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von Willebrand disorder(VWD)

MedGen UID:
22686
Concept ID:
C0042974
Disease or Syndrome
Synonyms: Hereditary von Willebrand disease; von Willebrand Diseases; von Willebrand's disease; VWD
SNOMED CT: von Willebrand disorder (128105004); Angiohemophilia (128105004); Pseudohemophilia type B (128105004); Vascular hemophilia (128105004); Constitutional thrombopathy (128105004); Factor VIII deficiency with vascular defect (128105004); von Willebrand disease (128105004); vWD - von Willebrand's disease (128105004); von Willebrand's disease (128105004); von Willebrand-Jurgens disease (128105004)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): VWF (12p13.31)
Related gene: GP1BA
 
Monarch Initiative: MONDO:0019565
Orphanet: ORPHA903

Disease characteristics

Excerpted from the GeneReview: von Willebrand Disease
Von Willebrand disease (VWD), a congenital bleeding disorder caused by deficient or defective plasma von Willebrand factor (VWF), may only become apparent on hemostatic challenge, and bleeding history may become more apparent with increasing age. Recent guidelines on VWD have recommended taking a VWF level of 30 or 40 IU/dL as a cutoff for those diagnosed with the disorder. Individuals with VWF levels greater than 30 IU/dL and lower than 50 IU/dL can be described as having a risk factor for bleeding. This change in guidelines significantly alters the proportion of individuals with each disease type. Type 1 VWD (~30% of VWD) typically manifests as mild mucocutaneous bleeding. Type 2 VWD accounts for approximately 60% of VWD. Type 2 subtypes include: Type 2A, which usually manifests as mild-to-moderate mucocutaneous bleeding; Type 2B, which typically manifests as mild-to-moderate mucocutaneous bleeding that can include thrombocytopenia that worsens in certain circumstances; Type 2M, which typically manifests as mild-moderate mucocutaneous bleeding; Type 2N, which can manifest as excessive bleeding with surgery and mimics mild hemophilia A. Type 3 VWD (<10% of VWD) manifests with severe mucocutaneous and musculoskeletal bleeding. [from GeneReviews]
Authors:
Anne Goodeve  |  Paula James   view full author information

Additional description

From MedlinePlus Genetics
Von Willebrand disease is a bleeding disorder that slows the blood clotting process, causing prolonged bleeding after an injury. People with this condition often experience easy bruising, long-lasting nosebleeds, and excessive bleeding or oozing following an injury, surgery, or dental work. Mild forms of von Willebrand disease may become apparent only when abnormal bleeding occurs following surgery or a serious injury. People with this condition who have menstrual periods typically have heavy or prolonged bleeding during menstruation (menorrhagia), and some may also experience reproductive tract bleeding during pregnancy and childbirth. In severe cases of von Willebrand disease, heavy bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Symptoms of von Willebrand disease may change over time. Increased age, pregnancy, exercise, and stress may cause bleeding symptoms to become less frequent.

Von Willebrand disease is divided into three types. Type 1 has one subtype (1C), and type 2 is divided into four subtypes (2A, 2B, 2M, and 2N). Type 1 is the most common of the three types, accounting for 75 percent of affected individuals. Type 1 is typically mild, but some people are severely affected. Type 2 accounts for about 15 percent of cases. This type is usually of intermediate severity. Type 3 is the rarest form of the condition, accounting for about 5 percent of affected individuals, and is usually the most severe. 

Another form of the disorder, acquired von Willebrand syndrome, is not caused by inherited gene variants (also called mutations).  Acquired von Willebrand syndrome is typically seen in people with other disorders, such as diseases that affect bone marrow or immune cell function. This rare form of the condition is characterized by abnormal bleeding into the skin and other soft tissues, usually beginning in adulthood.  https://medlineplus.gov/genetics/condition/von-willebrand-disease

Professional guidelines

PubMed

Shortt J, Opat SS, Gorniak MB, Aumann HA, Collecutt MF, Street AM
Int J Lab Hematol 2010 Feb;32(1 Pt 1):e181-3. Epub 2008 Oct 29 doi: 10.1111/j.1751-553X.2008.01117.x. PMID: 19016919
Naranja RJ Jr, Chan PS, High K, Esterhai JL Jr, Heppenstall RB
Orthopedics 1997 Aug;20(8):706-9; quiz 710-1. doi: 10.3928/0147-7447-19970801-10. PMID: 9263290

Recent clinical studies

Etiology

Icheva V, Nowak-Machen M, Budde U, Jaschonek K, Neunhoeffer F, Kumpf M, Hofbeck M, Schlensak C, Wiegand G
J Thromb Haemost 2018 Nov;16(11):2150-2158. Epub 2018 Sep 16 doi: 10.1111/jth.14208. PMID: 29908036
Favaloro EJ
Semin Thromb Hemost 2006 Jul;32(5):456-71. doi: 10.1055/s-2006-947859. PMID: 16862518
Favaloro EJ, Soltani S, McDonald J
Am J Clin Pathol 2004 Nov;122(5):686-92. doi: 10.1309/E494-7DG4-8TVY-19C2. PMID: 15491964
Favaloro EJ
Best Pract Res Clin Haematol 2001 Jun;14(2):299-319. doi: 10.1053/beha.2001.0135. PMID: 11686101
Susman-Shaw A
Nurs Stand 1999 Apr 14-20;13(30):39-44. doi: 10.7748/ns1999.04.13.30.39.c7466. PMID: 10418493

Diagnosis

Favaloro EJ
Semin Thromb Hemost 2006 Sep;32(6):566-76. doi: 10.1055/s-2006-949662. PMID: 16977567
Favaloro EJ
Semin Thromb Hemost 2006 Jul;32(5):456-71. doi: 10.1055/s-2006-947859. PMID: 16862518
Favaloro EJ
Curr Opin Hematol 2002 Sep;9(5):407-15. doi: 10.1097/00062752-200209000-00004. PMID: 12172459
Favaloro EJ
Best Pract Res Clin Haematol 2001 Jun;14(2):299-319. doi: 10.1053/beha.2001.0135. PMID: 11686101
Susman-Shaw A
Nurs Stand 1999 Apr 14-20;13(30):39-44. doi: 10.7748/ns1999.04.13.30.39.c7466. PMID: 10418493

Therapy

Howman R, Barnes C, Curtin J, Price J, Robertson J, Russell S, Seldon M, Suppiah R, Teague L, Barrese G
Haemophilia 2011 May;17(3):463-9. Epub 2010 Dec 1 doi: 10.1111/j.1365-2516.2010.02445.x. PMID: 21118340
Favaloro EJ, Lloyd J, Rowell J, Baker R, Rickard K, Kershaw G, Street A, Scarff K, Barrese G, Maher D, McLachlan AJ
Thromb Haemost 2007 Jun;97(6):922-30. PMID: 17549293
Shortt J, Dunkley S, Rickard K, Baker R, Street A
Haemophilia 2007 Mar;13(2):144-8. doi: 10.1111/j.1365-2516.2006.01430.x. PMID: 17286766
Favaloro EJ
Semin Thromb Hemost 2006 Jul;32(5):456-71. doi: 10.1055/s-2006-947859. PMID: 16862518
Favaloro EJ, Kershaw G, Bukuya M, Hertzberg M, Koutts J
Haemophilia 2001 Mar;7(2):180-9. doi: 10.1046/j.1365-2516.2001.00487.x. PMID: 11260278

Prognosis

Icheva V, Nowak-Machen M, Budde U, Jaschonek K, Neunhoeffer F, Kumpf M, Hofbeck M, Schlensak C, Wiegand G
J Thromb Haemost 2018 Nov;16(11):2150-2158. Epub 2018 Sep 16 doi: 10.1111/jth.14208. PMID: 29908036
Favaloro EJ
Semin Thromb Hemost 2006 Jul;32(5):537-45. doi: 10.1055/s-2006-947869. PMID: 16862528
Favaloro EJ
Curr Opin Hematol 2002 Sep;9(5):407-15. doi: 10.1097/00062752-200209000-00004. PMID: 12172459
Favaloro EJ, Kershaw G, Bukuya M, Hertzberg M, Koutts J
Haemophilia 2001 Mar;7(2):180-9. doi: 10.1046/j.1365-2516.2001.00487.x. PMID: 11260278

Clinical prediction guides

Icheva V, Nowak-Machen M, Budde U, Jaschonek K, Neunhoeffer F, Kumpf M, Hofbeck M, Schlensak C, Wiegand G
J Thromb Haemost 2018 Nov;16(11):2150-2158. Epub 2018 Sep 16 doi: 10.1111/jth.14208. PMID: 29908036
Shortt J, Dunkley S, Rickard K, Baker R, Street A
Haemophilia 2007 Mar;13(2):144-8. doi: 10.1111/j.1365-2516.2006.01430.x. PMID: 17286766
Favaloro EJ
Semin Thromb Hemost 2006 Jul;32(5):537-45. doi: 10.1055/s-2006-947869. PMID: 16862528
Favaloro EJ
Curr Opin Hematol 2002 Sep;9(5):407-15. doi: 10.1097/00062752-200209000-00004. PMID: 12172459
Favaloro EJ, Kershaw G, Bukuya M, Hertzberg M, Koutts J
Haemophilia 2001 Mar;7(2):180-9. doi: 10.1046/j.1365-2516.2001.00487.x. PMID: 11260278

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