What is the treatment for Von Willebrand disease (VWD) with gastrointestinal (GI) bleeding?

From the Guidelines

The treatment of Von Willebrand's disease (VWD) with GI bleeding requires prompt administration of desmopressin (DDAVP) and/or von Willebrand factor (VWF) concentrates, depending on the disease type and severity. For most Type 1 VWD patients with mild to moderate bleeding, desmopressin at 0.3 mcg/kg IV or subcutaneously (or 150-300 mcg intranasally) can be effective by releasing stored VWF, as suggested by the European guideline 1.

Key Considerations

• For Type 2 or Type 3 VWD, or severe GI bleeding, VWF concentrate (Humate-P, Wilate, or Alphanate) at 40-60 IU/kg IV is the first-line treatment, potentially repeated every 8-12 hours until bleeding stops.
• Adjunctive treatments include antifibrinolytics like tranexamic acid (1000-1500 mg orally three times daily or 10 mg/kg IV every 8 hours) to stabilize clots.
• Platelet transfusions may be considered for severe bleeding unresponsive to primary therapy.
• Endoscopic intervention is often necessary to identify and treat the bleeding source.
• Iron supplementation (ferrous sulfate 325 mg three times daily) should be initiated for anemia, and IV iron may be required for severe cases. These treatments work by replacing missing VWF, which is essential for platelet adhesion at injury sites and for protecting Factor VIII from degradation, thus restoring hemostasis in the GI tract, as described in the clinical and laboratory diagnosis of von Willebrand disease guidelines 1.

Disease Types and Severity

• Type 1 VWD accounts for ~75% of symptomatic persons, and nearly all the remaining affected persons have Type 2 variants, with Type 2A more common than types 2B, 2M, or 2N.
• Type 3 VWD is rare, affecting only ~1 person in 1,000. It is crucial to evaluate the patient's bleeding symptoms, history, or medical conditions associated with increased bleeding risk with invasive procedures, as recommended by the National Heart, Lung, and Blood Institute (NHLBI) guidelines 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 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

Desmopressin acetate injection may be used to treat GI bleeding in patients with mild to moderate von Willebrand's disease (Type I) with factor VIII levels greater than 5% 2.

• Key considerations:
  • The patient should have mild to moderate von Willebrand's disease (Type I).
  • The patient should have factor VIII levels greater than 5%.
  • Desmopressin acetate injection is not indicated for severe von Willebrand's disease (Type I) or when there is evidence of an abnormal molecular form of factor VIII antigen.
• Monitoring: 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.

From the Research

Treatment of Von Willebrand's Disease with GI Bleeding

• The treatment of gastrointestinal (GI) bleeding in von Willebrand disease (VWD) is challenging and requires a comprehensive approach 3, 4.
• Patients with congenital type 3, 2A, and 2B VWD are most frequently affected by GI bleeding, which can also occur in patients with acquired von Willebrand syndrome 3.
• Endoscopic examination of the GI tract is necessary to exclude ulcers, polyps, or cancer as possible causes of GI bleeding 3.
• Prophylaxis with VWF/factor VIII concentrates may be started after GI-bleeding events, but this therapy is not always successful 3.
• Iron supplementation is essential to avoid chronic iron deficiency 3.
• Possible rescue therapies, such as high-dose statins, octreotide, thalidomide, lenalidomide, and tamoxifen, have been described in case reports and series, but surgery may be necessary in emergency situations or if medical treatment fails to stop bleeding 3.

Role of Desmopressin in VWD Treatment

• Desmopressin (DDAVP) is a synthetic peptide that can induce release of normal VWF from cellular compartments and is the treatment of choice for type 1 VWD 5.
• DDAVP can also be clinically useful in other VWD types, including acquired von Willebrand syndrome (AVWS) 5.
• A test dose of DDAVP at the time of diagnosis is recommended to establish the individual patterns of biological response and to predict clinical efficacy during bleeding and surgery 5.
• The relationship between desmopressin concentration and VWF activity has been quantified in a pharmacodynamic study, which demonstrated that VWF activity increases with desmopressin plasma concentration 6.
• A systematic review of desmopressin as a treatment in patients with VWD found that it is a effective treatment option, but further investigation is required to determine the most effective method for managing VWD 7.

Management of GI Bleeding in VWD

• GI bleeding caused by angiodysplasia is overrepresented in VWD patients compared to other causes, and the bleeding from angiodysplasia is notoriously difficult to treat 4.
• The predisposition to angiodysplasia likely accounts for many of the clinical difficulties related to managing GI bleeding in VWD patients 4.
• Diagnosis and treatment of GI bleeding in VWD are challenging, and much further research is needed to optimize care for these patients with regard to acute treatment, prophylaxis, and adjunctive therapies 4.