Willebrand disease, acquired

Definition

Coagulation disorders deal with disruption of the body's ability to control blood clotting. The most commonly known coagulation disorder is hemophilia, a condition in which patients bleed for long periods of time before clotting. There are other coagulation disorders with a variety of causes.

Description

Coagulation, or clotting, occurs as a complex process involving several components of the blood. Plasma, the fluid component of the blood, carries a number of proteins and coagulation factors that regulate bleeding. Platelets, small colorless fragments 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 plasma to accelerate blood clotting. A disorder affecting platelet production or one of the many steps in the entire process can disrupt clotting.

Coagulation disorders arise from different causes and produce different complications. Some common coagulation disorders are:

• Hemophilia, or Hemophilia A (Factor VIII deficiency), an inherited coagulation disorder, affects about 20,000 Americans. This genetic disorder is carried by females but most often affects males.
• Christmas disease, also known as Hemophilia B or Factor IX deficiency, is less common than Hemophilia A with similar in symptoms.
• Disseminated intravascular coagulation disorder, also known as consumption coagulopathy, occurs as a result of other diseases and conditions. This disease accelerates clotting, which can actually cause hemorrhage.
• Thrombocytopenia is the most common cause of coagulation disorder. It is characterized by a lack of circulating platelets in the blood. This disease also includes idiopathic thrombocytopenia.
• Von Willebrand's disease is a hereditary disorder with prolonged bleeding time due to a clotting factor deficiency and impaired platelet function. It is the most common hereditary coagulation disorder.
• Hypoprothrombinemia is a congenital deficiency of clotting factors that can lead to hemorrhage.
• Other coagulation disorders include Factor XI deficiency, also known as Hemophilia C, and Factor VII deficiency. Hemophilia C afflicts one in 100,000 people and is the second most common bleeding disorder among women. Factor VII is also called serum prothrombin conversion accelerator (SPCA) deficiency. One in 500,000 people may be afflicted with this disorder that is often diagnosed in newborns because of bleeding into the brain as a result of traumatic delivery.

Causes & symptoms

Some coagulation disorders present symptoms such as severe bruising. Others will show no apparent symptoms, but carry the threat of severe internal bleeding.

Hemophilia

Because of its hereditary nature, hemophilia A may be suspected before symptoms occur. Some signs of hemophilia A are numerous large, deep bruises and pain and swelling of joints caused by internal bleeding. Patients 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. If there is bleeding into the neck, head, or digestive tract, or bleeding from an injury, emergency measures may be required.

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 gene on.

Christmas disease

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 the Factor IX (clotting factor). 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 will occur in families with no apparent history.

Disseminated intravascular coagulation

The name of this disorder arises from the fact that malfunction of clotting factors cause platelets to clot in small blood vessels throughout the body. This action leads to a lack of clotting factors and platelets at a site of injury that requires clotting. Patients with disseminated intravascular coagulation (DIC) will bleed 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 in the skin. A patient may bleed from surgery or intravenous injection (IV) sites. Related symptoms include vomiting, seizures, coma, shortness of breath, shock, severe pain in the back, muscles, abdomen, or chest.

DIC is not a hereditary disorder or a common one. It is most commonly caused by complications during pregnancy or delivery, overwhelming infections, acute leukemia, metastatic cancer, extensive burns and trauma, and even snakebites. There are a number of other causes of DIC, and it is not commonly understood why or how these various disorders can lead to the coagulation problem. What the underlying causes of DIC have in common is some factor that affects 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. No matter the 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

Thrombocytopenia may be acquired or congenital. It represents a defective or decreased production of platelets. Symptoms include sudden onset of small 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 in women. 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 liver.

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 Willebrand's disease.

Hypoprothrombinemia

This disorder is a 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 patients may show no symptoms and others will suffer severe hemorrhaging. Patients may experience easy bruising, profuse nosebleeds, postpartum hemorrhage, excessively prolonged or heavy menstrual bleeding, and postsurgical hemorrhage. Hypoprothrombinemia may also be acquired rather than inherited, and usually results from a Vitamin K deficiency caused by liver diseases, newborn hemorrhagic disease, or a number of other factors.

Other coagulation disorders

Factor XI deficiency, or hemophilia C, occurs more frequently among certain ethnic groups, with an incidence of about one in 10,000 among Ashkenazi Jews. Nearly 50 percent of patients with this disorder experience no symptoms, but others may notice blood in their urine, nosebleeds, or bruising. Although joint bleeding seldom occurs, some factor XI patients will experience bleeding long after an injury occurs. Some women will experience prolonged bleeding after childbirth. Patients with factor VII deficiency vary greatly in their bleeding severity. Women may experience heavy menstrual bleeding, bleeding from the gums or nose, bleeding deep within the skin, and episodes of bleeding into the stomach, intestine, and urinary tract. Factor VII patients may also suffer bleeding into joints.

Diagnosis

Several blood tests can be used to detect various coagulation disorders. There are hundreds of different tests a doctor can order to look for indications of specific diseases. In addition to blood tests, physicians will complete a medical history and physical examination. In the case of acquired coagulation disorders, information such as prior or current diseases and medications will be important in determining the cause of the blood disorder.

• Hemohilia A will be diagnosed with laboratory tests detecting presence of clotting factor VIII, factor IX, and others, as well as the presence or absence of clotting factor inhibitors.
• Christmas disease will be checked against normal bleeding and clotting time, as well as for abnormal serum reagents in factor IX deficiency. Other tests of prothrombin time and thromboplastic generation may also be ordered.
• There is no one test or group of tests that can always make (or exclude) a diagnosis of DIC. Disseminated intravascular coagulation can be diagnosed through a number of laboratory tests which measure concentration of platelets and fibrinogen in the blood with normal counts and prolonged prothrombin time. Other supportive data include diminished levels of factors V, fibrinogen, and VIII, decreased hemoglobin, and others. Since many of the test results also indicate other disorders, the physician may have to put together several results to reach a diagnosis of DIC. Serial tests may also be recommended, because a single examine at one moment in time may not reveal the process that is occurring.
• Tests for thrombocytopenia include coagulation tests revealing a decreased platelet count, prolonged bleeding time, and other measurements. If these tests indicate that platelet destruction is causing the disorder, the physician may order bone marrow examination.
• Von Willebrand's disease will be diagnosed with the assistance of laboratory tests which show prolonged bleeding time, absent or reduced levels of factor VIII, normal platelet count, and others.
• Hypothrombinemia is diagnosed with history information and the use of tests that measure vitamin K deficiency, deficiency of prothrombin, and clotting factors V, VII, IX, and X.
• Factor XI deficiency is diagnosed most often after injury-related bleeding. Blood tests can help pinpoint factor VII deficiency.

Treatment

In mild cases, 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 donated human blood in the form of fresh frozen plasma or cryoprecipitate.

• Hemophilia A in mild episodes may require infusion of a drug called desmopressin or DDAVP. Severe bleeding episodes will require transfusions of human blood clotting factors. Hemophiliacs are encouraged to receive physical therapy to help damaged joints and to exercise in non-contact sports such as swimming, bicycle riding, or walking.
• Christmas disease patients are treated similarly to hemophilia A patients. There are commercial products and human blood products available to provide coagulation. Cryoprecipitate was invented in 1965 to replace the need for whole plasma transfusions, which introduced more volume than needed. By the 1970s, people were able to infuse themselves with freeze-dried clotting factor. Superficial wounds can be cleaned and bandaged. Parents of hemophiliac children receiving immunizations should inform the vaccination provider in advance to decrease the possibility of bleeding problems. These children should probably not receive injections which go into the muscle.
• Treatment for disseminated intravascular coagulation patients is complicated by the large variety of underlying causes of the disorder. If at all possible, the physician will first treat this underlying disorder. If the patient is not already bleeding, this supportive treatment may eliminate the DIC. However, if bleeding is occurring, the patient may need blood, platelets, fresh frozen plasma, or other blood products. Heparin has been controversial in treating DIC, but it is often used as a last resort to stop hemorrhage. Heparin has not proven useful in treating patients with DIC resulting from heat stroke, exotic snakebites, trauma, mismatched transfusions, and acute problems resulting from obstetrical complications.
• Secondary acquired thrombocytopenia is best alleviated by treating the underlying cause or disorder. The specific treatment may depend on the underlying cause. Sometimes, cortocoosterids 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 consequently will replace the Von Willebrand factor. This may include infusion of cryoprecipitate or fresh frozen plasma. Desmopressin may also help raise levels of the Von Willebrand factor.
• Hypoprothrombinemia may be treated with concentrates of prothrombin. Vitamin K may also be produced, and in bleeding episodes, the patient may receive fresh plasma products.
• Factor XI (hemophilia C) is most often treated with plasma, since there are no commercially available concentrates of factor XI in the United States. Factor VII patients may be treated with prothrombin complex concentrates. As of early 1998, factor VII concentrate was not licensed in the United States and could only be used with special permission.

Alternative treatment

This can be a very severe condition and should be managed by a practitioner of alternative medicine in conjunction with a medical doctor, not self managed. For patients known to suffer from hemophilia A or B and other bleeding disorders, avoidance of activities that can cause severe injury should be practiced. Comprehensive care addresses the whole person by helping to deal with the psychosocial aspects of the disease.

Prognosis

The prognosis for patients with mild forms of coagulation disorders is normally good. Many people can lead a normal life and maintain a normal life expectancy. Without treatment of bleeding episodes, severe muscle and joint pain, and eventually, 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 can be severe enough to cause clots to form and a stroke could occur. DIC is also serious enough to cause gangrene in the fingers, nose or genitals. 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. In the past, patients who received regular transfusions of human blood products were subject to increased risk of AIDS and other diseases. However, efforts have been made since the early 1990s to ensure the safety of the blood supply.

Prevention

Prevention of coagulation disorders varies. Acquired disorders may only be prevented by preventing onset of the underlying disorder (such as cirrhosis). Hereditary disorders can be predicted with prenatal testing and genetic counseling. Prevention of severe bleeding episodes may be accomplished by refraining from activities that could cause injury, such as contact sports. Open communication with healthcare providers prior to procedures or tests that could cause bleeding may prevent a severe bleeding incident.

Key Terms

Clotting factor

Also known as coagulation factors. Proteins in the plasma which serve to activate various parts of the blood clotting process by being transformed from inactive to active form.

Enzyme

A substance that causes a chemical reaction, usually a protein. Enzymes are secreted by cells.

Hemorrhage

Abnormal bleeding from the blood vessels.

Heparin

An anticoagulant, or blood clot "dissolver."

Idiopathic

Refers to a disease of unknown cause, and sometime to a primary disease.

Metastatic

The term used to describe a secondary cancer, or one that has spread from one area of the body to another.

Serum reagents

Serum is fluid, or the fluid portion of the blood retained after removal of the blood cells and fibrin clot. Reagents are substances added to the serum to produce a chemical reaction.

Thrombosis

Formation of a clot in the blood that either blocks, or partially blocks a blood vessel. The thrombus may lead to infarction, or death of tissue due to a blocked blood supply.

Gale Encyclopedia of Medicine. Gale Research, 1999.