What is the diagnosis and treatment for Von Willebrand (vWD) factor deficiency?

From the Guidelines

Von Willebrand disease (VWD) should be diagnosed and treated based on the type and severity of the disease, with desmopressin (DDAVP) as the first-line treatment for minor bleeding or before minor procedures, and VWF concentrate replacement therapy for more severe cases. The diagnosis of VWD involves identifying the deficiency or dysfunction of von Willebrand factor (VWF), a protein that helps blood clot, and classifying it into one of the three main types: Type 1 (partial quantitative deficiency), Type 2 (qualitative deficiency), and Type 3 (virtually complete quantitative deficiency) 1. Key considerations in the treatment of VWD include:

• Using desmopressin (DDAVP) as a nasal spray (150-300 mcg) or intravenously (0.3 mcg/kg) to release stored VWF from blood vessel walls 1
• Administering VWF concentrate replacement therapy (such as Humate-P, Wilate, or Alphanate) at a dose of 40-60 IU/kg for more severe cases or when DDAVP is ineffective
• Utilizing antifibrinolytic medications like tranexamic acid (1000-1300 mg orally three times daily) or epsilon-aminocaproic acid to stabilize clots
• Considering hormonal therapies like combined oral contraceptives for women with heavy menstrual bleeding
• Avoiding aspirin and other NSAIDs that affect platelet function
• Providing genetic counseling for affected individuals and their families, as VWD is inherited in an autosomal dominant or recessive pattern depending on the type 1.

From the FDA Drug Label

Desmopressin acetate injection 4 mcg/mL is indicated for patients with mild to moderate classic von Willebrand’s disease (Type I) with factor VIII levels greater than 5% Desmopressin acetate injection will often maintain hemostasis in patients with mild to moderate von Willebrand’s disease during surgical procedures and postoperatively when administered 30 minutes prior to the scheduled procedure Desmopressin acetate injection will usually stop bleeding in mild to moderate von Willebrand’s patients with episodes of spontaneous or trauma-induced injuries such as hemarthroses, intramuscular hematomas or mucosal bleeding Those von Willebrand’s disease patients who are least likely to respond are those with severe homozygous von Willebrand’s disease with factor VIII coagulant activity and factor VIII von Willebrand factor antigen levels less than 1%. Bleeding time and factor VIII coagulant activity, ristocetin cofactor activity, and von Willebrand factor antigen should be checked during administration of desmopressin acetate injection to ensure that adequate levels are being achieved

The diagnosis of Von Willebrand disease (vWD) involves checking:

• Bleeding time
• Factor VIII coagulant activity
• Ristocetin cofactor activity
• Von Willebrand factor antigen The treatment for mild to moderate classic von Willebrand’s disease (Type I) with factor VIII levels greater than 5% is desmopressin acetate injection to maintain hemostasis during surgical procedures and postoperatively, and to stop bleeding in episodes of spontaneous or trauma-induced injuries 2.

From the Research

Diagnosis of Von Willebrand Disease

• The diagnosis of Von Willebrand disease (vWD) is based on the deficiency or abnormal activity of von Willebrand factor (VWF), a multi-adhesive protein that binds platelets to exposed subendothelium and carries factor VIII in circulation 3.
• Clinical symptoms of vWD are characterized by mucous membrane and soft tissue bleeding, bleeding after surgery, and rarely joint and gastrointestinal bleeding 3.
• Three types of the disorder have been identified: type 1 (partial VWF quantitative deficiency), type 2 (variable abnormality of VWF structure), and type 3 (severe VWF quantitative deficiency) 3.

Treatment of Von Willebrand Disease

• The aim of treatment is to correct the dual defect of hemostasis caused by the abnormal/reduced VWF and the concomitant deficiency of factor VIII 4.
• Desmopressin is the treatment of choice for type 1 vWD patients with factor VIII and VWF levels of 10 U/dL or over who have proved responsive to a test-infusion with the compound 3, 4.
• Von Willebrand factor/factor VIII concentrates are needed when desmopressin is ineffective (mainly type 2 and 3 vWD) or when correction is required for an extended time (e.g., major surgery) 3, 5.
• Dosing of VWF/FVIII concentrates can be calculated based on the FVIII content of the products or based on VWF functional activity (e.g., VWF ristocetin cofactor activity) 5.
• Pharmacokinetic-guided dosing of desmopressin and VWF-containing concentrates is being studied as a potential approach to improve treatment outcomes 6.

Management of Von Willebrand Disease

• A test dose of desmopressin at the time of diagnosis is recommended to establish the individual patterns of biological response and to predict clinical efficacy during bleeding and surgery 7.
• Laboratory monitoring of efficacy and safety issues, such as thrombosis risk and thromboprophylaxis, is important when using VWF-containing concentrates 5.
• Treatment strategies should be individualized based on the severity of the disease, the type of vWD, and the patient's response to treatment 3, 4.