Penetrance

Type 1 VWD (autosomal dominant). VWD-causing variants resulting in plasma VWF levels lower than 30 IU/dL tend to be more penetrant. Other autosomal dominant types (2A, 2B, and 2M). VWD-causing variants are often fully penetrant, particularly for type 2A and type 2B VWD.

Source: GeneReviews — "Von Willebrand Disease"

Diagnostic Criteria

International guidelines on the diagnosis of von Willebrand disease (VWD) have been published .

Suggestive Findings

VWD should be suspected in probands with the following clinical and laboratory findings.

Clinical findings

Source: GeneReviews — "Von Willebrand Disease"

Differential Diagnosis

Mild-to-moderate hemophilia A and platelet-type von Willebrand disease (PT-VWD) can be difficult to distinguish phenotypically from von Willebrand disease (VWD) .

Table 4.

Genetic Disorders in the Differential Diagnosis of von Willebrand Disease

Gene | Disorder | MOI | Phenotype | Diagnosis

Source: GeneReviews — "Von Willebrand Disease"

Management Guidelines

Clinical practice guidelines for von Willebrand disease (VWD) have been published .

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with VWD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 5.

Von Willebrand Disease: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Hematology

| • Ensure complete modern VWD eval has been performed whenever possible prior to invasive procedures or other hemostatic risks.

• Assess history of bleeding.

• Assess VWF levels.

• Assess FVIII levels.

| Very old or historical diagnoses of VWD w/o recent laboratory confirmation should not be relied upon in treatment planning.

VWF inhibitor testing (when available) in those w/type 3 VWD or suspected presence of inhibitors |

CBC; iron studies incl ferritin | To assess for anemia iron deficiency to identify persons who should have iron replacement

Musculoskeletal

| Joint muscle eval (as would be done for persons w/hemophilia A) | In those w/low FVIII levels or clinical suspicion

Gynecology

| Gynecologic eval for those w/heavy menstrual bleeding /or ovarian hemorrhage (See also .) | To assess for other anatomic contributors to bleeding to coordinate mgmt w/hormonal therapies, IUD, procedures if needed

Gastrointestinal

| Endoscopic eval for anatomic causes of bleeding, incl angiodysplasia in those w/suspected GI bleeding |

Infectious disease

| Screening for ...

Source: GeneReviews — "Von Willebrand Disease"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 8.

Von Willebrand Disease: Recommended Surveillance

System/Concern | Evaluation | Frequency

Hematology

| • Assessment at hematology treatment center w/experience w/bleeding disorders

• Determination of frequency of bleeding, factors causing incr bleeding, treatment efficacy tolerability

• CBC iron levels

• VWF levels

• Assess for VWD inhibitors in those at risk (type 3 VWD)

| • Annually, particularly in those receiving treatment

• Every 2-3 years in those w/o bleeding not on treatment

Musculoskeletal

| • Assessment of joint scores mobility by PT

• Musculoskeletal ultrasound when applicable

| In those w/more severe VWD /or low FVIII levels, or w/evidence of musculoskeletal bleeding, assess on same schedule as hemophilia A.

Gynecology

| Gynecologic eval | As needed for females w/heavy menstrual bleeding or other reproductive tract bleeding

Gastrointestinal

| Gastroenterology eval for iron deficiency, anemia, or signs of GI bleeding | At time of active bleeding per gastroenterologist recommendation

Infectious disease

| Assessment by specialist in hepatitis B /or hepatitis C (usually hepatologist) HIV infection (usually infectious disease specialist); surveillance is disease specific may incl monitoring viral load, antiviral titer, liver imaging or biopsy, liver function tests, hepatocellular carcinoma surveillance, blood counts, eval o...

Source: GeneReviews — "Von Willebrand Disease"