Von Willebrand disease

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 18 Nov 2025

Last updated: 11 Dec 2025

Von Willebrand disease (VWD) is the most common inherited bleeding disorder. Type 1 VWD is more common and less severe than type 2 and 3 VWD.

VWD usually presents with mucocutaneous bleeding or bleeding after trauma or surgery. Heavy menstrual bleeding and postpartum hemorrhage are common in women with VWD. Joint bleeding is rare and usually only occurs in patients with severe disease (e.g., type 3 VWD).

Bleeding assessment tools (BATs) can help identify patients with VWD and guide referral for diagnostic testing.

Diagnosis requires blood tests to assess von Willebrand factor (VWF) antigen (VWF:Ag), platelet-dependent VWF activity (e.g., using VWF:GPIbM assay), and factor VIII coagulant activity (FVIII:C).

Management involves preventing and treating bleeding symptoms based on the specific type of VWD. Treatment options include desmopressin, VWF-containing concentrate, and antifibrinolytic therapy.

Definition

VWD is a bleeding disorder characterized by quantitative deficiency or qualitative defects of the VWF protein due to inherited mutations in the VWF gene.[1] VWF is critical for blood clotting as it facilitates platelet adhesion to exposed vascular subendothelium, and also binds and stabilizes coagulation factor VIII (FVIII).[1]

VWD is categorized into three main types (1, 2, and 3) based on whether the cause is a deficiency or defect of VWF.

Rarely, patients may develop acquired von Willebrand syndrome (AVWS) secondary to a lymphoproliferative, myeloproliferative, autoimmune, cardiovascular, or other disorder.[2][3][4] Details on the diagnosis and management of AVWS are beyond the scope of this topic.

History and exam

Key diagnostic factors

family history of VWD and bleeding
easy and excessive bruising
bleeding from trauma or minor wounds
mucosal bleeding (e.g., epistaxis, gum bleeding)
heavy menstrual bleeding (HMB)
postpartum hemorrhage
postoperative bleeding

Full details

Other diagnostic factors

gastrointestinal bleeding
history of repeat blood transfusions
joint bleeding (hemarthrosis)
hematuria
central nervous system bleeding

Full details

Risk factors

positive family history
consanguineous relationships

Full details

Diagnostic tests

1st tests to order

CBC
prothrombin time (PT)
activated partial thromboplastin time (aPTT)
von Willebrand factor (VWF) antigen (VWF:Ag)
von Willebrand factor (VWF) platelet-binding activity assay (VWF:GPIbM, VWF:GPIbR, or VWF:RCo)
factor VIII (FVIII) coagulant activity assay (FVIII:C)

Full details

Tests to avoid

bleeding time test

Full details

Tests to consider

fibrinogen
thrombin time
von Willebrand factor (VWF) multimer analysis
von Willebrand factor (VWF) collagen binding assay (VWF:CB)
genetic testing (for type 2B or 2N VWD variants)
low-dose ristocetin-induced platelet agglutination (RIPA) mixing studies
von Willebrand factor (VWF) FVIII binding assay (VWF:FVIIIB)
VWF propeptide assay (VWFpp/VWF:Ag)
platelet function analyzer (e.g., PFA-100)

Full details

Treatment algorithm

INITIAL

VWD type unknown with bleeding

all types VWD with severe bleeding uncontrolled by other VWD-specific therapies

ACUTE

all types VWD with severe bleeding or before invasive procedures where sustained elevation of VWF levels is necessary: nonpregnant

minor bleeding or minor invasive procedures involving mucous membranes: nonpregnant

minor bleeding or minor invasive procedures not involving mucous membranes: nonpregnant

all types VWD: pregnant

ONGOING

all types VWD with heavy menstrual bleeding

all types VWD with significant chronic or recurrent bleeding

Contributors

Authors

Craig Seaman, MD, MS

Assistant Professor of Medicine

Division of Hematology/Oncology

Associate Director

Hemophilia Center of Western Pennsylvania

Pittsburgh

Disclosures

CS is a consultant for Takeda Pharmaceuticals.

Acknowledgements

Dr. Craig Seaman would like to gratefully acknowledge Professor Mike Laffan and Dr Barbara A. Konkle, previous contributors to this topic.

Disclosures

ML declares he has received consultancy fees from Pfizer, Takeda, Sobi, CSL Behring, AstraZeneca, and Roche; and speaker fees from: Pfizer, Takeda, CSL Behring, Sobi, AstraZeneca, Leo Pharma, and Bayer; and travel support from Bayer and Shire. ML is an author of several references cited in this topic. BAK declares that she has no competing interests.

Peer reviewers

Margaret Ragni, MD

Director

Hemophilia Center of Western Pennsylvania

Pittsburgh

Disclosures

MR is an author of a reference cited in this topic.

David Keeling, BSc, MD, FRCP, FRCPath

Consultant Haematologist and Director

Oxford Haemophilia & Thrombosis Centre

Churchill Hospital

Oxford

Disclosures

DK declares that he has received payments from CSL Behring for giving a lecture and attending an advisory board. He is an author of a number of references cited in this topic.

Peer reviewer acknowledgements

BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.

Disclosures

Peer reviewer affiliations and disclosures pertain to the time of the review.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Sadler JE, Budde U, Eikenboom JC, et al. Update on the pathophysiology and classification of von Willebrand disease: a report of the subcommittee on von Willebrand factor. J Thromb Haemost. 2006 Oct;4(10):2103-14.Full text Abstract

Pavord S, Rayment R, Madan B, et al; on behalf of the Royal College of Obstetricians and Gynaecologists. Management of inherited bleeding disorders in pregnancy. Green-top guideline No 71 (joint with UKHCDO). BJOG. 2017 Jul;124(8):e193–263.Full text Abstract

James PD, Connell NT, Ameer B, et al. ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease. Blood Adv. 2021 Jan 12;5(1):280-300.Full text Abstract

Laffan MA, Lester W, O'Donnell JS, et al. The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology. Br J Haematol. 2014 Nov;167(4):453-65.Full text Abstract

Platton S, Baker P, Bowyer A, et al. Guideline for laboratory diagnosis and monitoring of von Willebrand disease: a joint guideline from the United Kingdom Haemophilia Centre Doctors' Organisation and the British Society for Haematology. Br J Haematol. 2024 May;204(5):1714-31.Full text Abstract

Connell NT, Flood VH, Brignardello-Petersen R, et al. ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease. Blood Adv. 2021 Jan 12;5(1):301-25.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Mild hemophilia A
- Inherited platelet function disorder
- Acquired von Willebrand syndrome
More Differentials
Guidelines
- Guideline for laboratory diagnosis and monitoring of von Willebrand disease: a joint guideline from the United Kingdom Haemophilia Centre Doctors' Organisation and the British Society for Haematology
- MASAC recommendations on administration of vaccines to individuals with bleeding disorders
More Guidelines
Patient information
Heavy periods
More Patient information
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Von Willebrand disease

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to avoid

Tests to consider

Treatment algorithm

VWD type unknown with bleeding

all types VWD with severe bleeding uncontrolled by other VWD-specific therapies

all types VWD with severe bleeding or before invasive procedures where sustained elevation of VWF levels is necessary: nonpregnant

minor bleeding or minor invasive procedures involving mucous membranes: nonpregnant

minor bleeding or minor invasive procedures not involving mucous membranes: nonpregnant

all types VWD: pregnant

all types VWD with heavy menstrual bleeding

all types VWD with significant chronic or recurrent bleeding

Contributors

Authors

Craig Seaman, MD, MS

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Margaret Ragni, MD

Disclosures

David Keeling, BSc, MD, FRCP, FRCPath

Disclosures

Peer reviewer acknowledgements

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Patient information

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice