VWD3
MCID: VNW008
MIFTS: 50

Von Willebrand Disease, Type 3 (VWD3)

Categories: Blood diseases, Cardiovascular diseases, Genetic diseases, Immune diseases, Rare diseases, Smell/Taste diseases

Aliases & Classifications for Von Willebrand Disease, Type 3

MalaCards integrated aliases for Von Willebrand Disease, Type 3:

Name: Von Willebrand Disease, Type 3 58 45 41 74
Von Willebrand Disease Type 3 12 60 30 6
Vwd3 58 12 76
Von Willebrand Disease, Recessive Form 30 6
Von Willebrand Disease Type Iii 12 76
Von Willibrand Disease, Type 3 58 13
Von Willebrand's Disease 3 12 15
Von Willebrand Factor Deficiency Type 3 76
Von Willebrand Disease Recessive Form 76
Von Willebrand Disease, Type Iii 58
Von Willebrand Disease 3 76
Vwd, Type 3 58
Vwd Type 3 12

Characteristics:

Orphanet epidemiological data:

60
von willebrand disease type 3
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
most severe type of von willebrand disease


HPO:

33
von willebrand disease, type 3:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0111054
OMIM 58 277480
MeSH 45 D056729
NCIt 51 C85213
MESH via Orphanet 46 D056729
ICD10 via Orphanet 35 D68.0
UMLS via Orphanet 75 C1264041
Orphanet 60 ORPHA166096
UMLS 74 C1264041

Summaries for Von Willebrand Disease, Type 3

OMIM : 58 Von Willebrand disease is a bleeding disorder resulting from a defect in platelet aggregation due to defects in the von Willebrand factor protein. Type 3 von Willebrand disease, which is inherited as an autosomal recessive disorder, is associated with a severe quantitative defect or virtual absence of VWF in plasma, a prolonged bleeding time, and more severe bleeding tendencies compared to the other types of VWD. Type 3 accounts for about 1% of patients with VWD. Bleeding usually starts in infancy and can include epistaxis, recurrent mucocutaneous bleeding, bleeding after surgery, and hemarthroses. Since VWF also serves as a carrier protein for coagulation factor VIII (F8; 300841), affected individuals also have very low levels of plasma F8, resembling hemophilia A (306700) (summary by 24,21:Zhang et al., 1992, 1993; reviews by Sadler et al., 2006 and Lillicrap, 2009). For a general description and a classification of the types of von Willebrand disease, see VWD type 1 (193400). (277480)

MalaCards based summary : Von Willebrand Disease, Type 3, also known as von willebrand disease type 3, is related to hemophilia and factor viii deficiency. An important gene associated with Von Willebrand Disease, Type 3 is VWF (Von Willebrand Factor), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and ECM-receptor interaction. The drugs Factor VIII and Coagulants have been mentioned in the context of this disorder. Affiliated tissues include endothelial, and related phenotypes are joint hemorrhage and thrombocytopenia

Disease Ontology : 12 A von Willebrand's disease characterized by autosomal recessive inheritance of a severe quantitative defect or virtual absence of VWF in plasma, prolonged bleeding time, and more severe bleeding tendencies compared to the other types of von Willebrand disease that has material basis in homozygous or compound heterozygous mutation in the VWF gene which maps to chromosome 12p13.

UniProtKB/Swiss-Prot : 76 von Willebrand disease 3: A severe hemorrhagic disorder due to a total or near total absence of von Willebrand factor in the plasma and cellular compartments, also leading to a profound deficiency of plasmatic factor VIII. Bleeding usually starts in infancy and can include epistaxis, recurrent mucocutaneous bleeding, excessive bleeding after minor trauma, and hemarthroses.

Related Diseases for Von Willebrand Disease, Type 3

Diseases in the Von Willebrand's Disease family:

Pseudo-Von Willebrand Disease Von Willebrand Disease, Type 1
Von Willebrand Disease, Type 3 Von Willebrand Disease, Type 2
Acquired Von Willebrand Syndrome

Diseases related to Von Willebrand Disease, Type 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 66)
# Related Disease Score Top Affiliating Genes
1 hemophilia 30.4 F3 F8 VWF
2 factor viii deficiency 30.4 F11 F8 VWF
3 thrombophilia due to thrombin defect 30.4 F3 F8 VWF
4 von willebrand disease, type 1 30.4 F3 F8 GP6 VWF
5 von willebrand's disease 30.3 ANO2 F11 F3 F8 GP1BA SELP
6 hemophilia a 30.1 F11 F3 F8 VWF
7 thrombosis 29.5 F3 F8 GP1BA GP6 SELP VWF
8 fainting 10.4 F8 VWF
9 cerebral arteritis 10.4 F8 VWF
10 brachydactyly, type d 10.4 F8 VWF
11 hemarthrosis 10.4 F8 VWF
12 pseudo-von willebrand disease 10.3 GP1BA VWF
13 fournier gangrene 10.3 F3 F8
14 korean hemorrhagic fever 10.3 F3 VWF
15 factor xiii deficiency 10.3 F3 F8
16 platelet aggregation, spontaneous 10.3 SELP VWF
17 hepatic vascular disease 10.3 F3 VWF
18 lymphangiosarcoma 10.2 F8 VWF
19 intracranial thrombosis 10.2 F3 F8 VWF
20 thrombophilia due to activated protein c resistance 10.2 F3 F8 VWF
21 drug-induced lupus erythematosus 10.2 MCAM VWF
22 lemierre's syndrome 10.2 F11 F3
23 carotid artery thrombosis 10.2 F3 SELP
24 acquired hemophilia 10.2 F11 F3 F8
25 acquired hemophilia a 10.2 F11 F3 F8
26 alcohol-related birth defect 10.2 F11 F3 F8
27 autoimmune disease of blood 10.2 GP1BA SELP VWF
28 factor x deficiency 10.2 F11 F3 VWF
29 hemophilia b 10.2 F11 F3 F8
30 giant hemangioma 10.2 DLL1 F3
31 factor xi deficiency 10.2 F11 F3
32 qualitative platelet defect 10.2 F3 SELP VWF
33 thrombasthenia 10.1 F3 GP1BA SELP
34 grange syndrome 10.1 F3 SELP VWF
35 intermediate coronary syndrome 10.1 F3 SELP VWF
36 thrombotic thrombocytopenic purpura 10.1 F3 SELP VWF
37 vein disease 10.1 F3 F8
38 venous insufficiency 10.1 SELP VWF
39 antiphospholipid syndrome 10.1 F3 SELP VWF
40 bernard-soulier syndrome 10.1 CD9 F8 GP1BA VWF
41 peripheral vascular disease 10.1 F3 SELP VWF
42 arteries, anomalies of 10.1 F3 SELP VWF
43 inherited blood coagulation disease 10.1 F3 F8 GP1BA VWF
44 endocardium disease 10.1 DLL1 F3
45 acquired von willebrand syndrome 10.1 F11 F8 GP1BA VWF
46 gray platelet syndrome 10.1 GP6 SELP VWF
47 acute myocardial infarction 10.1 F3 SELP VWF
48 thrombocytopenic purpura, autoimmune 10.1 GP1BA GP6 SELP
49 arteriosclerosis obliterans 10.1 MCAM SELP
50 afibrinogenemia 10.1 F11 F3 F8 VWF

Graphical network of the top 20 diseases related to Von Willebrand Disease, Type 3:



Diseases related to Von Willebrand Disease, Type 3

Symptoms & Phenotypes for Von Willebrand Disease, Type 3

Human phenotypes related to Von Willebrand Disease, Type 3:

33 (show all 11)
# Description HPO Frequency HPO Source Accession
1 joint hemorrhage 33 occasional (7.5%) HP:0005261
2 thrombocytopenia 33 HP:0001873
3 epistaxis 33 HP:0000421
4 bruising susceptibility 33 HP:0000978
5 prolonged bleeding time 33 HP:0003010
6 menorrhagia 33 HP:0000132
7 prolonged bleeding after surgery 33 HP:0004846
8 persistent bleeding after trauma 33 HP:0001934
9 reduced factor viii activity 33 HP:0003125
10 impaired platelet aggregation 33 HP:0003540
11 reduced von willebrand factor activity 33 HP:0008330

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Nose:
epistaxis

Skin Nails Hair Skin:
easy bruising

Laboratory Abnormalities:
severely decreased antigen levels of vwf and factor viii

Hematology:
prolonged bleeding time
menorrhagia
mucocutaneous bleeding
prolonged bleeding after surgery or trauma

Skeletal:
hemarthrosis may occur

Clinical features from OMIM:

277480

GenomeRNAi Phenotypes related to Von Willebrand Disease, Type 3 according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased vaccinia virus (VACV) infection GR00249-S 9.5 ANO2 ATAT1 CD9 DLL1 F11 F3

MGI Mouse Phenotypes related to Von Willebrand Disease, Type 3:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.7 ATAT1 CD9 DLL1 F11 F3 F8
2 immune system MP:0005387 9.28 CD9 DLL1 F11 F3 F8 GP6

Drugs & Therapeutics for Von Willebrand Disease, Type 3

Drugs for Von Willebrand Disease, Type 3 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 10)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Factor VIII Phase 4,Phase 3,Phase 2,Phase 1
2 Coagulants Phase 4,Phase 3,Phase 2,Phase 1
3 Pharmaceutical Solutions Phase 3
4
Oprelvekin Approved, Investigational Phase 2 145941-26-0
5 Natriuretic Agents Phase 2
6 arginine Phase 2
7 Arginine Vasopressin Phase 2
8 Hemostatics Phase 2
9 Vasopressins Phase 2
10 Deamino Arginine Vasopressin Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Efficacy and Safety of Fanhdi®, a High-purity Von Willebrand Containing FVIII Concentrate, in Pediatric Patients With Von Willebrand Disease Recruiting NCT02472665 Phase 4 plasma-derived FVIII/VWF concentrate
2 Efficacy of Alphanate FVIII/VWF Concentrate in Type 3 Von Willebrand Patients Active, not recruiting NCT00555555 Phase 4
3 Study of Biostate® in Children With Von Willebrand Disease Completed NCT01213446 Phase 3
4 Pharmacokinetics, Safety and Efficacy of Recombinant Von Willebrand Factor (rVWF) in the Treatment of Bleeding Episodes in Von Willebrand Disease (VWD) Completed NCT01410227 Phase 3 Placebo
5 Efficacy and Safety of IL-11 in DDAVP Unresponsive Completed NCT00994929 Phase 2
6 Pharmacokinetic, Safety and Tolerability Study of Recombinant Von Willebrand Factor / Recombinant Factor VIII Complex in Type 3 Von Willebrand Disease Completed NCT00816660 Phase 1
7 Type 3 Von Willebrand International Registries Inhibitor Prospective Study Unknown status NCT02460458

Search NIH Clinical Center for Von Willebrand Disease, Type 3

Cochrane evidence based reviews: von willebrand disease, type 3

Genetic Tests for Von Willebrand Disease, Type 3

Genetic tests related to Von Willebrand Disease, Type 3:

# Genetic test Affiliating Genes
1 Von Willebrand Disease, Recessive Form 30 VWF
2 Von Willebrand Disease Type 3 30

Anatomical Context for Von Willebrand Disease, Type 3

MalaCards organs/tissues related to Von Willebrand Disease, Type 3:

42
Endothelial

Publications for Von Willebrand Disease, Type 3

Articles related to Von Willebrand Disease, Type 3:

(show all 26)
# Title Authors Year
1
Liver transplantation in hemophilia A and von Willebrand disease type 3: perioperative management and post-transplant outcome. ( 29931985 )
2018
2
A 12.3-kb Duplication Within the VWF Gene in Pigs Affected by Von Willebrand Disease Type 3. ( 29208651 )
2018
3
Monitoring of coagulation factor therapy in patients with von Willebrand disease type 3 using a microchip flow chamber system. ( 27761577 )
2017
4
Phenotypic and genotypic characterization of 10 Finnish patients with von Willebrand disease type 3: discovery of two main mutations. ( 23834637 )
2013
5
Management of von Willebrand disease type 3 during pregnancy - 2 cases reports. ( 24254552 )
2013
6
Current management of patients with severe von Willebrand disease type 3: a 2012 update. ( 22722677 )
2012
7
An unexpected transmission of von Willebrand disease type 3: the first case of maternal uniparental disomy 12. ( 21750090 )
2011
8
Platelet morphological changes in 2 patients with von Willebrand disease type 3 caused by large homozygous deletions of the von Willebrand factor gene. ( 19608674 )
2009
9
A novel deletion mutation is recurrent in von Willebrand disease types 1 and 3. ( 19372260 )
2009
10
Genetic defects in von Willebrand disease type 3 in Indian and Greek patients. ( 18485763 )
2008
11
Clinical and molecular markers of inherited von Willebrand disease type 3: are deletions of the VWF gene associated with alloantibodies to VWF? ( 18853484 )
2008
12
A common 253-kb deletion involving VWF and TMEM16B in German and Italian patients with severe von Willebrand disease type 3. ( 17371490 )
2007
13
Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral vectors expressing von Willebrand factor. ( 16478886 )
2006
14
Prophylaxis and treatment of bleeding complications in von Willebrand disease type 3. ( 16977572 )
2006
15
Intracranial hemorrhage in a term newborn with severe von Willebrand disease type 3 associated with sinus venous thrombosis. ( 17194666 )
2006
16
Homozygous C2362F von Willebrand factor induces intracellular retention of mutant von Willebrand factor resulting in autosomal recessive severe von Willebrand disease. ( 16643449 )
2006
17
Congenital von Willebrand disease type 3: clinical manifestations, pathophysiology and molecular biology. ( 11686105 )
2001
18
Continuous infusion of von Willebrand factor and factor VIII after elective heart surgery in a 12-year-old girl with von Willebrand disease type 3. ( 10599096 )
1999
19
Pharmacokinetics of von Willebrand factor and factor VIII coagulant activity in patients with von Willebrand disease type 3 and type 2. ( 10028318 )
1998
20
Characterization of the genetic defects in recessive type 1 and type 3 von Willebrand disease patients of Italian origin. ( 9569178 )
1998
21
Pharmacokinetics of von Willebrand factor and factor VIIIC in patients with severe von Willebrand disease (type 3 VWD): estimation of the rate of factor VIIIC synthesis. Cooperative Study Groups. ( 8826903 )
1996
22
Mutations of von Willebrand factor gene in families with von Willebrand disease in the Aland Islands. ( 8367445 )
1993
23
Delta C in exon 18 of the von Willebrand gene is uncommon in German vWD type III patients. ( 8165603 )
1993
24
Identification of a new nonsense mutation in the von Willebrand factor gene in patients with von Willebrand disease type III. ( 1301136 )
1992
25
Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I. ( 1415226 )
1992
26
A single cytosine deletion in exon 18 of the von Willebrand factor gene is the most common mutation in Swedish vWD type III patients. ( 1302613 )
1992

Variations for Von Willebrand Disease, Type 3

UniProtKB/Swiss-Prot genetic disease variations for Von Willebrand Disease, Type 3:

76
# Symbol AA change Variation ID SNP ID
1 VWF p.Trp377Cys VAR_005782 rs62643626
2 VWF p.Cys2739Tyr VAR_005821 rs61751305
3 VWF p.Pro2063Ser VAR_009142 rs61750615
4 VWF p.Cys2362Phe VAR_009143 rs61750630
5 VWF p.Asn2546Tyr VAR_009144 rs61751298
6 VWF p.Arg273Trp VAR_010242 rs61753997

ClinVar genetic disease variations for Von Willebrand Disease, Type 3:

6 (show all 25)
# Gene Variation Type Significance SNP ID Assembly Location
1 VWF NM_000552.4(VWF): c.2561G> A (p.Arg854Gln) single nucleotide variant Pathogenic rs41276738 GRCh37 Chromosome 12, 6143978: 6143978
2 VWF NM_000552.4(VWF): c.2561G> A (p.Arg854Gln) single nucleotide variant Pathogenic rs41276738 GRCh38 Chromosome 12, 6034812: 6034812
3 VWF NM_000552.4(VWF): c.4975C> T (p.Arg1659Ter) single nucleotide variant Pathogenic rs61750595 GRCh37 Chromosome 12, 6127609: 6127609
4 VWF NM_000552.4(VWF): c.4975C> T (p.Arg1659Ter) single nucleotide variant Pathogenic rs61750595 GRCh38 Chromosome 12, 6018443: 6018443
5 VWF NM_000552.4(VWF): c.5557C> T (p.Arg1853Ter) single nucleotide variant Pathogenic rs61750612 GRCh37 Chromosome 12, 6122710: 6122710
6 VWF NM_000552.4(VWF): c.5557C> T (p.Arg1853Ter) single nucleotide variant Pathogenic rs61750612 GRCh38 Chromosome 12, 6013544: 6013544
7 VWF NM_000552.4(VWF): c.7603C> T (p.Arg2535Ter) single nucleotide variant Pathogenic rs61751296 GRCh37 Chromosome 12, 6078503: 6078503
8 VWF NM_000552.4(VWF): c.7603C> T (p.Arg2535Ter) single nucleotide variant Pathogenic rs61751296 GRCh38 Chromosome 12, 5969337: 5969337
9 VWF NM_000552.4(VWF): c.2435del (p.Pro812Argfs) deletion Pathogenic rs62643632 GRCh38 Chromosome 12, 6044298: 6044298
10 VWF NM_000552.4(VWF): c.2435del (p.Pro812Argfs) deletion Pathogenic rs62643632 GRCh37 Chromosome 12, 6153464: 6153464
11 VWF NM_000552.4(VWF): c.7085G> T (p.Cys2362Phe) single nucleotide variant Pathogenic rs61750630 GRCh37 Chromosome 12, 6091154: 6091154
12 VWF NM_000552.4(VWF): c.7085G> T (p.Cys2362Phe) single nucleotide variant Pathogenic rs61750630 GRCh38 Chromosome 12, 5981988: 5981988
13 VWF VWF, 8.6-KB DEL, EX4-5 deletion Pathogenic
14 VWF NM_000552.4(VWF): c.1922C> T (p.Ala641Val) single nucleotide variant Uncertain significance rs61754019 GRCh37 Chromosome 12, 6166046: 6166046
15 VWF NM_000552.4(VWF): c.1922C> T (p.Ala641Val) single nucleotide variant Uncertain significance rs61754019 GRCh38 Chromosome 12, 6056880: 6056880
16 VWF NM_000552.4(VWF): c.6859C> T (p.Arg2287Trp) single nucleotide variant Uncertain significance rs61750625 GRCh37 Chromosome 12, 6094771: 6094771
17 VWF NM_000552.4(VWF): c.6859C> T (p.Arg2287Trp) single nucleotide variant Uncertain significance rs61750625 GRCh38 Chromosome 12, 5985605: 5985605
18 VWF NM_000552.4(VWF): c.7940C> T (p.Thr2647Met) single nucleotide variant Uncertain significance rs61751302 GRCh37 Chromosome 12, 6062708: 6062708
19 VWF NM_000552.4(VWF): c.7940C> T (p.Thr2647Met) single nucleotide variant Uncertain significance rs61751302 GRCh38 Chromosome 12, 5953542: 5953542
20 VWF NM_000552.4(VWF): c.1625C> G (p.Ala542Gly) single nucleotide variant Uncertain significance rs141649383 GRCh37 Chromosome 12, 6167119: 6167119
21 VWF NM_000552.4(VWF): c.1625C> G (p.Ala542Gly) single nucleotide variant Uncertain significance rs141649383 GRCh38 Chromosome 12, 6057953: 6057953
22 VWF NM_000552.4(VWF): c.2570A> G (p.Asn857Ser) single nucleotide variant Uncertain significance rs765163545 GRCh37 Chromosome 12, 6143969: 6143969
23 VWF NM_000552.4(VWF): c.2570A> G (p.Asn857Ser) single nucleotide variant Uncertain significance rs765163545 GRCh38 Chromosome 12, 6034803: 6034803
24 VWF NM_000552.4(VWF): c.5851A> G (p.Thr1951Ala) single nucleotide variant Uncertain significance rs144072210 GRCh37 Chromosome 12, 6105380: 6105380
25 VWF NM_000552.4(VWF): c.5851A> G (p.Thr1951Ala) single nucleotide variant Uncertain significance rs144072210 GRCh38 Chromosome 12, 5996214: 5996214

Expression for Von Willebrand Disease, Type 3

Search GEO for disease gene expression data for Von Willebrand Disease, Type 3.

Pathways for Von Willebrand Disease, Type 3

GO Terms for Von Willebrand Disease, Type 3

Cellular components related to Von Willebrand Disease, Type 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 9.85 ANO2 CD9 DLL1 F11 F3 F8
2 extracellular space GO:0005615 9.17 CD9 F11 F3 F8 GP1BA MCAM
3 platelet alpha granule membrane GO:0031092 8.96 CD9 SELP

Biological processes related to Von Willebrand Disease, Type 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell adhesion GO:0007155 9.77 CD9 GP1BA MCAM SELP VWF
2 platelet activation GO:0030168 9.65 CD9 F8 GP1BA GP6 VWF
3 blood coagulation GO:0007596 9.63 F11 F3 F8 GP1BA GP6 VWF
4 platelet degranulation GO:0002576 9.62 CD9 F8 SELP VWF
5 regulation of blood coagulation GO:0030193 9.4 F11 GP1BA
6 blood coagulation, intrinsic pathway GO:0007597 9.26 F11 F8 GP1BA VWF
7 hemostasis GO:0007599 9.1 F11 F3 F8 GP1BA GP6 VWF

Sources for Von Willebrand Disease, Type 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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