Description

• An inherited bleeding disorder caused by either a quantitative or qualitative defect of the von Willebrand protein
• Characterized by mucocutaneous bleeding or bleeding after surgical procedures

Epidemiology

Risk Factors

General Prevention

• Avoid contact sports.
• For patients with recurrent epistaxis, measures should be taken to avoid drying of the mucosa by applying petroleum jelly, humidifying the air, and reducing trauma to the nasal mucosa by keeping the fingernails short and discouraging nose picking.
• It may be advisable for patients to wear an emergency ID bracelet indicating that they have von Willebrand disease in the event they are involved in an accident that renders them unconscious.
• Avoid medications that negatively affect platelet function (i.e., ibuprofen, aspirin).
• Combination oral contraceptive pills are very effective for some patients with menorrhagia.
• Appropriate hemostatic therapy is needed prior to dental or surgical procedures to prevent bleeding.

Pathophysiology

• von Willebrand factor is a large multimeric protein that allows platelets to adhere to sites of endothelial injury, initiating the primary step in hemostasis—formation of the platelet plug.
• von Willebrand factor also serves as a carrier for factor VIII in the peripheral circulation, protecting it from degradation. Deficiency of von Willebrand factor results in a shorter factor VIII half-life, causing a lower level of circulating factor VIII.
• When von Willebrand factor is either deficient or defective, primary hemostasis is compromised, resulting in a bleeding diathesis characterized by easy bruising, frequent epistaxis, menorrhagia, and prolonged bleeding following surgical or dental procedures.
• Acquired forms of von Willebrand disease have been described in association with hypothyroidism, Wilms tumor, other neoplasms, cardiovascular disorders with increased shear stress (aortic stenosis), myeloproliferative disorders, uremia, and medications, including ciprofloxacin, griseofulvin, and valproate therapy.
• Classification: There are three major categories of von Willebrand disease:
  • Type 1
    • Mild to moderate quantitative deficiency
    • The most common type, accounting for 70–80% of patients
    • Generally a mild bleeding disorder
  • Type 2
    • Qualitative deficiency of von Willebrand factor
    • Diagnosed in 15–20% of patients
    • Tend to have more significant bleeding symptoms than in type 1
    • Type 2 von Willebrand disease is further classified into four subtypes.
      • Type 2A: loss of the intermediate- and high-molecular-weight multimers. The loss is secondary to either abnormal assembly or secretion of multimers or increased proteolytic degradation. The multimer deficiency results in decreased platelet binding.
      • Type 2B: an abnormal von Willebrand factor that spontaneously binds to normal platelets, resulting in accelerated clearance of these platelets and loss of high-molecular-weight multimers. This can result in mild thrombocytopenia.
      • Type 2N: The abnormal von Willebrand factor does not bind factor VIII optimally. This decrease in binding results in a shorter plasma half-life of factor VIII, resulting in reduced plasma factor VIII levels. Type 2N can be confused with mild hemophilia.
      • Type 2M: The abnormal von Willebrand factor fails to bind normally to platelets; normal multimers
  • Type 3
    • Near-complete quantitative deficiency of von Willebrand factor, which also results in a secondary deficiency of factor VIII
    • Accounts for <5% of patients and results in a severe bleeding disorder