Von Willebrand disease

Información en español Title

Not a rare disease

Other Names:

VWD; Von Willebrand factor, deficiency

Categories:

Blood Diseases

Summary Summary

Von Willebrand disease is a bleeding disorder that slows the blood clotting process. People with this disease often experience bruising, nosebleeds, and prolonged bleeding or oozing following an injury, affer surgery, or having a tooth pulled. Affected women may have heavy menstrual bleeding. In severe cases, heavy bleeding occurs after minor injury or even in the absence of injury. It is divided into three types. Type 1 is the mildest and most common, and type 3 is the most severe and rarest form. Type 2 (four subtypes) is intermediate in severity. Increased age, pregnancy, exercise, and stress may cause von Willebrand factor levels in the blood to rise, which can make bleeding symptoms less frequent. This disease is caused by mutations in the VWF gene and can have different inheritance patterns.^[1] Treatment varies according to the severity of the disease and includes plasma-derived clotting factor concentrates, and other medications.^[2]

Last updated: 8/17/2016

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Aortic valve stenosis	-
Autosomal dominant inheritance	-
Bruising susceptibility	-
Epistaxis	-
Gastrointestinal angiodysplasia	-
Gastrointestinal hemorrhage	-
Impaired platelet aggregation	-
Incomplete penetrance	-
Joint hemorrhage	-
Menorrhagia	-
Mitral valve prolapse	-
Prolonged bleeding time	-
Prolonged whole-blood clotting time	-
Reduced factor VIII activity	-

Last updated: 9/1/2016

Cause Cause

Von Willebrand disease is typically an inherited disease caused by mutations in the VWF gene. The VWF gene provides instructions for making a blood clotting protein called von Willebrand factor, which is important for forming blood clots and preventing further blood loss after an injury. If von Willebrand factor does not function normally or too little of the protein is available, blood clots cannot form properly. VWF gene mutations that reduce the amount of von Willebrand factor or cause the protein to function abnormally (or not at all) are responsible for the signs and symptoms associated with the condition. These mutations may be inherited in an autosomal dominant or autosomal recessive manner, or may occur for the first time in the affected individual (known as a de novo mutation).^[3]

Another form of the disorder, often considered a separate condition, is called acquired von Willebrand syndrome (AVWS). AVWS is not caused by gene mutations. This condition is typically seen in conjunction with other disorders and usually begins in adulthood.^[3] A list of disorders associated with AVWS is available from UpToDate.^[4]

Last updated: 8/17/2016

Inheritance Inheritance

Most, but not all, cases of von Willebrand disease (VWD) are inherited. The majority of cases of type 1 and type 2A, as well as type 2B and type 2M, are inherited in an autosomal dominant manner. VWD type 2N, type 3, and some cases of type 1 and type 2A are inherited in an autosomal recessive manner.^[5]

Most individuals with an autosomal dominant type of VWD have an affected parent. However, some individuals are affected due to having a new (de novo) mutation in the VWF gene that occurred for the first time in the affected individual. If the mutation found in the affected individual cannot be detected in either parent, it is most often due to a de novo mutation but may also be due to germline mosaicism in a parent. Possible non-medical explanations which may be explored include alternate paternity or maternity (e.g., with assisted reproduction) or undisclosed adoption.^[5]

There is also a separate, rare condition called acquired von Willebrand syndrome (AVWS). This is a mild to moderate bleeding disorder that is typically seen in conjunction with other disorders, such as diseases that affect bone marrow or immune cell function. AVWS is not caused by a mutation in the VWF gene and usually begins in adulthood.^[5]^[3]

Last updated: 8/17/2016

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
The National Hemophilia Foundation Web site posts the guidelines for management of pregnancy and delivery of women with bleeding disorders and carriers of hemophilia A and B. Click on the link to view the guidelines.
Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.
The National Heart, Blood and Lung Institute (NHLBI) assembled a panel of experts on von Willebrand to develop clinical management guidelines. To view the guidelines, click on the link.

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Antihemophilic factor (human) (Brand name: Alphanate®) - Manufactured by Grifols Biologicals Inc.
FDA-approved indication: For surgical and/or invasive procedures in patients with von Willebrand Disease (VWD) in whom desmopressin is either ineffective or contraindicated. It is not indicated for patients with severe VWD (Type 3) undergoing major surgery
National Library of Medicine Drug Information Portal
Medline Plus Health Information
Antihemophilic factor/von Willebrand factor complex (human), dried, pasteurized (Brand name: Humate-P®) - Manufactured by CSL Behring
FDA-approved indication: (1) In adult patients for treatment and prevention of bleeding in hemophilia A (classic hemophilia) and (2) in adult and pediatric patients for treatment of spontaneous and trauma-induced bleeding episodes in severe von Willebrand disease, and in mild and
National Library of Medicine Drug Information Portal
Medline Plus Health Information
Desmopressin acetate (Brand name: Stimate®) - Manufactured by CSL Behring
FDA-approved indication: Treatment of patients with hemophilia A or von Willebrand's disease (type I) whose factor VIII coagulant activity level is greater than 5%.
National Library of Medicine Drug Information Portal
Human Plasma Coagulation Factor VIII And Human Plasma Von Willebrand Factor (Brand name: Wilate(R)) - Manufactured by Octapharma USA, Inc.
FDA-approved indication: Treatment of spontaneous or trauma-induced bleeding episodes in patients with severe von Willebrand disease (VWD) as well as patients with mild or moderate VWD in whom the use of desmopressin is known or suspected to be ineffective or contraindicated
National Library of Medicine Drug Information Portal

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Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Von Willebrand disease. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Canadian Hemophilia Society
400-1255 University St
Montreal, QC H3B 3B6
Canada
Toll-free: 800-668-2686
Telephone: 514-848-0503
Fax: 514 848-9661
E-mail: chs@hemophilia.ca
Website: http://www.hemophilia.ca
National Hemophilia Foundation
7 Penn Plaza, Suite 1204
New York, NY 10001
Toll-free: 800-42-HANDI
Telephone: 212-328-3700
Fax: 212-328-3799
E-mail: handi@hemophilia.org
Website: http://www.hemophilia.org/
National Hemophilia Foundation
7 Penn Plaza, Suite 1204
New York, NY 10001
Toll-free: 800-42-HANDI
Telephone: 212-328-3700
Fax: 212-328-3799
E-mail: handi@hemophilia.org
Website: http://www.hemophilia.org/
World Federation of Hemophilia
1425 Rene Levesque Blvd. W.
Suite 1010
Montreal, Quebec H3G 1T7
Canada
Telephone: 514-875-7944
Fax: 514-875-8916
E-mail: wfh@wfh.org
Website: http://www.wfh.org/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Healthcare Resources

The Division of Blood Disorders at the Centers for Disease Control and Prevention has created specialized programs for persons with blood disorders and their families. One of the activities of the division involves the collaboration with networks of specialized health care centers throughout the United States. To locate treatment centers, organizations, and staff that are part of the federally funded network, click on the link.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

You can obtain information on this topic from the Centers for Disease Control and Prevention (CDC). The CDC is recognized as the lead federal agency for developing and applying disease prevention and control, environmental health, and health promotion and education activities designed to improve the health of the people of the United States.
Genetics Home Reference (GHR) contains information on Von Willebrand disease. This website is maintained by the National Library of Medicine.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers.
The National Heart, Lung, and Blood Institute (NHLBI) has information on this topic. NHLBI is part of the National Institutes of Health and supports research, training, and education for the prevention and treatment of heart, lung, and blood diseases.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
PubMed is a searchable database of medical literature and lists journal articles that discuss Von Willebrand disease. Click on the link to view a sample search on this topic.

News & Events News & Events

News

World Federation of Hemophilia
July 19, 2016

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I have two patients, a husband and wife, whose son has Von Willebrand disease. Neither of the parents had any positive blood tests for the disease. How did the child develop the disease, and if it was inherited from the parents why are they negative in all lab tests? Also, can pregnancy trigger such an issue? The mother had miscarriages prior to having their son. See answer

Have a question? Contact a GARD Information Specialist.

References References

Von Willebrand disease. Genetics Home Reference. 2012; http://ghr.nlm.nih.gov/condition/von-willebrand-disease.
Goodeve A & James P. von Willebrand Disease. GeneReviews. 2014; http://www.ncbi.nlm.nih.gov/books/NBK7014/#von-willebrand.Differential_Diagnosis.
Von Willebrand disease. Genetics Home Reference. 2012; http://ghr.nlm.nih.gov/condition/von-willebrand-disease.
Margaret E Rick. Classification and pathophysiology of von Willebrand disease. UpToDate. Waltham, MA: UpToDate, Inc; 2012;
Goodeve A & James P. von Willebrand Disease. GeneReviews. 2014; http://www.ncbi.nlm.nih.gov/books/NBK7014/.