• von Willebrand's disease (vWD) is the most common inherited bleeding disorder; it can result from either defective or low levels of von Willebrand factor (vWf)
• vWF:
  • Is an adhesive glycoprotein
  • Functions in primary (platelet adhesion) and secondary (clot formation) hemostasis
  • Serves as a stabilizer for Factor VIII, another protein in the coagulation cascade
• There are 3 major types of disease with type-specific morbidity, mortality, and treatments: See classification below for details

• vWD is the result of a gene mutation on chromosome 12
• Type 1: Autosomal dominant disorder with variable penetrance
• Type 2: Autosomal dominant or recessive
• Type 3: Homozygous for severe form, heterozygotes may have a less severe form
• Blood type O: Regardless of vWD, in the general population, patients with type O blood can have a 25–30% decreased level of vWf, likely secondary to increased clearance.

• vWf is produced and stored in megakaryocytes and endothelial cells (when injured, it exposes vWf and helps begin the clotting, immediately).
• Primary hemostasis: vWf binds to the platelet's surface receptor glycoprotein Ib and activates it. The ‘activated’ platelet will:
  • Adhere and aggregate to other platelets
  • Adhere to the vessel wall
• Secondary hemostasis: vWf binds Factor VIII and chaperones it to sites of vascular injury; it also stabilizes and increases Factor VIII's half-life
• Thus, defective or low levels of vWf lead to increased bleeding risk, secondary to impaired platelet adhesion and coagulation

• Determine the need for pre-treatment of vWD and/or blood transfusion for increased bleeding risk during surgery or peripartum
• Hematology consultation may be useful in cases of recent diagnosis or prolonged major surgery and should be performed weeks prior, if possible. Patients with severe disease are often under the care of a hematologist
• Careful assessment of the severity of vWD should be performed prior to employing a regional technique

• Mild–moderate: Easy bruising, epistaxis, gum bleeding, menorrhagia, melena/hematochezia, hematuria
• Severe: Hemarthrosis, spontaneous uncontrolled bleeding

Cryoprecipitate (CPT) may be used to manage acute bleeding. Fresh frozen plasma (FFP) can also be used but large volumes may be required to achieve hemostasis

• Desmopressin (DDAVP): First-line therapy for Types 1 and 2A: 0.3 mcg/kg IV in 30–50 mL NS over 30 minutes or nasal spray; stimulates endothelial cell release of vWf (also increases Factor VIII by unknown mechanism). May be re-dosed every 12–24 hours as needed, but tachyphylaxis can occur.
  • Cardiovascular disease may contraindicate its use
  • Safe in pregnancy, as it does not significantly cross the placenta.
  • Do not administer to children aged <2 years
  • Has been traditionally contraindicated in Type 2B due to DDAVP-induced thrombocytopenia; however, there have been reported cases of its clinical benefit. A test dose with platelet monitoring should be performed prior to surgery
• vWf replacement therapy: Second-line for Types 1–2; may be considered first-line for Types 2–3 as these may not respond to DDAVP. Typically in the form of Factor VIII concentrates with vWf in varying amounts (i.e., Haemate-P, Alphanate, BPL8Y). VHP-VWF is a vWf concentrate available only in France
• IVIG: Third-line therapy (1 g/kg × 2 days) for inherited disease, but may also be used for acquired vWD
• Antifibrinolytics (e.g., aminocaproic acid or tranexamic acid) may be considered
• Fibrin glue on the surgical field may be helpful
• Treatment for menorrhagia: Combined oral contraceptives, levonorgestrel intrauterine device

• Minor bleeding: Delay surgery for 1–5 days after hemostasis
• Major bleeding: Delay 7–14 days after hemostasis

• Type 1: Low levels of vWf; mildest form of disease
• Type 2: Defective and low levels of vWf
  • Type 2A (most common) demonstrates abnormal, high molecular weight multimer complexes that are responsible for platelet binding (qualitative), decreased levels of vWF (quantitative), as well as decreased levels of Factor VIII
  • Type 2B demonstrates a decrease in high molecular weight multimer complexes (qualitative) with a resultant increase in affinity for platelet glycoprotein Ib, as well as intermittent thrombocytopenia
• Type 3: No vWf, low levels of Factor VIII (most serious, rare)
• Acquired: Associated with cardiac valvular diseases, angiodysplasia, thrombocytosis, hypothyroidism

Determined by fluid shifts during procedure

• Hematology consult may be appropriate, especially in patients with vWD Type 3
• Careful monitoring of CBC, coagulation, vWf:RCo and Factor VIII; electrolytes if using DDAVP
• Medication adverse effects

• DDAVP may be associated with hypotension, hyponatremia, and increased risk of myocardial infarction in patients with coronary artery disease
• Excessive transfusion of Factor VIII has been associated with thromboembolism
• Transfusion-related risk: Infection, immune-mediated

• Cryoprecipitate
• Fresh Frozen Plasma
• Thrombocytopenia

286.4 Von Willebrand's disease

D68.0 Von Willebrand's disease

Annie D. Lee , MD

Judith A. Turner , MD, PhD