What is Type 1 von Willebrand's (vWD) disease?

From the Guidelines

Von Willebrand disease type 1 is a bleeding disorder characterized by a partial quantitative deficiency of von Willebrand factor (VWF), with patients typically having reduced levels of VWF, ranging from 20-50% of normal, and experiencing mild to moderate bleeding symptoms. This condition is the most common form of von Willebrand disease, accounting for approximately 75% of symptomatic cases, as noted in the 2008 NHLBI/NIH guidelines 1. The symptoms of Type 1 von Willebrand disease include easy bruising, prolonged bleeding from cuts, nosebleeds, heavy menstrual periods in women, and excessive bleeding after surgery or dental procedures.

Key Characteristics of Type 1 VWD

• Inherited in an autosomal dominant pattern, meaning a person needs only one copy of the altered gene to develop the condition
• Characterized by mild to moderate bleeding symptoms
• Patients have reduced levels of VWF, typically 20-50% of normal
• Diagnosis requires correlation of clinical assessment and laboratory testing, including VWF antigen and ristocetin cofactor activity levels, as outlined in the 2008 NHLBI/NIH guidelines 1

Laboratory Values for Type 1 VWD

• VWF:Rco (IU/dL): >0.5–0.7
• VWF:Ag (IU/dL): <30
• FVIII: <30
• VWF:RCo/VWF:Ag Ratio: variable, but typically <0.5–0.7, as noted in the American Journal of Hematology 1

Treatment and Management

• Treatment typically involves desmopressin (DDAVP), which can be administered as a nasal spray or injection to temporarily increase VWF levels during bleeding episodes or before procedures
• For more severe cases or when DDAVP is ineffective, VWF concentrate replacement therapy may be necessary
• Antifibrinolytic medications like tranexamic acid can also help control bleeding by preventing blood clot breakdown, as recommended in the clinical and laboratory diagnosis of von Willebrand disease guidelines 1
• Patients should avoid aspirin and other medications that affect platelet function, and should inform all healthcare providers about their condition before undergoing procedures.

From the Research

Definition of Type 1 von Willebrand's Disease

• Type 1 von Willebrand's disease is a common autosomal inherited bleeding disorder caused by a partial quantitative deficiency of von Willebrand factor (VWF) 2, 3, 4, 5.
• It is characterized by a reduction in the levels of VWF, which is a multi-adhesive protein that binds platelets to exposed subendothelium and carries factor VIII in circulation 2.
• The reduction in VWF levels can lead to a variable bleeding tendency, with clinical manifestations mainly represented by mucous membrane and soft tissue bleeding 2, 4.

Diagnosis of Type 1 von Willebrand's Disease

• The diagnosis of Type 1 von Willebrand's disease can be challenging due to the great overlap of clinical phenotypes and laboratory parameters between healthy individuals and those with the disease 6.
• The established diagnostic criteria include a personal history of mucocutaneous bleeding, a family history, and low VWF levels, but these criteria do not always coexist 6.
• Laboratory tests, such as activated partial thromboplastin time, bleeding time, factor VIII: C Ristocetin cofactor, and VWF antigen, can be used to diagnose the disease, but there is no consensus laboratory cut-off for the diagnosis 5, 6.

Treatment of Type 1 von Willebrand's Disease

• The treatment of choice for Type 1 von Willebrand's disease is desmopressin, which induces secretion of autologous factor VIII and VWF into plasma 2, 3, 4.
• Desmopressin is effective in patients with factor VIII and VWF levels of 10 U/dL or over who have proved responsive to a test-infusion with the compound 2.
• In patients with severe Type 1 von Willebrand's disease or those who do not respond to desmopressin, factor VIII concentrates that are rich in VWF may be used as an alternative treatment 5.