Von Willebrand's disease

Von Willebrand's disease is a hereditary or acquired coagulation disorder characterized by a qualitative or quantitative deficiency of the von willebrand factor. Von Willebrand's factor plays an important role in platelet adhesion. Signs and symptoms include bruises, nose bleeding, gum bleeding following a dental procedure, heavy menstrual bleeding, and gastrointestinal bleeding.

Autosomal dominant inheritance

Pathophysiology

Von Willebrand disease (VWD) is a blood disorder in which the blood does not clot properly. Blood contains many proteins that help the body stop bleeding. One of these proteins is called von Willebrand factor (VWF). People with VWD either have a low level of VWF in their blood or the VWF protein doesn’t work the way it should.

Normal clotting

Normally, when a person is injured and starts to bleed, the VWF in the blood attaches to small blood cells called platelets. This helps the platelets stick together, like glue, to form a clot at the site of injury and stop the bleeding. When a person has VWD, because the VWF doesn’t work the way it should, the clot might take longer to form or not form the way it should, and bleeding might take longer to stop. This can lead to heavy, hard-to-stop bleeding. Although rare, the bleeding can be severe enough to damage joints or internal organs, or even be life-threatening.

Epidemiology

VWD is the most common bleeding disorder, found in up to 1% of the U.S. population. This means that 3.2 million (or about 1 in every 100) people in the United States have the disease. Although VWD occurs among men and women equally, women are more likely to notice the symptoms because of heavy or abnormal bleeding during their menstrual periods and after childbirth.

Types of VWD

Type 1

This is the most common and mildest form of VWD, in which a person has lower than normal levels of VWF. A person with Type 1 VWD also might have low levels of factor VIII, another type of blood-clotting protein. This should not be confused with hemophilia, in which there are low levels or a complete lack of factor VIII but normal levels of VWF. About 85% of people treated for VWD have Type 1.

2a, b, m, and n

With this type of VWD, although the body makes normal amounts of the VWF, the factor does not work the way it should. Type 2 is further broken down into four subtypes―2A, 2B, 2M, and 2N―depending on the specific problem with the person’s VWF. Because the treatment is different for each type, it is important that a person know which subtype he or she has.

Type 3

This is the most severe form of VWD, in which a person has very little or no VWF and low levels of factor VIII. This is the rarest type of VWD. Only 3% of people with VWD have Type 3.

Causes

• Most people who have VWD are born with it. It almost always is inherited, or passed down, from a parent to a child.
• VWD can be passed down from either the mother or the father, or both, to the child.
• While rare, it is possible for a person to get VWD without a family history of the disease.
• This happens when a “spontaneous mutation” occurs.
• That means there has been a change in the person’s gene.
• Whether the child received the affected gene from a parent or as a result of a mutation, once the child has it, the child can later pass it along to his or her children.
• Rarely, a person who is not born with VWD can acquire it or have it first occur later in life.
• This can happen when a person’s own immune system destroys his or her VWF, often as a result of use of a medication or as a result of another disease.
• If VWD is acquired, meaning it was not inherited from a parent, it cannot be passed along to any children.

Signs and Symptoms

• Frequent or Hard-to-Stop Nosebleeds
• People with VWD might have nosebleeds that:
• Start without injury (spontaneous)
• Occur often, usually five times or more in a year
• Last more than 10 minutes
• Need packing or cautery to stop the bleeding
• Easy Bruising
• People with VWD might experience easy bruising that:
• Occurs with very little or no trauma or injury
• Occurs often (one to four times per month)
• Is larger than the size of a quarter
• Is not flat and has a raised lump
• Heavy Menstrual Bleeding
• Women with VWD might have heavy menstrual periods during which:
• Clots larger than the size of a quarter are passed
• More than one pad is soaked through every 2 hours

Diagnosis

• To find out if a person has VWD, ask questions about personal and family histories of bleeding.
• Also check for unusual bruising or other signs of recent bleeding and order some blood tests that will measure how the blood clots.
• The tests will provide information about the amount of clotting proteins present in the blood and if the clotting proteins are working properly. Because certain medications can cause bleeding, even among people without a bleeding disorder, the doctor will ask about recent or routine medications taken that could cause bleeding or make bleeding symptoms worse.

Medical History

Your doctor will likely ask questions about your medical history and your family's medical history. He or she may ask about:

• Any bleeding from a small wound that lasted more than 15 minutes or started up again within the first 7 days following the injury.
• Any prolonged, heavy, or repeated bleeding that required medical care after surgery or dental extractions.
• Any bruising with little or no apparent trauma, especially if you could feel a lump under the bruise.
• Any nosebleeds that occurred for no known reason and lasted more than 10 minutes despite pressure on the nose, or any nosebleeds that needed medical attention.
• Any blood in your stools for no known reason.
• Any heavy menstrual bleeding (for women). This bleeding usually involves clots or lasts longer than 7 to 10 days.
• Any history of muscle or joint bleeding.
• Any medicines you've taken that might cause bleeding or increase the risk of bleeding. Examples include aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), clopidogrel, warfarin, or heparin.
• Any history of liver or kidney disease, blood or bone marrow disease, or high or low blood platelet counts.

Physical Exam

Your doctor will do a physical exam to look for unusual bruising or other signs of recent bleeding. He or she also will look for signs of liver disease or anemia (a low red blood cell count).

Diagnostic Tests

No single test can diagnose VWD. Your doctor may recommend one or more blood tests to diagnose the disorder. These tests may include:

• Von Willebrand factor antigen. This test measures the amount of von Willebrand factor in your blood.
• Von Willebrand factor ristocetin (ris-to-SEE-tin) cofactor activity. This test shows how well your von Willebrand factor works.
• Factor VIII clotting activity. This test checks the clotting activity of factor VIII. Some people who have VWD have low levels of factor VIII activity, while others have normal levels.
• Von Willebrand factor multimers. This test is done if one or more of the first three tests are abnormal. It shows the structure of your von Willebrand factor. The test helps your doctor diagnose what type of VWD you have.
• Platelet function test. This test measures how well your platelets are working.

You may have these tests more than once to confirm a diagnosis. Your doctor also may refer you to a hematologist to confirm the diagnosis and for followup care. A hematologist is a doctor who specializes in diagnosing and treating blood disorders.

Treatments - Von Willebrand's Disease

Treatment for von Willebrand disease (VWD) is based on the type of VWD you have and how severe it is. Most cases of VWD are mild, and you may need treatment only if you have surgery, tooth extraction, or an accident.

Medicines are used to:

• Increase the amount of von Willebrand factor and factor VIII released into the bloodstream
• Replace von Willebrand factor
• Prevent the breakdown of blood clots
• Control heavy menstrual bleeding in women

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Antihemophilic factor (human) (Brand name: Alphanate®) For surgical and/or invasive procedures in patients with von Willebrand Disease (VWD) in whom desmopressin is either ineffective or contraindicated. It is not indicated for patients with severe VWD (Type 3) undergoing major surgery
• Antihemophilic factor/von Willebrand factor complex (human), dried, pasteurized (Brand name: Humate-P) 1) In adult patients for treatment and prevention of bleeding in hemophilia A (classic hemophilia) and (2) in adult and pediatric patients for treatment of spontaneous and trauma-induced bleeding episodes in severe von Willebrand disease, and in mild .
• Desmopressin acetate (Brand name: Stimate) desmopressin acetate (Stimate) was approved for the treatment of patients with hemophilia A or von Willebrand's disease (type I) whose factor VIII coagulant activity level is greater than 5%.
• Recombinant von Willebrand factor (rhVWF) (Brand name: Vonvendi) approved for use in adults (age 18 and older) diagnosed with von Willebrand disease (VWD) for perioperative management of bleeding. December 2015 approved for use for on-demand treatment and control of bleeding episodes in adults diagnosed with von Willebrand disease (VWD).
• Human Plasma Coagulation Factor VIII And Human Plasma Von Willebrand Factor (Brand name: Wilate(R))Treatment of spontaneous or trauma-induced bleeding episodes in patients with severe von Willebrand disease (VWD) as well as patients with mild or moderate VWD in whom the use of desmopressin is known or suspected to be ineffective or contraindicated.

Treatments for Women

Treatments for women who have VWD with heavy menstrual bleeding include:

• Birth control pills. The hormones in these pills can increase the amount of von Willebrand factor and factor VIII in your blood. The hormones also can reduce menstrual blood loss. Birth control pills are the most recommended birth control method for women who have VWD.
• A levonorgestrel intrauterine device. This is a birth control device that contains the hormone progestin. The device is placed in the uterus (womb).
• Aminocaproic acid or tranexamic acid. These antifibrinolytic medicines can reduce bleeding by slowing the breakdown of blood clots.
• Desmopressin.

For some women who are done having children or don't want children, endometrial ablation (EN-do-ME-tre-al ab-LA-shun) is done. This procedure destroys the lining of the uterus. It has been shown to reduce menstrual blood loss in women who have VWD.

If you need a hysterectomy (HIS-ter-EK-to-me; surgical removal of the uterus) for another reason, this procedure will stop menstrual bleeding and possibly improve your quality of life. However, hysterectomy has its own risk of bleeding complications.

Living With

If you have von Willebrand disease (VWD), you can take steps to prevent bleeding and stay healthy.

For example, avoid over-the-counter medicines that can affect blood clotting, such as aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs (NSAIDs). Always check with your doctor before taking any medicines.

Tell your doctor, dentist, and pharmacist that you have VWD. Your dentist can ask your doctor whether you need medicine before dental work to reduce bleeding.

You also may want to tell other people about your condition, like your employee health nurse, gym trainer, and sports coach. Making them aware will allow them to act quickly if you have an injury.

Consider wearing a medical ID bracelet or necklace if you have a serious form of VWD (for example, type 3). In case of a serious accident or injury, the health care team treating you will know that you have VWD.

Be physically active and maintain a healthy weight. Physical activity helps keep muscles flexible. It also helps prevent damage to muscles and joints. Always stretch before exercising.

Some safe physical activities are swimming, biking, and walking. Football, hockey, wrestling, and lifting heavy weights are not safe activities if you have bleeding problems. Always check with your doctor before starting any exercise program.

Your parents, brothers and sisters, and children also may have VWD. Talk with them about your diagnosis and suggest that they get tested too.

Pregnancy and von Willebrand Disease

Pregnancy can be a challenge for women who have VWD. Blood levels of von Willebrand factor and factor VIII tend to increase during pregnancy. However, women who have VWD can have bleeding problems during delivery. They also are likely to have heavy bleeding for an extended time after delivery.

You can take steps to lower the risk of complications during pregnancy. If possible, talk with a hematologist and an obstetrician who specializes in high-risk pregnancies before you become pregnant.

A hematologist is a doctor who specializes in diagnosing and treating blood disorders. An obstetrician is a doctor who provides treatment and care for pregnant women.

Consider using a medical center that specializes in high-risk obstetrics and has a hematologist on staff for prenatal care and delivery.

Before you have any invasive procedure, such as amniocentesis (AM-ne-o-sen-TE-sis), discuss with your doctor whether you need to take steps to prevent serious blood loss.

During your third trimester, you should have blood tests to measure von Willebrand factor and factor VIII to help plan for delivery.

You also should meet with an anesthesiologist to review your choices for anesthesia (AN-es-THE-ze-ah) and to discuss taking medicine to reduce your bleeding risk. The term "anesthesia" refers to a loss of feeling and awareness. Some types of anesthesia temporarily put you to sleep, while others only numb certain areas of your body.

With these steps for safety, most women who have VWD can have successful pregnancies.

Children and von Willebrand Disease

If your child has VWD that's severe enough to cause bleeding, anyone who cares for him or her should be told about the condition.

For example, the school nurse, teacher, daycare provider, coach, or any leader of afterschool activities should know, especially if your child has severe VWD. This information will help them handle the situation if your child has an injury.

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