von Willebrand Disease (Bleeding Disorder)

There are several processes that ensure that blood loss is stopped when a blood vessel is torn or ruptured. A platelet plug quickly reduces and even stops the blood loss and is then further secured by a blood clot which is more long lasting measure. In order for the body to carry out these functions, it needs a number of different chemicals and components in the blood to first form the platelet plug and then the blood clot. One of the important components involved in this process is von Willebrand factor (vWF). Unlike clotting factors, von Willebrand factor is not an enzyme and does not activate successive clotting factors in the coagulation process. Nevertheless it plays an integral role in blood coagulation by acting as a carrier for certain clotting factors and allowing different components to bind together to form a clot.

What is von Willebrand Disease?

von Willebrand disease (vWD) is a mild bleeding disorder caused by a deficiency or malfunctioning of von Willebrand factor (vWF). It is a fairly common inherited bleeding disorder that affects both males and females equally unlike hemophilia A and B that affects mainly males.

von Willebrand factor is a complex chemical with different compounds (multimers) to carry out it various functions. It is produced by endothelial cells and megakaryocytes and can be found in bloodstream and lining of the blood vessel.

When von Willebrand factor is deficient or defective, platelets cannot adhere to the lining of the damaged blood vessel. This disrupts the formation of a platelet plug which is an important phase in hemostastis (mechanism to prevent blood loss) which precedes the formation of a blood clot. In addition, von Willebrand factor is the protein carrier of the clotting factor VIII (inactive form) in the bloodstream. Factor VIII is activated by thrombin and works with factor IX and calcium to activate factor X as explained in the coagulation cascade. If factor VIII is not bound to von Willebrand factor, it is quickly degraded and there will be a deficiency of this clotting factor. Ultimately this affects the intrinsic pathway of the coagulation cascade.

Types of von Willebrand Disease

There are three types of von Willebrand disease – type 1, 2 and 3.

Type 1 is the most common and in there is a partial quantitative deficiency in von Willebrand factor (vWF). This means that vWF is functioning normally but there is an insufficient quantity in the bloodstream, usually between 25% to 50% lower than normal.

Type 2 is categorized into several different subtypes. In this type of von Willebrand disease, the quantity of vWF may be normal but the factor may be defective. The subtypes indicate a defect of specific portion of the chemical where binding occurs (multimer).

• Type 2A is the most common subtype with mutations in platelet binding.
• Type 2B is where there is a mutation of the platelet glycoprotein 1b (Gp1b) binding site.
• Type 2N is where there is a mutation in the factor VIII binding site.
• Type 2M is where there is abnormalities in platelet binding.

Type 3 is a severe deficiency (quantitative) in von Willebrand factor. It leads to a severe bleeding disorder but is rarely seen.

Causes of von Willebrand Disease

von Willebrand disease is a genetic disorder that is inherited and therefore present from birth. The abnormality of the gene that codes for von Willebrand disease is located on chromosome 12. It may be autosomal dominant (types 1, 2A, 2B, 2M), autosomal recessive (type 2N) or compound heterozygosity (type 3). Typically there is a family history of a bleeding disorder involving at least one parent.

Acquired von Willebrand disease or von Willebrand syndrome is not due to any genetic defect affecting the gene that codes for vWF. Instead the disease arises as a result of one or more of the following :

• antibody against vWF
• degradation of vWF
• absorption of vWF by malignant cells or activated platelet

This is seen with Wilm’s tumor, multiple myeloma, systemic lupus erythematosus (SLE) and leukemia.

Signs and Symptoms

As with other bleeding disorders, there is prolonged bleeding with even minor cuts. Most cases of von Willebrand disease is mild and can even remain unnoticed until there is major surgical or even dental procedure.

• Easy bruising
• Nosebleeds
• Bleeding gums
• Heavy or prolonged menses
• Blood in the stool
• Blood in the urine
• Hematomas (collection of blood under skin) that may cause a lump.
• Women with von Willebrand disease are more likely to suffer with anemia with additional symptoms like breathlessness and fatigue.

Sometimes the signs and symptoms of von Willebrand disease may completely disappear. This can occur when the body produces more von Willebrand factor in certain situations like during pregnancy, use of oral contaceptives, stress and infections. The symptoms usually return a short while afterwards.

Treatment of von Willebrand Disease

Treatment is not necessary in most cases since the disease is so mild. Although there is prolonged bleeding, clotting and subsequently cessation of bleeding will eventually occur.

• Desmopressin (DDAVP)  is usually administered via a nasal spray. Parenteral administration (injections) may only be necessary in severe cases but has limited benefit in type 3 vWD.
• Infusions of factor VIII or von Willebrand factor (vWF) may be considered in patients who do not respond to DDAVP or type 3 vWD.
• Anti-fibrinolytic agents delays the breakdown of blood clots.