent symptoms but carry the threat of severe internal
Because of its hereditary nature, hemophilia A may be suspected before
symptoms occur. Some signs of hemophilia A are numerous large, deep
and painful, swollen joints caused by internal bleeding. Individuals with
hemophilia do not bleed faster, just longer. A person with mild hemophilia
may first discover the disorder with prolonged bleeding following a
surgical procedure or injury. If there is bleeding into the neck, head, or
digestive tract, or bleeding from an injury, emergency measures may be
required. Bleeding can be spontaneous, occurring with no obvious trauma.
Mild and severe hemophilia A are inherited through a complex genetic
system that passes a recessive gene on the female chromosome. Women
usually do not show signs of hemophilia but are carriers of the disease.
Each male child of the carrier has a 50 percent chance of having
hemophilia, and each female child has a 50 percent chance of passing the
Christmas disease, or hemophilia B, is also hereditary but less common
than hemophilia A. The severity of Christmas disease varies from mild to
severe, although mild cases are more common. The severity depends on the
degree of deficiency of factor IX. Hemophilia B symptoms are similar to
those of hemophilia A, including numerous, large, and deep bruises and
prolonged bleeding. The more dangerous symptoms are those that represent
possible internal bleeding, such as swelling of joints or bleeding into
internal organs upon trauma. Hemophilia most often occurs in families with
a known history of the disease, but occasionally, new cases occur in
families with no apparent history.
Disseminated intravascular coagulation (DIC) occurs when the malfunction
of clotting factors causes platelets to form clots in small blood vessels
throughout the body. This action leads to depletion of clotting factors
and platelets, which are then not available at a site of injury where
clotting is needed. When DIC occurs, the individual bleeds abnormally even
though there is no history of coagulation abnormality. Symptoms may
include minute spots of hemorrhage on the skin, and purple patches or
hematomas caused by bleeding under the skin. Bleeding may occur at a
surgical site or intravenous injection (IV) sites. Related symptoms
; seizures; shortness of breath; severe
in the back, muscles, abdomen, or chest; and, if prolonged or
uncorrected, shock and coma or death.
Not inherited and not a disease, DIC results from vascular complications
during pregnancy or delivery, surgery, overwhelming infections, acute
, liver disease, pancreatitis, trauma, snakebites, and other causes. As of
2004 it was not precisely understood why or how these various disorders
lead to uncontrolled intravascular coagulation. What the underlying causes
of DIC have in common is a dysfunction that involves proteins, platelets,
or other clotting factors and processes. For example, uterine tissue can
enter the mother's circulation during prolonged labor, introducing
foreign proteins into the blood, or the venom of some exotic snakes can
activate one of the clotting factors. Severe head trauma can expose blood
to brain tissue. Regardless of the specific cause of DIC, the results are
a malfunction of thrombin (an enzyme) and prothrombin (a glycoprotein),
which activate the fibrinolytic system, releasing clotting factors in the
blood. DIC can alternate from hemorrhage to thrombosis, and both can
exist, which further complicates diagnosis and treatment.
Thrombocytopenia may be acquired or congenital (existing at birth). It
represents a defective or decreased production of platelets. Symptoms
include sudden onset of small bruises or spots of hemorrhage on the skin
or bleeding into mucous membranes (such as nosebleeds). The disorder may
also be evident as blood in vomit or stools, bleeding during surgery, or
heavy menstrual flow.
Some patients show none of these symptoms but complain of fatigue and
general weakness. There are several causes of thrombocytopenia, which is
more commonly acquired as a result of another disorder. Common underlying
disorders include leukemia, drug toxicity, or aplastic anemia, all of
which lead to decreased or defective production of platelets in the bone
marrow. Other diseases may destroy platelets outside the marrow. These
include severe infection, disseminated intravascular coagulation, and
cirrhosis of the liver. The idiopathic form most commonly occurs in
children and is most likely the result of production of antibodies that
cause destruction of platelets in the spleen and to a lesser extent the
Von Willebrand's disease is caused by a defect in the von
Willebrand clotting factor, often accompanied by a deficiency of factor
VIII as well. It is a hereditary disorder that affects both males and
females. In rare cases, it may be acquired. Symptoms include easy
bruising, bleeding in small cuts that stops and starts, abnormal bleeding
after surgery, and abnormally heavy menstrual bleeding. Nosebleeds and
blood in the stool with a black, tarlike appearance are also signs of von
Hypoprothrombinemia is an inherited or acquired deficiency in prothrombin,
or factor II, a glycoprotein formed and stored in the liver. Prothrombin,
under the right conditions, is converted to thrombin, which activates
fibrin and begins the process of coagulation. Some individuals may show no
symptoms, and others may suffer severe hemorrhaging. Easy bruising,
profuse nosebleeds, postpartum hemorrhage, excessively prolonged or heavy
menstrual bleeding, and postsurgical hemorrhage may also result. Acquired
hypoprothrombinemia usually arises from a vitamin K deficiency caused by
liver disease, newborn hemorrhagic disease, or other causes.
Factor XI deficiency, or hemophilia C, is a bleeding disorder that occurs
among certain ethnic groups. Nearly 50 percent of individuals with this
disorder experience no symptoms, but others may notice blood in their
urine, nosebleeds, or bruising. Some factor XI deficiencies may result in
bleeding long after an injury, and some women experience prolonged
bleeding after childbirth. A deficiency of factor VII may cause varying
levels of bleeding severity in those affected. Women may experience heavy
menstrual bleeding, bleeding from the gums or nose, bleeding deep within
the skin, and episodes of bleeding into the stomach, intestines, and
urinary tract. Bleeding into the joints is rare but may also occur in some
Coagulation disorders are usually discovered when an injury or surgery
initiates bleeding and the bleeding does not stop. Any signs of prolonged
bleeding, even from a small cut, should be reported to a physician or
emergency service. Bleeding under the skin (hematoma), which looks like a
severe bruise, should also be reported and medical care sought. The sooner
bleeding is controlled the better. A diagnostic work up is indicated to
reveal any coagulopathy that exists, whether inherited or acquired.
Diagnostic blood tests are performed in the clinical laboratory, including
assays of the specific clotting factors, to help detect various
coagulation disorders. Measured parameters are compared with known normal
values to detect deficiencies or defects. Additionally, a choice of
hundreds of diagnostic tests can be ordered by the physician to identify
causative conditions, deficiencies, or diseases underlying the
coagulopathy. Physicians also complete a medical history and physical
examination. If acquired coagulation disorders are suspected, information
such as prior or current diseases and medications are important to help
determine the cause of the blood disorder. Each possible coagulopathy has
specific criteria for diagnosis, including the following:
In mild coagulopathies, treatment may involve the use of drugs that
stimulate the release of deficient clotting factors. In severe cases,
bleeding may only stop if the clotting factor that is missing is replaced
through infusion of human blood components containing concentrated amounts
of specific clotting factors. These may be prepared in the form of fresh
frozen plasma or cryoprecipitate. Cryoprecipitate was invented in 1965 to
replace the need for whole plasma transfusions, which introduced more
volume than needed and carried the threat of exposure to hepatitis or
AIDs. More sensitive testing methods have virtually eliminated this risk.
Commercial preparations of freeze-dried clotting factors have also made it
possible for people to infuse themselves as directed by their physicians.
This aspect of self-care made life easier for those with coagulation
problems; in every other respect as of 2004, bleeding or coagulation
disorders should not be self-managed. Comprehensive care addresses
children's needs by providing various types of counseling to help
deal with the psychosocial aspects of diseases such as von
Willebrand's and hemophilia.
With mild bleeding episodes in persons afflicted with hemophilia A,
infusions of a drug called desmopressin (DDAVP) may be administered.
Severe bleeding episodes require transfusions of human blood clotting
factors. Hemophiliacs are encouraged to receive physical therapy to help
damaged joints and to
such as swimming, bicycle riding, or walking, to avoid injury that may
lead to bleeding.
Christmas disease is treated similarly to hemophilia A, with a mix of
synthetic products and human blood products to provide coagulation factors
as needed. Superficial
can be cleaned and bandaged. When hemophiliac children are to receive
immunizations, parents should inform medical personnel in advance so that
bleeding problems can be avoided. These children should probably not
receive intramuscular injections.
When disseminated intravascular coagulation occurs, progression can be
rapid, and treatment is complicated by the large variety of possible
underlying causes. If at all possible, the physician first treats the
underlying disorder. If the patient is not already bleeding, this
supportive treatment may correct DIC. However, if bleeding is already
occurring, a combination of transfused blood, platelets, fresh frozen
plasma, or other blood products may be needed. Heparin, an anticoagulant,
has been controversial in treating DIC, but it is often used as a last
resort to stop hemorrhage. However, heparin has not proven useful in
treating patients with DIC resulting from heat stroke, exotic snakebites,
trauma, incompatible transfusions, and acute problems resulting from
Secondary acquired thrombocytopenia is best alleviated by treating the
underlying cause or disorder. The specific treatment may depend on the
underlying cause. Sometimes, corticosteroids or immune globulin may be
given to improve platelet production.
Von Willebrand's disease is treated by several methods to reduce
bleeding time and to replace factor VIII, which then replaces the von
Willebrand factor. This may include infusion of cryoprecipitate or fresh
frozen plasma. Desmopressin may also help raise levels of the von
Hypoprothrombinemia may be treated with concentrates of prothrombin.
Vitamin K may also be given to stimulate coagulation, and in bleeding
episodes, fresh plasma products may be transfused.
Factor XI (hemophilia C) deficiency is most often treated with plasma,
since there are no commercially available concentrates of factor XI in the
United States. Factor VII deficiency may be treated with prothrombin
complex concentrates; as of 2004 factor VII is not licensed in the United
The prognosis for individuals with mild forms of coagulation disorders is
normally good. Many people can lead normal lives and achieve normal life
expectancy. Without treatment of bleeding episodes, severe muscle and
joint pain and eventually permanent damage can occur. Any incident that
causes blood to collect in the head, neck, or digestive system can be very
serious and requires immediate attention. DIC is an emergency situation
that can be severe enough to cause stroke, coma, and death. The prognosis
depends on early intervention and treatment of the underlying condition.
Hemorrhage from a coagulation disorder, particularly into the brain or
digestive track, can prove fatal.
Inherited disorders cannot be prevented; they must be managed when
detected. Acquired bleeding disorders are caused by a variety of
conditions, some related to other diseases. There is no single prevention
method although treatment of the underlying disorder or disease may
prevent episodes of bleeding and subsequent coagulation problems. Episodes
of bleeding can be prevented by avoiding injury. People who have
hemophilia A or B and other bleeding disorders are advised to avoid
activities and contact sports that can cause severe injury.
—Substances in the blood, also known as coagulation factors, that
act in sequence to stop bleeding by triggering the formation of a clot.
Each clotting factor is designated with a Roman numeral I through XIII.
—A disorder in which blood is either too slow or too quick to
—A protein that catalyzes a biochemical reaction without changing
its own structure or function.
—Severe, massive bleeding that is difficult to control. The
bleeding may be internal or external.
—An organic acid that occurs naturally in the body and prevents
blood clots. Heparin is also made synthetically and can be given as an
—Refers to a disease or condition of unknown origin.
—The term used to describe a secondary cancer, or one that has
spread from one area of the body to another.
—The formation of a blood clot in a vein or artery that may
obstruct local blood flow or may dislodge, travel downstream, and
obstruct blood flow at a remote location. The clot or thrombus may lead
to infarction, or death of tissue, due to a blocked blood supply.
The 2002 Official Patient's Sourcebook on Hemophilia.
San Diego, CA: Icon Group International, 2002.
Berntorp, Erik, et al.
Textbook on Hemophilia.
Oxford, UK: Blackwell Publishing, 2005.
Kroll, Michael H.
Manual of Coagulation Disorders.
Oxford, UK: Blackwell Publishing, 2001
Hemophilia Care in the New Millennium.
Secaucus, NJ: Kluwer Academic Publishers, 2001.
Berkeley Heights, NJ: Enslow Publishers, 2001.
National Heart, Lung, and Blood Institute.
PO Box 30105, Bethesda, MD 20824-0105. Web site:
National Hemophilia Foundation.
116 West 32nd St., 11th Floor, New York, NY 10001. Web site: