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

From the Guidelines

The treatment of gastrointestinal (GI) bleeding in patients with Von Willebrand's disease (VWD) requires prompt administration of desmopressin (DDAVP) or von Willebrand factor (VWF) concentrates, depending on the disease type and severity, with the most recent evidence suggesting the use of recombinant VWF (rVWF) as a potentially more effective option than plasma-derived VWF (pdVWF) in certain cases 1. For mild to moderate Type 1 VWD, desmopressin at 0.3 mcg/kg IV over 30 minutes is typically the first-line treatment, which works by releasing stored VWF from endothelial cells, as suggested by earlier guidelines 1. However, for Type 2 or Type 3 VWD, or severe Type 1, VWF concentrate (such as Humate-P, Wilate, or Alphanate) at 40-60 IU/kg IV is recommended, with dosing adjusted based on VWF:RCo levels. Some key points to consider in the treatment of GI bleeding in VWD patients include:

• The use of antifibrinolytic agents like tranexamic acid (1000-1500 mg orally or 10 mg/kg IV three times daily) to support hemostasis, particularly for mucosal bleeding.
• Supportive measures such as red blood cell transfusions if hemoglobin drops significantly, platelet transfusions if platelet function is severely compromised, and endoscopic interventions to identify and treat the bleeding source.
• The potential role of recombinant Factor VIIa in refractory cases or patients with inhibitors, although its use should be carefully considered due to the risk of thrombotic events.
• The importance of continuing factor replacement therapy until bleeding stops and healing occurs, typically 3-7 days, and monitoring for signs of thrombosis. Given the complexity and variability of VWD, treatment should be individualized based on the specific type and severity of the disease, as well as the patient's overall clinical condition, with consideration of the most recent evidence available 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 ... mucosal bleeding

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

• It is essential to monitor bleeding time and factor VIII coagulant activity during administration to ensure adequate levels are being achieved.
• The treatment is not indicated for severe classic von Willebrand’s disease (Type I) or when there is evidence of an abnormal molecular form of factor VIII antigen.

From the Research

Treatment of GI Bleeding in Patients with Von Willebrand's Disease

• GI bleeding is a significant symptom in patients with Von Willebrand's disease (VWD), particularly in those with congenital type 3, 2A, and 2B 3.
• The presence of arteriovenous malformations is often described when endoscopic examinations are performed in patients with VWD 3.
• Endoscopic examination of the GI tract is necessary to exclude ulcers and polyps or cancer as possible causes of GI bleeding in patients with VWD 3, 4.
• Prophylaxis with VWF/factor VIII concentrates is generally started after GI-bleeding events in patients with congenital VWD, but this therapy is not always successful 3.
• Iron supplementation must be prescribed to avoid chronic iron deficiency in patients with VWD and GI bleeding 3.
• Possible rescue therapies, such as high-dose statins, octreotide, thalidomide, lenalidomide, and tamoxifen, have been described in a few case reports and series, but surgery may be necessary in emergency situations or if medical treatment fails to stop bleeding 3.

Management of GI Bleeding in VWD Patients

• Angiodysplasia-related GI bleeding is often refractory to standard treatment, including replacement therapy with VWF concentrates, and continues to remain a major challenge and cause of significant morbidity in patients with VWD 4.
• Diagnosis of GI bleeding in VWD patients remains a challenge and may require multiple radiologic and endoscopic investigations 4.
• There is a need for enhanced understanding at a molecular level to identify effective therapies for GI bleeding in VWD patients 4.
• Desmopressin can be used to prevent bleeding in VWD, and its relationship with VWF activity has been quantified in a pharmacodynamic study 5.
• Peri-procedural management of VWD utilizes VWF concentrates or desmopressin to increase VWF levels, and desmopressin is safe, easily administered, and inexpensive 6.

Use of Desmopressin in VWD Patients

• Desmopressin is effective in increasing VWF levels and preventing bleeding in VWD patients, and its use has been evaluated in several studies 5, 6, 7.
• The response to desmopressin varies among VWD patients, and a consensus definition for adequate response is lacking 6.
• Desmopressin has been used as a treatment in patients with VWD, and its efficacy has been evaluated in a systematic review 7.
• Further investigation is required to determine the most effective method for managing VWD and to establish desmopressin as a standard treatment in clinical practice 7.