The Other Bleeding Disorder

The "Other".
Bleeding Disorder..

What is the most common inherited bleeding disorder, the one that affects many millions of people around the world, and up to two million in the United States?

You may be surprised to hear that it is not haemophilia. It is von Willebrand disease, a related disorder that few people have heard of, unless they have it or know someone who does.

Why is such a common illness such a secret? Perhaps because the disease is usually less severe than haemophilia, it has not generated the kind of publicity, educational efforts and support that other chronic illnesses have. In fact, it is often so mild, it is not diagnosed at all. Some people live with the disease for many years before getting an accurate diagnosis. For more severely affected patients, this lack of knowledge has caused real suffering.

Fortunately, substantial progress has been made in recent years. The von Willebrand gene has been identified and research is underway to develop gene therapy. As research continues, however, the challenge continues to educate healthcare professionals and the public about this disorder. That is the best way to assure those with von Willebrand that they will receive proper diagnoses and treatment.

The Basics of von Willebrand

Von Willebrand disease is not a type of haemophilia. Like haemophilia, von Willebrand disease does make it difficult to stop bleeding when an injury occurs. But the two disorders have different causes, different symptoms an many cases, different patterns of inheritance and different treatments.

The Blood Clotting Process

	Normal	In Haemophilia	In von Willebrand
	Bleeding starts	Bleeding starts	Bleeding starts
.Step 1	Blood vessels constrict	Blood vessels constrict	Blood vessels constrict
.Step 2	Platelet plug forms	Platelet plug forms	Incomplete platelet plug; bleeding continues
.Step 3	Fibrin clot forms; bleeding stops	Incomplete fribrin clot; bleeding continues	Incomplete or delayed fibrin clot; bleeding continues
The factor that is missing or deficient in haemophilia (factor VIII in haemophilia A; factor IX in haemophilia B) is essential to the formation of a fibrin clot, the tough threads that hold the platelet plug in place. The factor that is missing, deficient or abnormal in von Willebrand disease, von Willebrand factor, is essential to the formation of the platelet plug itself.

While haemophilia affects a person’s ability to complete the final step in blood clot formation, von Willebrand disease affects an earlier step in the clotting process (see above box -- "The Blood Clotting Process").

Platelets are tiny particles in the blood that clump together at the site of the injury to prepare for the formation of a blood clot. Von Willebrand factor causes them to bind to areas of a blood vessel that are damaged. If there is too little von Willebrand factor, or the factor is defective, platelets do not gather properly when a blood vessel is injured.

Some people with von Willebrand disease also have too little factor VIII. This happens because the von Willebrand protein serves as a carrier for factor VIII and when there is too little von Willebrand factor, factor VIII may also be reduced. In people with haemophilia A, who have little or no factor VIII, the level of von Willebrand factor is usually normal.

Unlike people with haemophilia, most people with von Willebrand disease do not usually bleed into joints and muscles. Because it is a disorder of the platelets, von Willebrand disease causes what is called mucosal bleeding, or bleeding into mucous membranes of the mouth, nose, intestine or uterus. This can lead to nose bleeds, unusually heavy menstrual bleeding and internal (gastrointestinal) bleeding. The severity of symptoms varies among people with von Willebrand disease, even among family members. Although the type of disease does not change, the severity of symptoms can change throughout a person’s life.

Types of von Willebrand Disease

Researchers have identified many variations of the disease, but most fall into the following classifications:

Type I: Most common and mildest form of von Willebrand disease. Levels of von Willebrand factor are lower than normal. Levels of factor VIII may also be reduced.

Type II: In these people, the von Willebrand factor itself has an abnormality. Depending on the abnormality, they may be classified as having Type IIA or Type IIB. In Type IIA, the level of von Willebrand factor is reduced as is the ability of platelets to clump together. In Type IIB, although the factor itself is defective, the ability of platelets to clump together is actually increased.

Type III: Severe von Willebrand disease. These people may have a total absence of von Willebrand factor and factor VIII levels are often less than 10%.

Pseudo (or platelet-type) von Willebrand disease: This disorder resembles Type IIB von Willebrand disease, but the defects appears to be in the platelets, rather than the von Willebrand factor.

An Equal Opportunity Disorder

This disease, like haemophilia, is passed down through the genes. Unlike haemophilia, however, which usually affects only males, von Willebrand disease occurs in men and women equally. A man or woman with the disease has a 50% chance of passing the gene on to his or her child (see box). Types I and II are usually inherited in what is known as a "dominant" pattern. This means that if even one parent has the gene and passes it onto a child, the child gets the disease. Whether the child has no symptoms, mild symptoms, or, less commonly, severe symptoms, he or she definitely has the disease. Regardless of the severity of the symptoms, the child can still pass the gene on to his or her own offspring.

Type III von Willebrand disease, however, is usually inherited in a "recessive" pattern. This type occurs when the child inherits the gene from both parents. Even if both parents have mild or asymptomatic disease, their children are likely to be severely affected.

These patterns of inheritance differ from that of haemophilia, which is caused by a defect in one of the "sex-linked" chromosomes. A man with haemophilia cannot pass the gene on to a son, because the abnormality is carried on the X chromosome, and a man contributes only a Y chromosome to his male offspring.

Research concerning the inheritance of von Willebrand disease is still underway to clarify a great deal of information that is not yet understood about the disease.

"Acquiring" von Willebrand Disease

Once in a while, people develop what appears to be von Willebrand disease later in life. When this occurs in those who have no family history of the disease, it is thought that they are probably producing antibodies that destroy or decrease the amount of von Willebrand factor. Some other people have "acquired" a form of the disease in association with another disorder, such as rheumatoid arthritis, systemic lupus erythematosus, kidney and certain cancers.

A Difficult Diagnosis

Despite progress in understanding this disorder, it is still sometimes difficult to diagnose. A physician may mistake its mild symptoms for those of other illnesses. For example, a woman with heavy menstrual bleeding might be advised to have a hysterectomy when the real cause of her disorder eventually proves to be von Willebrand disease. When a healtcare practitioner hears of recurrent nosebleeds, easy bruising, heavy menstrual periods, or longer than usual bleeding after such routine operations as tonsillectomy or tooth extraction, diagnostic tests should be performed to rule out the possibility of von Willebrand disease. Specific tests for von Willebrand factor must be conducted because people with a mild form of the disease may have normal results on the usual screening tests for bleeding disorders. The laboratory tests listed in the table elsewhere are considered the most useful.

Although the results of these tests can determine whether a person has von Willebrand disease, there are a few considerations that must be noted to make sure the diagnosis is correct. In certain situations, the amount of von Willebrand factor is temporarily increased; this could skew the results of laboratory tests. Examples include: newborns, people under stress (including a child who is crying), women who are pregnant or using birth control pills and individuals who have just had surgery or a blood transfusion. People who have recently taken aspirin or certain other medication can have an alteration in the function of their platelets. In these situations, laboratory tests may need to be repeated to assure the right diagnosis.

Various treatments are available for von Willebrand disease. Once a proper diagnosis has been made, the treating physician will decide whether therapy is required and, if so, will tailor the therapy to the case at hand.

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