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von Willebrand disease type 2(VWD2)

MedGen UID:
224736
Concept ID:
C1264040
Congenital Abnormality; Disease or Syndrome
Synonyms: VON WILLEBRAND DISEASE, TYPE 2A/IIE; VON WILLEBRAND DISEASE, TYPE 2CB; VON WILLEBRAND DISEASE, TYPE II; VWD, TYPE 2; VWD2
SNOMED CT: von Willebrand disease type 2 (128107007); Hereditary von Willebrand disease type 2 (128107007)
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)
 
Monarch Initiative: MONDO:0013304
OMIM®: 613554
Orphanet: ORPHA166081

Disease characteristics

Excerpted from the GeneReview: Von Willebrand Disease
Von Willebrand disease (VWD) is characterized by mucocutaneous bleeding and excessive bleeding with trauma and procedures. Individuals with more severe forms of VWD are also at-risk for musculoskeletal bleeding. Mucocutaneous bleeding can include easy bruising, prolonged bleeding from minor wounds, epistaxis, oral cavity bleeding, heavy menstrual bleeding, gastrointestinal bleeding, and bleeding with hemostatic challenges such as dental work, childbirth, and surgery. Bleeding severity can vary widely in VWD, even between affected individuals within the same family. For some with VWD the bleeding phenotype may only become apparent upon hemostatic challenge, while others may have frequent spontaneous bleeding. [from GeneReviews]
Authors:
Jill Johnsen   view full author information

Additional description

From OMIM
Von Willebrand disease is the most common inherited bleeding disorder. It is characterized clinically by mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma. It results from a defect in platelet aggregation due to defects in the von Willebrand factor. Von Willebrand factor is a large, multimeric protein that plays a role in platelet adhesion and also serves as a carrier for the thrombotic protein factor VIII (F8; 300841). F8 is mutated in hemophilia A (306700) (review by Goodeve, 2010). Whereas von Willebrand disease types 1 (193400) and 3 (277480) are characterized by quantitative defects in the VWF gene, von Willebrand disease type 2, which is divided in subtypes 2A, 2B, 2M, and 2N, is characterized by qualitative abnormalities of the VWF protein. The mutant VWF protein in types 2A, 2B, and 2M are defective in their platelet-dependent function, whereas the mutant protein in type 2N is defective in its ability to bind F8. VWD2 accounts for 20 to 30% of cases of VWD (Mannucci, 2004; Sadler et al., 2006; Lillicrap, 2009; Goodeve, 2010). For a general discussion and a classification of the types of von Willebrand disease, see VWD type 1 (193400).  http://www.omim.org/entry/613554

Clinical features

From HPO
Epistaxis
MedGen UID:
4996
Concept ID:
C0014591
Pathologic Function
Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose.
Menorrhagia
MedGen UID:
44358
Concept ID:
C0025323
Pathologic Function
Prolonged and excessive menses at regular intervals in excess of 80 mL or lasting longer than 7 days.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.

Professional guidelines

PubMed

Maas DPMSM, Atiq F, Blijlevens NMA, Brons PPT, Krouwel S, Laros-van Gorkom BAP, Leebeek FWG, Nieuwenhuizen L, Schoormans SCM, Simons A, Meijer D, van Heerde WL, Schols SEM
J Thromb Haemost 2022 Feb;20(2):316-327. Epub 2021 Nov 21 doi: 10.1111/jth.15586. PMID: 34758185Free PMC Article
Mannucci PM, Federici AB
Best Pract Res Clin Haematol 2001 Jun;14(2):455-62. doi: 10.1053/beha.2001.0143. PMID: 11686109
Lusher JM
Am J Obstet Gynecol 1996 Sep;175(3 Pt 2):778-83. doi: 10.1016/s0002-9378(96)80084-6. PMID: 8828561

Recent clinical studies

Etiology

Ryu JH, Bauer KA, Schulman S
J Thromb Haemost 2023 Dec;21(12):3508-3510. Epub 2023 Sep 20 doi: 10.1016/j.jtha.2023.09.009. PMID: 37734716
Noone S, Schubert R, Fichtlscherer S, Hilberg T, Alesci S, Miesbach W
Clin Appl Thromb Hemost 2021 Jan-Dec;27:1076029620984546. doi: 10.1177/1076029620984546. PMID: 33448867Free PMC Article
Goodeve A
Hematology Am Soc Hematol Educ Program 2016 Dec 2;2016(1):678-682. doi: 10.1182/asheducation-2016.1.678. PMID: 27913546Free PMC Article
Mikhail S, Aldin ES, Streiff M, Zeidan A
Expert Rev Hematol 2014 Apr;7(2):217-31. Epub 2014 Feb 12 doi: 10.1586/17474086.2014.868771. PMID: 24521271
Goodeve AC
Blood Rev 2010 May;24(3):123-34. Epub 2010 Apr 20 doi: 10.1016/j.blre.2010.03.003. PMID: 20409624

Diagnosis

Seidizadeh O, Peyvandi F, Mannucci PM
J Thromb Haemost 2021 Apr;19(4):909-916. Epub 2021 Mar 26 doi: 10.1111/jth.15247. PMID: 33497541
Leebeek FWG, Atiq F
Br J Haematol 2019 Nov;187(4):418-430. Epub 2019 Sep 9 doi: 10.1111/bjh.16186. PMID: 31498884Free PMC Article
Sharma R, Flood VH
Hematology Am Soc Hematol Educ Program 2017 Dec 8;2017(1):379-384. doi: 10.1182/asheducation-2017.1.379. PMID: 29222282Free PMC Article
Goodeve A
Hematology Am Soc Hematol Educ Program 2016 Dec 2;2016(1):678-682. doi: 10.1182/asheducation-2016.1.678. PMID: 27913546Free PMC Article
Mikhail S, Aldin ES, Streiff M, Zeidan A
Expert Rev Hematol 2014 Apr;7(2):217-31. Epub 2014 Feb 12 doi: 10.1586/17474086.2014.868771. PMID: 24521271

Therapy

Kruse-Jarres R, Johnsen JM
Blood 2018 Mar 22;131(12):1292-1300. Epub 2018 Jan 29 doi: 10.1182/blood-2017-06-742692. PMID: 29378695
Sharma R, Flood VH
Hematology Am Soc Hematol Educ Program 2017 Dec 8;2017(1):379-384. doi: 10.1182/asheducation-2017.1.379. PMID: 29222282Free PMC Article
Favaloro EJ, Pasalic L, Curnow J
Semin Thromb Hemost 2016 Jul;42(5):483-97. Epub 2016 May 5 doi: 10.1055/s-0036-1579641. PMID: 27148841
Mikhail S, Aldin ES, Streiff M, Zeidan A
Expert Rev Hematol 2014 Apr;7(2):217-31. Epub 2014 Feb 12 doi: 10.1586/17474086.2014.868771. PMID: 24521271
Lillicrap D
Hematology Am Soc Hematol Educ Program 2013;2013:254-60. doi: 10.1182/asheducation-2013.1.254. PMID: 24319188

Prognosis

Daniel MY, Ternisien C, Castet S, Falaise C, D'Oiron R, Volot F, Itzhar N, Pan-Petesch B, Jeanpierre E, Paris C, Zawadzki C, Desvages M, Dupont A, Veyradier A, Repessé Y, Babuty A, Trossaërt M, Boisseau P, Denis CV, Lenting PJ, Goudemand J, Rauch A, Susen S
J Thromb Haemost 2024 Oct;22(10):2702-2712. Epub 2024 Jul 9 doi: 10.1016/j.jtha.2024.06.020. PMID: 38992343
Seidizadeh O, Mollica L, Zambarbieri S, Baronciani L, Cairo A, Colpani P, Cozzi G, Pagliari MT, Ciavarella A, Siboni SM, Peyvandi F
Blood Adv 2024 Apr 9;8(7):1725-1736. doi: 10.1182/bloodadvances.2024012626. PMID: 38315875Free PMC Article
Kranzhöfer D, Pavlova A, Schneider H, Franck P, Glonnegger H, Büchsel M, Yoshimi-Nöllke A, Oldenburg J, Zieger B
Hamostaseologie 2021 Dec;41(6):469-474. Epub 2021 Dec 23 doi: 10.1055/a-1665-6185. PMID: 34942660
Favaloro EJ, Bonar RA, Mohammed S, Arbelaez A, Niemann J, Freney R, Meiring M, Sioufi J, Marsden K
Haemophilia 2016 May;22(3):e145-55. Epub 2016 Mar 31 doi: 10.1111/hae.12903. PMID: 27029718
Tosetto A, Castaman G
Blood 2015 Feb 5;125(6):907-14. Epub 2014 Dec 4 doi: 10.1182/blood-2014-08-551960. PMID: 25477497

Clinical prediction guides

Daniel MY, Ternisien C, Castet S, Falaise C, D'Oiron R, Volot F, Itzhar N, Pan-Petesch B, Jeanpierre E, Paris C, Zawadzki C, Desvages M, Dupont A, Veyradier A, Repessé Y, Babuty A, Trossaërt M, Boisseau P, Denis CV, Lenting PJ, Goudemand J, Rauch A, Susen S
J Thromb Haemost 2024 Oct;22(10):2702-2712. Epub 2024 Jul 9 doi: 10.1016/j.jtha.2024.06.020. PMID: 38992343
Maas DPMSM, Atiq F, Blijlevens NMA, Brons PPT, Krouwel S, Laros-van Gorkom BAP, Leebeek FWG, Nieuwenhuizen L, Schoormans SCM, Simons A, Meijer D, van Heerde WL, Schols SEM
J Thromb Haemost 2022 Feb;20(2):316-327. Epub 2021 Nov 21 doi: 10.1111/jth.15586. PMID: 34758185Free PMC Article
Freitas SDS, Rezende SM, de Oliveira LC, Prezotti ANL, Renni MS, Corsini CA, Amorim MVA, Matosinho CGR, Carvalho MRS, Chaves DG
Haemophilia 2019 Mar;25(2):e78-e85. Epub 2019 Feb 28 doi: 10.1111/hae.13714. PMID: 30817071
Adam F, Casari C, Prévost N, Kauskot A, Loubière C, Legendre P, Repérant C, Baruch D, Rosa JP, Bryckaert M, de Groot PG, Christophe OD, Lenting PJ, Denis CV
Sci Rep 2016 May 23;6:26306. doi: 10.1038/srep26306. PMID: 27212476Free PMC Article
Castaman G, Federici AB
Semin Thromb Hemost 2016 Jul;42(5):478-82. Epub 2016 May 5 doi: 10.1055/s-0036-1579638. PMID: 27148840

Recent systematic reviews

Kalot MA, Husainat N, Abughanimeh O, Diab O, El Alayli A, Tayiem S, Madoukh B, Dimassi A, Qureini A, Ameer B, Eikenboom J, Giraud N, Haberichter S, Jacobs-Pratt V, Konkle BA, McRae S, Montgomery R, O'Donnell JS, Brignardello-Petersen R, Flood V, Connell NT, James P, Mustafa RA
Blood Adv 2022 Jun 28;6(12):3735-3745. doi: 10.1182/bloodadvances.2021005431. PMID: 35192687Free PMC Article
Makhamreh MM, Russo ML, Karl T, Delgado N, Lackritz K, Skupski DW, Al-Kouatly HB
Semin Thromb Hemost 2021 Mar;47(2):201-216. Epub 2021 Feb 26 doi: 10.1055/s-0041-1723799. PMID: 33636751

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