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Von Willebrand disease

vWD

Overview

Von Willebrand disease is a bleeding disorder that slows the blood clotting process. People with this disease often experience bruising, nosebleeds, and prolonged bleeding or oozing following an injury, affer surgery, or having a tooth pulled. Affected women may have heavy menstrual bleeding. In severe cases, heavy bleeding occurs after minor injury or even in the absence of injury.

It is divided into three types. Type 1 is the mildest and most common, and type 3 is the most severe and rarest form. Type 2 (four subtypes) is intermediate in severity. Increased age, pregnancy, exercise, and stress may cause von Willebrand factor levels in the blood to rise, which can make bleeding symptoms less frequent. This disease is caused by a mutation in the VWF gene and can have different inheritance patterns. Treatment varies according to the severity of the disease and includes plasma-derived clotting factor concentrates and other medications.

Symptoms - Von Willebrand disease

The signs and symptoms depend on the type and severity of the disease. Some people have the gene for the disease but do not have bleeding symptoms.

Patients with Type 1 and Type 2 disease may have the following mild to moderate bleeding symptoms:

  • Easy bruising
  • Nosebleeds
  • Bleeding from the gums after a dental procedure
  • Heavy menstrual bleeding in women
  • Blood in their stools (from bleeding in the intestines or stomach)
  • Blood in their urine (from bleeding in the kidneys or bladder)
  • Excessive bleeding after a cut or other accident
  • Excessive bleeding after surgery.

Heavy menstrual bleeding is the most common symptom in women. If untreated, it can lead to iron deficiency and anemia. Doctors usually test for the disease in women who have heavy menstrual bleeding. Some people may only be diagnosed after an episode of prolonged bleeding after an accident or surgery.

Patients with Type 3 disease (rare and severe) are usually diagnosed in childhood. They may have:

  • Any of the symptoms listed above.
  • Severe bleeding episodes for no reason. These bleeding episodes can be life threatening without immediate treatment.
  • Bleeding into soft tissues or joints, causing severe pain and swelling. Bleeding into the joint is called hemarthrosis.

Causes - Von Willebrand disease

Von Willebrand disease is typically an inherited disease caused by mutations in the VWF gene. The VWF gene provides instructions for making a blood clotting protein called von Willebrand factor, which is important for forming blood clots and preventing further blood loss after an injury. If von Willebrand factor does not function normally or too little of the protein is available, blood clots cannot form properly.  

The majority of cases of type 1 and type 2A, as well as type 2B and type 2M, are inherited in autossomal dominant manner. VWD type 2N, type 3, and some cases of type 1 and type 2A are inherited in an autossomal recessive manner, or may occur for the first time in the affected individual (known as a de novo mutation).

Most individuals with an autosomal dominant type of VWD have an affected parent. However, some individuals are affected due to having a new (de novo) mutation in the VWF gene. If the mutation found in the affected individual cannot be detected in either parent, it is most often due to a de novo mutation but may also be due to germline mosaicim in a parent. Possible non-medical explanations which may be explored include alternate paternity or maternity (e.g., with assisted reproduction) or undisclosed adoption.

Another form of the disorder, often considered a separate condition, is called acquired von Hillenbrand syndrome (AVWS). AVWS is not caused by gene mutations. This condition is typically seen in conjunction with other disorders and usually begins in adulthood.

Prevention - Von Willebrand disease

It is important that you try to prevent bleeding and stay healthy. You should:

Avoid over-the-counter medications that can affect the clotting process:

  •  Aspirin and other drugs that contain salicylates
  •  Ibuprofen
  • Other nonsteriodal anti-inflammatory drugs (eg. diclofenac)  

Always check with your doctor before taking any medication.

Tell your doctor or dentist that you have von Willebrand disease. You can receive medication before dental work that reduces bleeding.

Wear a medical ID bracelet so that in case of serious injury or accident, the doctors caring for you will know about your disease.

Exercise regularly and maintain a healthy weight. Exercise helps keep muscles flexible and helps prevent damage to muscles and joints.

Always stretch before exercising. Some safe exercises or activities are swimming, biking, and walking. Football, hockey, wrestling, and weightlifting (heavy weights) are not safe activities if you have had bleeding problems. Always check with your doctor before starting any exercise programme.

Diagnosis - Von Willebrand disease

Von Willebrand disease is sometimes difficult to diagnose. Mild symptoms may be mistaken for other illnesses. Specific tests for the disease must be done because some people with a mild form of the disease (Type 1) may have normal results on the usual test for bleeding disorders. If you have bleeding symptoms, your doctor will order blood tests that specifically check:

  • The ability of your blood to clot
  • The level of von Willebrand factor in your blood
  • How well the von Willebrand factor works

These tests should be repeated several times in order to be sure of the diagnosis.

Severe von Willebrand disease can cause significant bleeding problems during infancy. Because of this, people with severe von Willebrand disease are usually diagnosed during the first year of life. People who have milder forms may not have significant bleeding problems and may not be diagnosed until adulthood.

Your doctor will order a combination of blood tests to diagnose the disease. These tests may include:

  • Von Willebrand factor antigen. This test measures the amount of von Willebrand factor in your blood.
  • Ristocetin (ris-too-SEE-tin) cofactor activity. This test shows how well the von Willebrand factor works.
  • Test for factor VIII clotting activity. Some people with von Willebrand disease will have low levels of factor VIII activity, while others will have normal levels.
  • Von Willebrand factor multimers. This test shows the makeup or structure of the von Willebrand factor. It helps your doctor diagnose what type of disease you have.
  • Platelet function test. This test measures how well your platelets are working.

Your doctor also will ask about your personal history or family history of prolonged bleeding.

Prognosis - Von Willebrand disease

Most people with von Willebrand disease have a mild form, which usually does not cause bleeding that is life threatening. But any bleeding that cannot be controlled can be life threatening. Rarely, people with severe forms of von Willebrand disease will need to seek immediate emergency treatment to stop life threatening bleeding.

 

 

 

Treatment - Von Willebrand disease

For patients with vWD type 1 and vWD type 2A, desmopressin (DDAVP) is recommended for use in cases of minor trauma, or in preparation for dental or minor surgical procedures. DDAVP stimulates the release of von Willebrand factor (vWF) from the Weibel Palade bodies of endothelial cells, thereby increasing the levels of vWF (as well as coagulant factor VIII) 3 to 5-fold. DDAVP is available as a preparation for intranasal administration (Stimate) and as a preparation for intravenous administration.

DDAVP is contraindicated in vWD type 2b because of the risk of aggravated thrombocytopenia and thrombotic complications. DDAVP is probably not effective in vWD type 2M and is rarely effective in vWD type 2N. It is totally ineffective in vWD type 3.

Antihemophilic factors /von Willebrand factor complex (human) available 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.

Recombinant von Willebrand factor (rhVWF) is available for patients on-demand treatment and control of bleeding episodes in adults diagnosed with von Willebrand disease (VWD).

For women with heavy menstrual bleeding, estrogen-containing oral contraceptive medications are effective in reducing the frequency and duration of the menstrual periods. Estrogen compounds available for use in the correction of menorrhagia are Ethinyl Estradiol and Levonorgestel. Administration of Ethinyl Estradiol diminishes the secretion of luteinizing hormone and follicle stimulating hormone from the pituitary, leading to stabilization of the endometrial surface of the uterus.

For patients with vWD scheduled for surgery and cases of vWD disease complicated by significant hemorrhage, human derived Factor VIII concentrates, which also contain von Willebrand factors, are available for prophylaxis and treatment. Humate P, Alphanate and Koate HP are commercially available for prophylaxis and treatment of von Willebrand disease. Monoclonally purified Factor VIII concentrates and recombinant Factor VIII concentrates contain insignificant quantity of VWF and are therefore not clinically useful.

Development of alloantibodies occur in 10-15% of patients receiving human derived medium purity Factor VIII concentrates and the risk of allergic reactions including anaphylaxis must be considered when administering these preparations. Administration of the latters is also associated with increased risk of venous thromboembolic complications.

Blood transfusions are given as needed to correct anemia and hypotension secondary to hypovolemia.

Infusion of platelet concentrates is recommended for correction of hemorrhage associated with platelet-type von Willebrand disease.

The antifibrinolytic agents Epsilon amino caproic acid and Tranexamic acid are useful adjuncts in the management of vWD complicated by clinical hemorrhage.

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