History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include positive family history and consanguineous relationships.

family history of VWD and bleeding

A strong indicator for von Willebrand disease (VWD). May be absent in some types of VWD.

Patients with type 1 VWD may or may not have a family history of VWD or bleeding symptoms. Type 1 VWD generally exhibits an autosomal dominant inheritance pattern. However, a family history may be absent because type 1 VWD may not be linked to inherited mutations in the VWF gene, particularly in patients with milder disease. Furthermore, inheritance of type 1 VWD is complicated by incomplete penetrance and variable expressivity.[40][41]

Patients with type 2A, 2B, and 2M VWD generally have a family history of VWD or bleeding symptoms that is clearly autosomal dominant. Most mutations associated with type 2 VWD are fully penetrant.[40][41]

Patients with type 2N or type 3 VWD may or may not have a family history of VWD or bleeding symptoms due to its autosomal recessive inheritance pattern. Family members who are heterozygotes (i.e., carriers) for type 2N or type 3 VWD (i.e., carriers) are usually asymptomatic and may be undiagnosed.

easy and excessive bruising

Easy and excessive bruising (e.g., very large bruises, or bruising on the trunk or other areas not normally exposed to injury) is common in von Willebrand disease (VWD).[8][9]​​

Bleeding symptoms are usually more severe in type 2 and 3 VWD than type 1 VWD, and may begin at an earlier age.[8][9]​​

Bleeding in infancy is rare, although young children may bruise more easily.

bleeding from trauma or minor wounds

Excessive or prolonged bleeding from trauma or minor wounds is common in von Willebrand disease (VWD).[8][9]​​

Bleeding symptoms are usually more severe in people with type 2 and 3 VWD than type 1 VWD, and may begin at an earlier age.[8][9]

mucosal bleeding (e.g., epistaxis, gum bleeding)

Excessive mucosal bleeding (e.g., epistaxis, gum bleeding) is common in von Willebrand disease (VWD).[8][9]​​​

Bleeding may be prolonged (>30 minutes) and medical intervention may be required to control bleeding.

Bleeding symptoms are usually more severe in people with type 2 and 3 VWD than type 1 VWD, and may begin at an earlier age.[8][9]

Younger patients may have problems with epistaxis, which is especially common in boys.[42]

Patients with chronic epistaxis may have a history compatible with anaemia due to ongoing blood loss and iron deficiency.

heavy menstrual bleeding (HMB)

HMB is common in women and girls with von Willebrand disease (VWD).[8][9]​​

Girls with VWD may have HMB from the onset of menarche.

Menses associated with soaking pads within 1 hour, anaemia, decreased ferritin, and a pictorial blood assessment chart score >100 strongly correlate with a diagnosis of HMB.[53][54]

Patients with HMB may give histories compatible with anaemia due to ongoing blood loss and iron deficiency.

postpartum haemorrhage

Postpartum haemorrhage is common in women with von Willebrand disease.[8][9]​​

post-operative bleeding

Excessive bleeding after invasive surgical procedures is common in von Willebrand disease (VWD), particularly in those with severe disease (e.g., type 3 VWD) and if procedures involve the mucous membrane (e.g., tonsillectomy, dental extraction).[9][8] Some patients may need to return to hospital to control rebleeding.

Bleeding symptoms are usually more severe in people with type 2 and 3 VWD than type 1 VWD, and may begin at an earlier age.[9][8]

Other diagnostic factors

common

gastrointestinal bleeding

More common in patients with type 2 or 3 VWD than type 1 VWD.[8][9]​​[12]

Patients should be evaluated for an anatomical cause. Gastrointestinal bleeding is also associated with angiodysplasia, particularly in the context of aortic stenosis and acquired von Willebrand syndrome.

Patients with gastrointestinal bleeding may have a history compatible with anaemia due to ongoing blood loss and iron deficiency.

Recurrent gastrointestinal bleeding may be a significant medical problem, particularly in older patients.

uncommon

history of repeat blood transfusions

Patients with von Willebrand disease may have a history of requiring repeat blood transfusion for post-operative bleeding or significant anaemia.

joint bleeding (haemarthrosis)

Evidence of joint bleeding (e.g., swelling) is rare and usually only occurs in patients with severe disease and markedly decreased FVIII levels (e.g., type 3 VWD).[8][9]​​[12]

haematuria

Uncommon in von Willebrand disease (VWD).[7][9]

VWD may exacerbate risk of bleeding from underlying genitourinary tract lesions.[55] Patients should be evaluated for an anatomical cause.

Bleeding symptoms are usually more severe in people with type 2 and type 3 VWD than type 1 VWD, and may begin at an earlier age.[8][9]​​

Patients with persistent haematuria may give histories compatible with anaemia due to ongoing blood loss and iron deficiency.

central nervous system bleeding

Uncommon in von Willebrand disease (VWD).[8][10][11]

Occurs more commonly with severe disease (e.g., type 3 VWD).[8][10][11][12]

Risk factors

strong

positive family history

Von Willebrand disease (VWD) is usually due to an inherited mutation in the VWF gene.[1][20]

Patients with type 1 VWD may have a family history of VWD or bleeding symptoms that exhibit an autosomal dominant inheritance pattern. However, a family history is not always present because some cases of type 1 VWD are not linked to inherited mutations in the VWF gene, particularly cases with milder disease. Furthermore, inheritance of type 1 VWD is often complicated by incomplete penetrance and variable expressivity.[40][41]

Patients with type 2A, 2B, and 2M VWD generally have a family history of VWD or bleeding symptoms that clearly exhibits an autosomal dominant pattern. Most mutations associated with type 2 VWD are fully penetrant.[40][41]

Patients with type 2N or type 3 VWD may or may not have a family history of VWD or bleeding symptoms due to its autosomal recessive inheritance pattern. Family members who are heterozygotes for type 2N or type 3 VWD (i.e., carriers) are usually asymptomatic and may be undiagnosed.

consanguineous relationships

Type 3 von Willebrand disease (the most severe type) is more common in countries or regions where consanguineous relationships are accepted.[16]

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