Von Willebrand Disease

What is Von Willebrand Disease?

Von Willebrand disease (vWD) is the most prevalent congenital coagulation abnormality that is observed in human beings, although an individual can also acquire the disorder from other medical conditions. It develops from a quantitative or qualitative deficiency of the von Willebrand factor or vWF, which is a multimeric protein needed for platelet adhesion. Absence or malfunctioning of this protein makes it difficult for the blood to clot properly, which leads to incessant bleeding.

The disease affects mostly humans and dogs, especially Doberman Pinschers. In some rare cases, however, it is also seen in cats, horses, cattle and pigs.

Von Willebrand Disease History

The condition derives its name from Erik Adolf von Willebrand, the Finnish pediatrician who described this disease for the first time in the year 1926.

Von Willebrand Disease Epidemiology

As per statistics, the disease has a prevalence record of about one in per 100 individuals. Most cases of vWD are asymptomatic. Prevalence of clinically important cases is 1 in per 10000 people. More apparent or severe forms of this disorder are seen in people having blood type O.

Von Willebrand Disease Classification

Most cases of vWD are hereditary; however acquired forms of von Willebrand Disease do exist as well. The International Society on Thrombosis and Haemostasis (ISTH) classifies Von Willebrand Disease depending on the standards of quantitative and qualitative defects. The 4 hereditary types of vWD, as described by the physicians, are termed as:

Type I

It can be defined as a quantitative defect that is said to be heterozygous for that defective gene. Production of vWF is decreased in these cases. Decreased vWF levels are detected at 10 to 45% of the normal amounts, i.e. 10-45 IU.

Several instances of the Type I form are asymptomatic or can be exhibited by only mild symptoms that indicate lack of clearly impaired clotting; this might point to a bleeding disorder. Diagnosis of these cases might be difficult due to their asymptomatic character and even when it is discovered, it is done so accidentally while conducting a blood work for some other medical conditions. A lot of people lead a normal and uncomplicated life, never realizing that they have the disease.

Surgeries such as dental procedures may cause complications, like:

  • Bleeding
  • Easy bruising
  • Menorrhagia

Some minor instances of Type I vWD may also be manifested by critical hemorrhagic symptoms. Type I comprises of 60 to 80% of all the cases of vWD.

Type II

It is a qualitative malfunction and the bleeding tendencies can vary between individual patients. Normal vWF levels can be seen, but the structures of the multimers are generally abnormal. Subgroups of small or large multimers are also absent. The Type II covers 20% to 30% of all the vWD cases. Four sub-types of Type II exist; namely, the 2A, the 2B, the 2M and the 2N.

Type III

The Type III is the most intense form of the disease that is marked by a complete absence of vWF production. vWD is homozygous in case of the defective gene. The vWF is not detectable in vWF antigen assay. The vWF protects the coagulation Factor VIII from any proteolytic degradation. Due to this, the total lack of vWF results in extremely low levels of Factor VIII, much like in severe cases of hemophilia A with clinical manifestations including internal and external hemorrhages. Von Willebrand Disease Type III is inherited in an autosomal recessive pattern and hemophilia A has an x-linked recessive inheritance pattern.

Pseudo or Platelet-type vWD

The platelet-type vWD can be defined as an autosomal dominant disorder of the platelets. Qualitatively normal vWF is seen in these cases; with genetic testing of von Willebrand gene as well as the vWF protein does not reveal any mutational alteration. The problem lies with the qualitatively altered GP1 (glycoprotein1) receptor on platelet membrane that increases its tendencies to bind with the vWF.

Von Willebrand Disease Causes

This disorder is caused by deficiency of the von Willebrand Factor. The vWF is a protein that helps in clumping together of the blood platelets and then sticking to blood vessel wall. This is important for healthy blood clotting. Lack or absence of this protein interferes with the healthy blood clotting process. The additional substance of Factor VIII that is carried by the vWF also helps in stimulation of clotting. People suffering from this disease also have low levels of Factor VIII.

Von Willebrand Disease Symptoms

Many vWD patients might not experience any signs or maybe only mild symptoms. Intensity of the signs may vary from person to person in symptomatic cases. It is often difficult to diagnose vWD in milder cases. The most common symptom of this condition is abnormal bleeding, which may be present moderately or intensely. The various instances in which abnormal bleeding can occur include the following:

  • Bleeding of the gums
  • Increased menstrual flow
  • Blood in the urine or stool
  • Prolonged and recurrent nosebleeds
  • Bleeding episode experienced after shaving with razor
  • Excessive bleeding, following various dental procedures such as tooth extraction

vWD patients may even experience easy bruising and bruising accompanied by formation of lumps underneath the skin. Some individuals may have this condition after a serious trauma that causes excessive bleeding or a surgical procedure.

Symptoms of von Willebrand Disease in women

In most cases, heavy periods of menstrual bleeding are the only sign of this condition in women. However, several women suffering from this disorder go undiagnosed as they are not too concerned about their heavy menstrual bleeding for a prolonged period of time. Doctors may also overlook signs of menstrual bleeding as a possible indicator of this condition.

The various symptoms of abnormal menstrual periods include the following:

  • Menstrual bleeding lasting longer than a week
  • Anemic symptoms; such fatigue, tiredness or lack of breath
  • Having to use additional sanitary protection for controlling menstrual flow
  • Having to change tampons or menstrual pads more frequently than normal
  • Formation of menstrual blood clots that have a diameter greater than 2.5 centimeters (1 inch)
  • Loss of blood during childbirth

Von Willebrand Disease Diagnosis

Generally, vWD is somewhat difficult to diagnose. Low levels of von Willebrand Factor accompanied by bleeding is not conclusive enough to suggest presence of this disorder. The doctor will generally begin by inquiring about the patient’s complete medical history as well as check if there are any past bleeding episodes. Genetic links relating to the disease will also be checked to find out whether the patient’s siblings or parents have had any bleeding problems. A doctor would also check if there are any bruises or signs that might suggest recent bleeding episodes.

Blood tests

A number of blood tests are conducted to diagnose this disease. Results of the tests can fluctuate for the same person with time. This can be due to several factors like stress, recent surgery, blood transfusions, excessive exercise and pregnancy. A particular test may be required to be carried out for more than once. The various types of blood tests that are associated with the diagnosis of vWD include

  • Blood typing
  • Bleeding time
  • Platelet count
  • Factor VIII level
  • Platelet function test
  • Ristocetin cofactor test
  • Tests of vWF multimers
  • Platelet aggregation test
  • Von Willebrand Factor antigen

In case vWD is present, a doctor might suggest similar tests for the rest of the family members to see if the condition runs in the family.

Von Willebrand Disease Differential Diagnosis

A number of health conditions might show symptoms that are similar to that of vWD. The differential diagnosis of von Willebrand Disease include disorders such as

  • Factor X
  • Hemophilia B
  • Hemophilia A
  • Acquired vWD
  • Fibrinolytic defects
  • Factor XI Deficiency
  • Platelet function defects
  • Bernard-Soulier syndrome
  • Antiplatelet drug ingestion
  • Platelet-type vWD or pseudo vWD

Von Willebrand Disease Treatment

Although vWD can be categorized as a lifelong disorder that has no cure, this condition can be effectively treated with medications. The treatment procedure may vary based on the type that has affected the patient and its severity. It can also depend on the patient’s response to any previous therapeutic sessions. One of the most common methods of treatment includes administration of DDAVP (Desmopressin or desamino-8-arginine vasopressin). This medication is generally injected into the veins or given using a nasal spray known as Stimate. DDAVP is a synthetic hormone that is similar to vasopressin, a natural hormone that stimulates releasing of vWF and factor VIII levels. The medication is mostly effective in people having type 1 vWD and some sub-types of type 2.

Several doctors consider DDAVP medication to be the first-line treatment for the management of vWD. Some women make the use of nasal sprays during the beginning periods of their menstrual cycles in order to stop excessive bleeding. DDAVP can also be used before minor surgical procedures.

Replacement therapies are another way of treating this condition. These involve injecting prepared quantities of concentrated blood clotting factors having vWF and factor VIII in the patients’ bodies.

Clot-stabilizing or anti-fibrinolytic medications like aminocaproic acid (Amicar) or tranexamic acid (Cyklokapron) helps in slowing down the clotting factors breakdown. This helps to keep a clot in its place after it has formed thus putting an end to bleeding. These drugs are frequently prescribed after or before a tooth extraction or surgical procedure.

The drug Alphanate is an antihemophilic factor that reduces bleeding in vWD patients who must undergo surgery or other invasive procedures.

Contraceptive medications can be used for stopping heavy bleeding during menstrual periods. Bleeding can also be stopped by using fibrin sealants.

Hemorrhage tendencies associated with platelet-type vWD can be treated by infusing platelet concentrates.

Blood transfusions can help in curing anemia and hypotension that is secondary to hypovolemia.

If a patient’s health conditions are mild, the doctor might opt for treatment only during traumatic events, dental extractions or surgery.

Von Willebrand Disease Complications

vWD can lead to certain health complications, which may include:

  • Bleeding, after surgery or a dental procedure
  • Taking aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) can make vWD worse, and so these medications should not be taken without the approval of a doctor or nurse
  • Anemia, which can occur in heavily menstruating women due to iron deficiency
  • Severe pain and swelling, which can occur if abnormal bleeding takes place in the soft tissues or joints

If abnormal bleeding continues, it can be life-threatening for the patient and hence requires immediate medical attention.

Von Willebrand Disease Prognosis

Bleeding tendencies might get reduced during pregnancies. Women having this condition generally do not experience excessive bleeding at the time of childbirth.

Von Willebrand Disease Prevention

The disease normally runs down in the families. Genetic counseling can help the prospective parents to understand the risk that their children may face.

Von Willebrand Disease in Dogs

vWD is also known to affect several species of dogs, including the Doberman pinscher.

Although there are no permanent cures for vWD, doctors in most cases are able to treat this condition with appropriate medications. Genetic counseling can help couples who are eager to have children to understand the possibilities of future complications, if any.











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