Details of Disease

General Information of Disease (ID: DIS3TZCH)

• Disease Name: Von willebrand disease
• Synonyms: von Willebrand disease; von Willebrand's disease; VWD; Von Willebrand Disease; von Willebrand disorder
• Disease Class: 3B12: Von Willebrand disease
• Definition: Hereditary or acquired coagulation disorder characterized by a qualitative or quantitative deficiency of the von Willebrand factor. The latter plays an important role in platelet adhesion. Signs and symptoms include bruises, nose bleeding, gum bleeding following a dental procedure, heavy menstrual bleeding, and gastrointestinal bleeding.
• Disease Hierarchy:
  DISEXNCF: Coagulation protein disease
  DIS3TZCH: Von willebrand disease
• ICD Code:
  ICD-11: ICD-11: 3B12
  ICD-10: ICD-10: D68.0
  Expand ICD-11: '3B12
  Expand ICD-10: 'D68.0
• Disease Identifiers:
  MONDO ID: MONDO_0024574
  MESH ID: D014842
  UMLS CUI: C0042974
  MedGen ID: 22686
  SNOMED CT ID: 128105004

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 3 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Desmopressin	DMS3GVE	Approved	Small molecular drug	[1]
Vasopressin	DMQ2FPC	Approved	Small molecular drug	[2]
Vonvendi	DMI783H	Approved	Recombinant protein	[3]

This Disease is Treated as An Indication in 2 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Recombinant von Willebrand factor/recombinant Factor VIII complex	DM7JFDO	Phase 3	NA	[4]
BT-200	DM1EYOF	Phase 2	NA	[5]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 9 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
TLR5	TTCXP8J	Limited	Biomarker	[6]
GP1BA	TTVB0Q9	moderate	Genetic Variation	[7]
ADAMTS13	TTUREBK	Strong	Biomarker	[8]
CLCA1	TT3AF4R	Strong	Biomarker	[9]
F9	TTFEZ5Q	Strong	Biomarker	[10]
GP6	TTTJUVZ	Strong	Altered Expression	[11]
F11	TTDM4ZU	Definitive	Biomarker	[12]
IL11	TTGUYTR	Definitive	Biomarker	[13]
P2RY12	TTZ1DT0	Definitive	Biomarker	[14]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ABO	DESIA7R	Definitive	Biomarker	[15]

This Disease Is Related to 20 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ITIH1	OTSXJGQF	Limited	Biomarker	[16]
ITIH5	OTP46PZM	Limited	Biomarker	[16]
COX8A	OTU0NR39	moderate	Biomarker	[17]
AK3	OTM59ZGG	Strong	Biomarker	[10]
ALKBH1	OTADGU5D	Strong	Genetic Variation	[18]
ANO2	OT650E98	Strong	Genetic Variation	[19]
ANTXR1	OT5W1GPC	Strong	Genetic Variation	[20]
ATP6V0A2	OTJBDX0Y	Strong	Biomarker	[21]
BMPER	OTBYON4H	Strong	Genetic Variation	[22]
CANX	OTYP1F6J	Strong	Genetic Variation	[23]
CHRD	OTNM60Y1	Strong	Genetic Variation	[22]
CLEC4M	OT2WUIIP	Strong	Altered Expression	[24]
COCH	OTBEHD89	Strong	Genetic Variation	[25]
CRISPLD2	OTVSFHTL	Strong	Biomarker	[6]
CSHL1	OTQKU2F5	Strong	Biomarker	[26]
FAM20C	OTW5YZ7X	Strong	Biomarker	[27]
POU2F3	OTIOOJWD	Strong	Genetic Variation	[28]
PRB2	OTAD4JZ0	Strong	Biomarker	[28]
SMPX	OTLSHGBF	Strong	Biomarker	[26]
STXBP5	OTE3M7QB	Strong	Altered Expression	[24]

References

• [1] Desmopressin FDA Label
• [2] Vasopressin FDA Label
• [3] Clinical pipeline report, company report or official report of Vonvendi.
• [4] FcRn Rescues Recombinant Factor VIII Fc Fusion Protein from a VWF Independent FVIII Clearance Pathway in Mouse Hepatocytes. PLoS One. 2015 Apr 23;10(4):e0124930.
• [5] ClinicalTrials.gov (NCT04677803) A Phase 2a Multiple Dose Basket Study of the Safety, Tolerability, and Pharmacologic Activity of BT200 in Patients With Hereditary Bleeding Disorders. U.S.National Institutes of Health.
• [6] The von Willebrand factor D'D3 assembly and structural principles for factor VIII binding and concatemer biogenesis.Blood. 2019 Apr 4;133(14):1523-1533. doi: 10.1182/blood-2018-10-876300. Epub 2019 Jan 14.
• [7] Protein kinase C signaling dysfunction in von Willebrand disease (p.V1316M) type 2B platelets.Blood Adv. 2018 Jun 26;2(12):1417-1428. doi: 10.1182/bloodadvances.2017014290.
• [8] Thrombotic microangiopathy as a cause of cardiovascular toxicity from the BCR-ABL1 tyrosine kinase inhibitor ponatinib.Blood. 2019 Apr 4;133(14):1597-1606. doi: 10.1182/blood-2018-10-881557. Epub 2019 Jan 28.
• [9] Calcium-activated chloride channel regulator 1 (CLCA1) forms non-covalent oligomers in colonic mucus and has mucin 2-processing properties.J Biol Chem. 2019 Nov 8;294(45):17075-17089. doi: 10.1074/jbc.RA119.009940. Epub 2019 Sep 29.
• [10] High proportion of patients with bleeding of unknown cause in persons with a mild-to-moderate bleeding tendency: Results from the Vienna Bleeding Biobank (VIBB).Haemophilia. 2018 May;24(3):405-413. doi: 10.1111/hae.13422. Epub 2018 Feb 1.
• [11] Platelet membrane glycoprotein polymorphisms do not influence the clinical expressivity of von Willebrand disease type 1.Thromb Haemost. 2003 Dec;90(6):1135-40. doi: 10.1160/TH03-03-0135.
• [12] Rapid Centrifugation in the Routine Hemostasis Laboratory.Thromb Haemost. 2019 Dec;119(12):2025-2033. doi: 10.1055/s-0039-1696712. Epub 2019 Oct 10.
• [13] Phase II prospective open-label trial of recombinant interleukin-11 in desmopressin-unresponsive von Willebrand disease and mild or moderate haemophilia A.Thromb Haemost. 2013 Feb;109(2):248-54. doi: 10.1160/TH12-06-0447. Epub 2012 Dec 13.
• [14] P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries.J Clin Invest. 2003 Aug;112(3):398-406. doi: 10.1172/JCI17864.
• [15] Influence of ABO blood group on von Willebrand factor tests in healthy Saudi blood donors.Blood Coagul Fibrinolysis. 2018 Mar;29(2):211-215. doi: 10.1097/MBC.0000000000000709.
• [16] Decreased ITIH5 expression is associated with poor prognosis in primary gastric cancer.Med Oncol. 2014 Jul;31(7):53. doi: 10.1007/s12032-014-0053-1. Epub 2014 Jun 10.
• [17] FranceCoag: a 22-year prospective follow-up of the national French cohort of patients with inherited bleeding disorders.Eur J Epidemiol. 2019 May;34(5):521-532. doi: 10.1007/s10654-018-0468-7. Epub 2018 Dec 5.
• [18] No evidence for a direct effect of von Willebrand factor's ABH blood group antigens on von Willebrand factor clearance.J Thromb Haemost. 2015 Apr;13(4):592-600. doi: 10.1111/jth.12867. Epub 2015 Mar 11.
• [19] A common 253-kb deletion involving VWF and TMEM16B in German and Italian patients with severe von Willebrand disease type 3.J Thromb Haemost. 2007 Apr;5(4):722-8. doi: 10.1111/j.1538-7836.2007.02460.x. Epub 2007 Feb 26.
• [20] Molecular Adjuvants Based on Plasmids Encoding Protein Aggregation Domains Affect Bone Marrow Niche Homeostasis.Curr Gene Ther. 2018 Feb 1;17(5):391-397. doi: 10.2174/1566523218666180105122626.
• [21] ATP6V0A2-related cutis laxa in 10 novel patients: Focus on clinical variability and expansion of the phenotype.Exp Dermatol. 2019 Oct;28(10):1142-1145. doi: 10.1111/exd.13723. Epub 2018 Aug 20.
• [22] Thrombospondin-1 (TSP-1), a new bone morphogenetic protein-2 and -4 (BMP-2/4) antagonist identified in pituitary cells.J Biol Chem. 2017 Sep 15;292(37):15352-15368. doi: 10.1074/jbc.M116.736207. Epub 2017 Jul 26.
• [23] Endoplasmic reticulum retention and prolonged association of a von Willebrand's disease-causing von Willebrand factor variant with ERp57 and calnexin.Biochem Biophys Res Commun. 2001 Jan 19;280(2):448-53. doi: 10.1006/bbrc.2000.4139.
• [24] CLEC4M and STXBP5 gene variations contribute to von Willebrand factor level variation in von Willebrand disease.J Thromb Haemost. 2015 Jun;13(6):956-66. doi: 10.1111/jth.12927. Epub 2015 May 9.
• [25] The second von Willebrand type A domain of cochlin has high affinity for type I, type II and type IV collagens.FEBS Lett. 2008 Dec 10;582(29):4003-7. doi: 10.1016/j.febslet.2008.10.050. Epub 2008 Nov 12.
• [26] Pharmacokinetics, efficacy, and safety of a plasma-derived VWF/FVIII concentrate (VONCENTO) for on-demand and prophylactic treatment in patients with von Willebrand disease (SWIFT-VWD study).Blood Coagul Fibrinolysis. 2017 Mar;28(2):152-162. doi: 10.1097/MBC.0000000000000568.
• [27] In vitro phosphorylation of von Willebrand factor by FAM20c enhances its ability to support platelet adhesion.J Thromb Haemost. 2019 Jun;17(6):866-877. doi: 10.1111/jth.14426. Epub 2019 Apr 5.
• [28] Impact of thrombogenic mutations on clinical phenotypes of von Willebrand disease.Clin Appl Thromb Hemost. 2010 Jun;16(3):281-7. doi: 10.1177/1076029609351291. Epub 2009 Dec 2.