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Von Willebrand Disease: Definition, causes, treatment – Von Willebrand Disease

Von Willebrand Disease is a condition in which the Von Willebrand factor, a protein that helps in blood clotting, is missing, leading to several complications.

Importantly, it is a condition that affects 1% of the population, approximately 125 per million people. Within this article, you will find answers to some of the most common questions like what it is, how serious it can be, and many others. Before reaching that point, there will be brief explanations about the basic concepts of the disease.

By reading this article, you will obtain critical insights about Von Willebrand Disease, its causes, its diagnosis, and its complications. Please continue reading to get pearls on this specific topic by the hand of a Doctor.

What is Von Willebrand Disease?

Von Willebrand Disease is a bleeding disorder in which the blood is not clotting properly. Blood clotting or hemostasis is a process that involves many components, including proteins and platelets. One of them is the Von Willebrand Factor.

Hemostasis has four essential steps to form a blood clot and finally close the rupture in a blood vessel. These four steps are the following:

  1. Constriction or narrowing of the blood vessel
  2. Formation of temporary “platelet plug”
  3. Activation of the coagulation cascade
  4. Creation of “fibrin plug” or the final clot

After the initial damage to the blood vessel, it constricts itself to prevent the loss of blood. Additionally, it lets out a signal (proteins that act as markers) to bring platelets to the damaged site.

These platelets begin to bind between each other to form a temporary clot to prevent blood loss. Platelets also release chemicals into the bloodstream to bring the proteins that will definitely close the injury.

These are specific proteins that receive the name of Factors. They have roman numerals by their side, for example, Factor VIII. These clotting factors will act as a link between them to activate thrombin. This latter enzyme will make a substance called fibrinogen that will then become fibrin. Finally, fibrin has a composition that will repair the injured blood vessel.

Von Willebrand factor plays a significant role in blood clotting as it promotes the platelet function. It enhances platelet adhesion to the injury’s location. Also, it helps maintain normal Factor VIII levels.

In a nutshell, without the Von Willebrand factor, Factor VIII would degrade very quickly. If Von Willebrand factor levels are low, like in Von Willebrand Disease, abnormal bleeding may happen. The response will be slower, and there will not be enough clotting factors to repair the injury.

Is Von Willebrand Disease genetic?

Yes, it is an inherited bleeding disorder, although acquired Von Willebrand disease can happen as well. Most of the cases have a genetic base.

The gene expression that codes the synthesis of the Von Willebrand Factor (VWF) is deficient or non-existent. The proteins have a particular conformation that works like a puzzle; multiple parts come together to form the protein; these parts receive the name of dimers.

When these dimers come together, they receive the name of the multimer. In the inherited VWD, the VWF multimer can be incomplete or, in some cases, inexistent as many parts of the multimer cannot be created

The gene that gives the order to the organism to create parts of the protein is defective, and it can lead to a decrease in the synthesis of the protein. This situation causes a decrease in the VWF levels.

A defective gene can also result in a defective multimer that will lead to severe bleeding. Depending on the type of defect on the gene, the disease can be mild or severe.

The most common of them are mild, but there are several types of the disease. There is an equal distribution of the disease among men and women, although it is a genetic disease.  

What are the different types of this disease?

Von Willebrand Disease or Von Willebrand syndrome has several variants. This disease can go from an inherited condition to the acquired Von Willebrand syndrome.

Each one of them has a particularity, and each one affects the body differently. Some of those presentations can be mild, while others can be severe. It consists of the following:

Von Willebrand Disease Type 1

Type 1 is the mildest form of this bleeding problem. It consists of a mild to moderate quantitative deficiency in the Von Willebrand Factor (VWF).

There is also a decrease in the quantity of Factor VIII and a reduction in the VWF antigen.

For example, the deficiency of VWF levels is about 20% to 50% of normal levels. Importantly, type 1 accounts for most of the cases of Von Willebrand Disease.

Von Willebrand Disease Type 2

Type 2 of this disease, instead of a quantitative problem, is a qualitative problem. The quality of the Von Willebrand Factor in this type is not good. It affects approximately 15% to 20% of the patients with Von Willebrand Disease.

However, there are variations within this type. This type has four subdivisions. Although they are very similar, they have key differences that will be reflected in the patient. The branches are the following:

  • Type 2A: This is the most common qualitative abnormality; there is an alteration in the Von Willebrand Factor, causing it to fail to bind to platelets. This reduces the ability of platelets to clump together to form a clot.
  • Type 2B: In this type, there is an alteration that causes the platelets to have an increased ability to clump together prematurely. They clump together in the bloodstream rather than at the site of blood vessel injury.
  • Type 2M: In type 2M, there is a decrease in the activity of the Von Willebrand Factor, and additionally, it fails to interact with the platelets. 
  • Type 2N: This type can resemble the mild form of classic Hemophilia (Hemophilia A). In this type, the Von Willebrand Factor fails to transport the Factor VIII to the site of injury. Moreover, in this type, there are low levels of Factor VIII in blood as the Von Willebrand Factor fails to bind to Factor VIII. This leads to a decrease in the lifetime of Factor VIII in the blood.

Von Willebrand Disease Type 3

In type 3, there is a severe quantitative deficiency of Von Willebrand Factor in the blood. In blood tests, there is very little or no detectable Von Willebrand Factor in this type. These patients have profound bleeding disorders. It affects approximately 5% of the patients with Von Willebrand Disease

Acquired Von Willebrand Disease

Acquired Von Willebrand Disease is a rare condition in which the body creates antibodies to the Von Willebrand Factor. Due to this specific event, it can be classified as an autoimmune disease.

It may arise from various mechanisms, including lymphoproliferative, cardiovascular, and thyroid diseases. This condition typically resolves with treatment of the cause. For example, patients with hypothyroidism can develop this condition, and it improves when treating the disease.

What medications can cause Von Willebrand disease?

Despite that it is very rare and unlikely to happen, it is a possibility. Some studies show that a few medications can lead to the development of acquired Von Willebrand disease.

Nonetheless, the most common causes for the development of acquired Von Willebrand disease are underlying conditions like leukemia, systemic lupus erythematosus, or heart problems. The following medications are described to cause Von Willebrand’s disease:

  • Ciprofloxacin
  • Griseofulvin
  • Valproic acid

What are the symptoms of Von Willebrand Disease?

Many people with Von Willebrand Disease do not know it because the signs are mild or absent. However, these patients have an increased bleeding tendency.

The most common sign of the condition is abnormal bleeding. There are three main types of the disease.

Importantly, the amount of bleeding varies from one person to another, depending on the type and severity of the disease. The significant signs of this disease are the following.

Frequent or Hard-to-stop nosebleeds

  • They are spontaneous and start without any injury.
  • Last more than 10 minutes
  • Occur often, usually five times or more in a year

Easy bruising

  • Occurs with very little or no trauma injury
  • Occurs often, approximately one to four times per month
  • It is not flat, in fact, it has a raised lump

Heavy menstrual bleeding

For women, this can be very troublesome as menstrual bleeding becomes heavier or longer and can lead to other complications.

  • Clots are larger than the size of a quarter
  • More than one pad is soaked through every 2 hours.
  • A diagnosis of anemia (not having enough red blood cells) as a result of bleeding from heavy periods

More prolonged than normal bleeding after injury, surgery, childbirth, or dental work

Mucocutaneous bleeding is one of the main bleeding symptoms of this disease. This is one of the most common causes for patients to visit the doctor. Some of the signs are the following.

  • After a cut to the skin, the bleeding lasts more than 5 minutes.
  • Heavy or more prolonged bleeding occurs after surgery.
  • Abundant bleeding occurs during or after childbirth.
  • Substantial bleeding occurs during or after dental surgery.
  • Blood in the stool from bleeding into the stomach or the bowel
  • Blood in the joints or internal organs in severe cases (Type 3)

How is Von Willebrand Disease diagnosed?

The doctor will perform a full physical examination to evaluate the patient’s condition and explore its possible cause.

A complete history takes place, as well. The doctor interrogates the patient about its condition and its familiar history.

The familiar history is significant in these cases as it is a disease that runs in families. Remember, most of the time it is a genetic condition.

Besides, the doctor will also ask for the following tests to make an assertive diagnosis.

  • Complete Blood Count: This measures the hemoglobin, the size and number of red blood cells, platelet count, among others. People with unusual and excessive bleeding can have low counts of red blood cells and hemoglobin.
  • Activated Partial Thromboplastin Time (aPTT): This test measures how long it takes for blood to clot. It measures the activity of Factors VIII, IX, XI, and XII.
  • Prothrombin Time (PT): This test also measures how long it takes for blood to clot. However, this test measures the clotting ability of the Factors I, II, V, VII, and X. 
  • Fibrinogen Test: This test also helps doctors assess a patient’s ability to form a blood clot. 
  • Von Willebrand Factor antigen: This determines the level of Von Willebrand factor in blood by measuring a particular protein.
  • Von Willebrand Factor activity: This test aims to measure how well the Von Willebrand factor works in the blood.
  • Factor VIII clotting activity: This test shows if the patient has abnormally low levels and activity of Factor VIII.
  • Von Willebrand Factor multimers: This evaluates the structure of the Von Willebrand factor in the blood. This information helps the doctor to identify the type of Von Willebrand disease the patient has.

What are the treatments for Von Willebrand Disease?

Even though the Von Willebrand disease is a condition that has no cure, treatment can help prevent or stop bleeding. Nonetheless, the treatment depends on other variables too.

For example, the type and severity of the disease, how was the response to previous therapy, and the overall history of the patient, including medications and other conditions.

The doctor can suggest one or more of the following treatments help the patient in an attempt to control the symptoms of the disease:

  1. Desmopressin: It is a synthetic hormone that controls bleeding by stimulating the body to release more Von Willebrand factor stored in the lining of the blood vessels. It is available as an injection (DDAVP) or nasal spray. Many doctors consider the DDAVP the first treatment to manage Von Willebrand disease.
  2. Replacement Therapies: These include infusions of concentrated blood-clotting factors containing Von Willebrand Factor and Factor VIII. Doctors may use this type of treatment if the DDAVP is ineffective or is not an option for the patient.
  3. Oral Contraceptives: This can be useful for women as it helps them to control heavy menstrual bleeding. The estrogen hormones can boost the Von Willebrand factor and Factor VIII activity.
  4. Clot-stabilizing medications: These are anti-fibrinolytic medications; they can help to stop bleeding by slowing the breakdown of blood clots. Doctors commonly use these medications before or after a surgical procedure. Some of these medications are aminocaproic acid (Amicar) and tranexamic acid (Cyclokaprone)
  5. Drugs applied to cuts: These are fibrin sealants that, if placed on a cut it helps curtail bleeding. There are also over-the-counter products to stop nosebleeds.

How serious is Von Willebrand Disease?

It depends on the type of the Von Willebrand disease as they can go from have very mild symptoms to severe symptoms and complications. These are patients that will have trouble with injuries due to its bleeding problem.

The most serious of the types of Von Willebrand disease is type 3, as these patients have no Von Willebrand factor. This will lead to uncontrollable and prolonged bleeding, which can be life-threatening. It can also affect joints through the body, and these patients can develop multiple hematomas (purple skin lesions). 

However, Von Willebrand disease, aside from this specific type, is not a very serious disease as it does not cause serious problems. There is currently no cure for this disease, but patients with this condition can live normal and active lives.

Furthermore, patients with this condition should visit a doctor to receive treatment and control the possible disease’s complications.

Patients with type 2B are at risk of developing thrombocytopenia, a condition in which there are not enough platelets in the bloodstream. This can be troublesome if patients are going through pregnancy or surgeries. Similarly, all of the patients with this condition are at risk too of having low red blood cell count and a decrease of hemoglobin, making them feel tired throughout the day.

Can Von Willebrand Disease cause infertility?

No, normally, women with Von Willebrand disease have no problems with fertilization. These women can get pregnant like any other woman. However, it depends on the specific type of Von Willebrand Disease, which might relate to some troubles during pregnancy.

Moreover, pregnancy is a time when bleeding problems can manifest. Fortunately, the levels of Von Willebrand factor in women with type 1 Von Willebrand disease goes up during pregnancy and at the time of childbirth.

However, after childbirth, it can get a little troublesome because the Von Willebrand factor levels fall quickly, and bleeding can continue for many weeks. Women with types 2 and 3 Von Willebrand disease can also have children, but these may need more precautions during the pregnancy.

These women should be in continuous control with an obstetrician and a hematologist to take care of the patient and the baby through the whole process. Thankfully, type 1 patients will have less bleeding than they normally do. This is because high hormone levels during pregnancy stimulate the production of blood-clotting proteins.

As a result, levels of Von Willebrand factor and Factor VIII rise closer to normal. In type 2, the levels of the Von Willebrand factor rise as well, but because it has a defective structure, the bleeding disorder will not be corrected.

Similarly, in type 3, the levels will not rise because they do not produce any Von Willebrand factor. So, women with type 3 disorder are at risk of having frequent miscarriages or spontaneous abortions

Why is PT normal in Von Willebrand Disease?

PT or Prothrombin time is a test that measures how long it takes the blood to clot. It is very similar to the activated partial thromboplastin time (aPTT), another test that measures blood clotting time.

However, while doing the initial screening of the patient with Von Willebrand disease, the results of the activated partial thromboplastin time may be abnormal, but the prothrombin time results are normal.

This situation exists because although both studies measure the velocity of blood clotting, they focus on different proteins. In Von Willebrand disease, there is a failure with the Von Willebrand factor, a protein that binds to Factor VIII.

The factor VIII is an essential component for the creation of a blood clot. If the Von Willebrand factor levels are low, the Factor VIII levels will also be below average. 

In the aPTT, the study focuses on the following proteins:

  • VIII Factor
  • IX Factor
  • XI Factor
  • XII Factor

While the PT study focuses on the following proteins:

  • I Factor
  • II Factor
  • V Factor
  • VII Factor
  • X Factor

Knowing this and how the Von Willebrand disease works, the prothrombin time results will be normal. This test does not include Factor VIII. On the other hand, this explains why there are abnormal results in the aPTT test. This test consists of Factor VIII, which levels in the blood are low because of the disease.

Is Von Willebrand Disease the same as Hemophilia?

No, although Von Willebrand disease and Hemophilia are very similar diseases, they are different. Patients in both diseases have a bleeding disorder, in which they can experience abnormal bleeding and easy bruising, among other symptoms.

Both of them are as well inherited diseases that affect proteins that induce the coagulation in injuries. The difference between both of the diseases can be found in the altered gene and its consequences.

In the Von Willebrand disease, the affection is primarily in the Von Willebrand factor. This protein helps in the binding of platelets and coagulation factors. It also binds to the Factor VIII to allow it to have a longer life in the bloodstream.

In Hemophilia, the genetic defect causes a mutation in the coagulation factors, but the Von Willebrand factor works appropriately. There are two types of Hemophilia, A, and B.

In hemophilia A, the most common type of the disease. It has mutations in the Coagulation Factor VIII, causing deficiencies. While in Hemophilia B, the mutation happens in the Coagulation Factor IX, causing deficiencies of this factor.

Hemophilia is a rare condition that has more complications and can be more severe than Von Willebrand disease. The locations of the bleedings vary between these two diseases.

In Von Willebrand disease, the target is skin and mucous membranes like mouth, bowels, and vagina. While in Hemophilia’s deficiency of Factor VIII or IX causes more bleeding in joints and within muscles as these coagulation factors are more critical in deep tissues.

Are you having symptoms of it?

This tool is a Von Willebrand Disease symptoms checker. It gathers the most important signs, symptoms, and risk factors for this disease. Therefore, it will determine for anybody who uses it the likelihood of having this condition.

The best feature of this tool is that it is free and would only take you a few minutes to complete it.

What do you think?

Written by Dr. Esteban Kosak

Doctor of Medicine - MD Recently Graduated from Medical School and inspired to aid the global population during this situation. I think that we shall no longer be waiting to see a doctor when we feel sick. Several times we feel disease searches in Google drive us to a rabbit hole and come out thinking that we may die of cancer or something very serious, given that symptoms may seem to fit a wide variety of illnesses. Since I recently graduated from medical school. I have all the medical information fresh in my mind. My thorough experience as an expert researcher allows me to very-well known the different diseases and conditions that affect human bodies. Empowered by the United Nations 17 Sustainable Development Goals (SGDs). I think that we all can provide a grain of sand to help humanity. That's why we created Symptoms.Care a place where you can come and screen your symptoms and find what different illnesses can be related to them. Armed with the right information you can instantly, discretely, secure and from the comfort of your home talk with a Doctor that can Evaluate your Symptoms and help you seek the right treatment.

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