MCID: PLS029
MIFTS: 41

Plasminogen Activator Inhibitor-1 Deficiency

Categories: Genetic diseases, Rare diseases, Blood diseases

Aliases & Classifications for Plasminogen Activator Inhibitor-1 Deficiency

MalaCards integrated aliases for Plasminogen Activator Inhibitor-1 Deficiency:

Name: Plasminogen Activator Inhibitor-1 Deficiency 53 71 13 69
Plasminogen Activator Inhibitor Type 1 Deficiency 49 28
Hyperfibrinolysis Due to Pai1 Deficiency 53 49
Congenital Plasminogen Activator Inhibitor Type 1 Deficiency 55
Plasminogen Activator Inhibitor Type 1 Deficiency 36
Plasminogen Activator Inhibitor 1 Deficiency 49
Plasminogen Activator Inhibitor, Type I 13
Congenital Pai-1 Deficiency 55
Pai-1 Deficiency 49
Pai1 Deficiency 49
Pai-1d 71

Characteristics:

Orphanet epidemiological data:

55
congenital plasminogen activator inhibitor type 1 deficiency
Inheritance: Autosomal recessive; Age of onset: Adolescent,Adult,Childhood,Infancy; Age of death: any age;

OMIM:

53
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
congenital onset
spontaneous bleeding is rare
favorable management with the fibrinolysis inhibitors (e.g., epsilon-aminocaproic acid and tranexamic acid)


HPO:

31
plasminogen activator inhibitor-1 deficiency:
Inheritance autosomal dominant inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



External Ids:

OMIM 53 613329
Orphanet 55 ORPHA465
UMLS via Orphanet 70 C2750067
ICD10 via Orphanet 33 D68.8
MedGen 39 C2750067
MeSH 41 D025861
KEGG 36 H01106
SNOMED-CT via HPO 65 263681008 258211005 386692008
UMLS 69 C2750067

Summaries for Plasminogen Activator Inhibitor-1 Deficiency

NIH Rare Diseases : 49 Plasminogen activator inhibitor type 1 (PAI1) deficiency is a rare bleeding disorder that causes excessive or prolonged bleeding due to blood clots being broken down too early. PAI1 is a protein in the body needed for normal blood clotting. When the body does not have enough functional PAI1, the body's ability keep blood clots intact is impaired. Some people with PAI1 deficiency have some functional PAI1 (partial PAI1 deficiency), while others do not have any (complete PAI1 deficiency). Therefore, the severity of symptoms depends on how much functional PAI1 a person has. People with complete PAI1 deficiency may have symptoms in infancy, while those with partial PAI1 deficiency may not have symptoms until later in life, after an injury or surgery. Symptoms of PAI1 deficiency include excessive or prolonged bleeding after an injury, or after a medical or dental procedure. The bleeding may be delayed if clots initially form but are broken down too early. Internal bleeding after an injury can be life-threatening, particularly if it occurs around the brain. Other symptoms may include delayed wound healing, nosebleeds that last a long time, easy bruising, bleeding in the joints, and excessive bleeding in females during menstruation, pregnancy or childbirth. Some people with PAI1 deficiency may have scar tissue in the heart (cardiac fibrosis). PAI1 deficiency is caused by mutations in the SERPINE1 gene and inheritance typically is autosomal recessive. The specific mutations present determine whether a person has complete or partial PAI1 deficiency. In rare cases partial PAI1 deficiency has appeared to be autosomal dominant, but the genetic causes in these cases were not determined. In general, people with one SERPINE1 mutation (carriers) will not develop significant symptoms, if any. A diagnosis of PAI1 deficiency may be made based on evaluation of symptoms, various blood tests, and genetic testing of the SERPINE1 gene. Treatment for severe bleeding episodes may include intravenous antifibrinolytics (drugs that help the blood clot) and infusion of fresh frozen plasma. Antifibrinolytics may also be used for heavy menstrual bleeding or to prevent bleeding during an invasive procedure or childbirth. Last updated: 1/5/2018

MalaCards based summary : Plasminogen Activator Inhibitor-1 Deficiency, also known as plasminogen activator inhibitor type 1 deficiency, is related to acute myocardial infarction and myocardial infarction, and has symptoms including menorrhagia An important gene associated with Plasminogen Activator Inhibitor-1 Deficiency is SERPINE1 (Serpin Family E Member 1), and among its related pathways/superpathways are p53 signaling pathway and Complement and coagulation cascades. Affiliated tissues include testes, brain and heart.

OMIM : 53 Plasminogen inhibitor-1 deficiency is a rare autosomal recessive hematologic disorder characterized by increased bleeding after trauma, injury, or surgery. Affected females have menorrhagia. The bleeding defect is due to increased fibrinolysis of fibrin blood clots due to deficiency of PAI1, which inhibits tissue (PLAT; 173370) and urinary (PLAU; 191840) activators of plasminogen (PLG; 173350) (review by Mehta and Shapiro, 2008). (613329)

UniProtKB/Swiss-Prot : 71 Plasminogen activator inhibitor-1 deficiency: A hematologic disorder characterized by increased bleeding after trauma, injury, or surgery. Affected females have menorrhagia. The bleeding defect is due to increased fibrinolysis of fibrin blood clots due to deficiency of plasminogen activator inhibitor-1, which inhibits tissue and urinary activators of plasminogen.

Wikipedia : 72 Plasminogen activator inhibitor-1 (PAI-1) also known as endothelial plasminogen activator inhibitor or... more...

Related Diseases for Plasminogen Activator Inhibitor-1 Deficiency

Diseases related to Plasminogen Activator Inhibitor-1 Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 60)
# Related Disease Score Top Affiliating Genes
1 acute myocardial infarction 28.8 PLAT SERPINE1 SERPINF2
2 myocardial infarction 28.7 PLAT SERPINE1 SERPINF2
3 complete plasminogen activator inhibitor 1 deficiency 11.4
4 body mass index quantitative trait locus 11 10.0
5 body mass index quantitative trait locus 9 10.0
6 body mass index quantitative trait locus 8 10.0
7 body mass index quantitative trait locus 4 10.0
8 body mass index quantitative trait locus 10 10.0
9 body mass index quantitative trait locus 7 10.0
10 body mass index quantitative trait locus 12 10.0
11 body mass index quantitative trait locus 14 10.0
12 body mass index quantitative trait locus 18 10.0
13 factor xiii deficiency 10.0 SERPINE1 SERPINF2
14 endotheliitis 9.9
15 platelet aggregation, spontaneous 9.8 PLAT SERPINF2
16 intracranial embolism 9.8 PLAT SERPINF2
17 marantic endocarditis 9.8 PLAT SERPINF2
18 fibrosis of extraocular muscles, congenital, 1 9.8
19 brittle bone disorder 9.8
20 osteoarthritis with mild chondrodysplasia 9.8
21 microvascular complications of diabetes 3 9.8
22 microvascular complications of diabetes 4 9.8
23 microvascular complications of diabetes 6 9.8
24 microvascular complications of diabetes 7 9.8
25 osteoarthritis 9.8
26 pneumonia 9.8
27 fibrinolytic defect 9.8 PLAT SERPINE1
28 argentine hemorrhagic fever 9.8 PLAT SERPINE1
29 chordoma 9.8
30 melioidosis 9.8
31 choroiditis 9.8
32 fibrosarcoma 9.8
33 central serous chorioretinopathy 9.8 PLAT SERPINE1
34 carotid artery thrombosis 9.8 PLAT SERPINE1
35 coronary thrombosis 9.7 PLAT SERPINE1
36 chronic venous insufficiency 9.7 PLAT SERPINE1
37 hepatic veno-occlusive disease 9.7 PLAT SERPINE1
38 venous insufficiency 9.7 PLAT SERPINE1
39 thrombophilia due to thrombin defect 9.7 PLAT SERPINE1
40 peripheral vascular disease 9.7 PLAT SERPINE1
41 arteries, anomalies of 9.7 PLAT SERPINE1
42 thrombosis 9.7 PLAT SERPINE1
43 hellp syndrome 9.7 PLAT SERPINE1
44 cerebrovascular disease 9.6 PLAT SERPINE1
45 coronary artery anomaly 9.6 PLAT SERPINE1
46 stroke, ischemic 9.6 PLAT SERPINE1
47 vascular disease 9.6 PLAT SERPINE1
48 hypertension, essential 9.5 PLAT SERPINE1
49 pulmonary hypertension 9.4 PLAT SERPINE1
50 angina pectoris 9.4 PLAT SERPINE1 SERPINF2

Graphical network of the top 20 diseases related to Plasminogen Activator Inhibitor-1 Deficiency:



Diseases related to Plasminogen Activator Inhibitor-1 Deficiency

Symptoms & Phenotypes for Plasminogen Activator Inhibitor-1 Deficiency

Symptoms via clinical synopsis from OMIM:

53
Hematology:
increased bleeding after trauma, surgery, or injury
hematomas after trauma or injury
bleeding defect due to decreased plasminogen activator inhibitor-1
decreased euglobin lysis time
increased fibrinolysis
more

Clinical features from OMIM:

613329

Human phenotypes related to Plasminogen Activator Inhibitor-1 Deficiency:

31
# Description HPO Frequency HPO Source Accession
1 menorrhagia 31 HP:0000132

Drugs & Therapeutics for Plasminogen Activator Inhibitor-1 Deficiency

Search Clinical Trials , NIH Clinical Center for Plasminogen Activator Inhibitor-1 Deficiency

Genetic Tests for Plasminogen Activator Inhibitor-1 Deficiency

Genetic tests related to Plasminogen Activator Inhibitor-1 Deficiency:

# Genetic test Affiliating Genes
1 Plasminogen Activator Inhibitor Type 1 Deficiency 28 SERPINE1

Anatomical Context for Plasminogen Activator Inhibitor-1 Deficiency

MalaCards organs/tissues related to Plasminogen Activator Inhibitor-1 Deficiency:

38
Testes, Brain, Heart, Endothelial, Lung, Bone, Smooth Muscle

Publications for Plasminogen Activator Inhibitor-1 Deficiency

Articles related to Plasminogen Activator Inhibitor-1 Deficiency:

(show all 18)
# Title Authors Year
1
Plasminogen activator inhibitor-1 deficiency enhances subchondral osteopenia after induction of osteoarthritis in mice. ( 28893232 )
2017
2
Organizing empyema induced in mice by Streptococcus pneumoniae: effects of plasminogen activator inhibitor-1 deficiency. ( 27271877 )
2016
3
High-fat Diet Enhances and Plasminogen Activator Inhibitor-1 Deficiency Attenuates Bone Loss in Mice with Lewis Lung Carcinoma. ( 26124329 )
2015
4
Plasminogen activator inhibitor-1 deficiency ameliorates insulin resistance and hyperlipidemia but not bone loss in obese female mice. ( 24605827 )
2014
5
Plasminogen activator inhibitor-1 deficiency augments visceral mesothelial organization, intrapleural coagulation, and lung restriction in mice with carbon black/bleomycin-induced pleural injury. ( 24024554 )
2014
6
Life-threatening hemorrhage and prolonged wound healing are remarkable phenotypes manifested by complete plasminogen activator inhibitor-1 deficiency in humans. ( 21486382 )
2011
7
Intraparenchymal hemorrhage in a patient with osteogenesis imperfecta and plasminogen activator inhibitor-1 deficiency. ( 20142533 )
2010
8
Neither fibrin nor plasminogen activator inhibitor-1 deficiency protects lung function in a mouse model of acute lung injury. ( 19060228 )
2009
9
Plasminogen activator inhibitor-1 deficiency has renal benefits but some adverse systemic consequences in diabetic mice. ( 16735799 )
2006
10
Plasminogen activator inhibitor-1 deficiency protects against aldosterone-induced glomerular injury. ( 16528256 )
2006
11
Effect of plasminogen activator inhibitor-1 deficiency on nutritionally-induced obesity in mice. ( 15886793 )
2005
12
Plasminogen activator inhibitor-1 deficiency retards diabetic nephropathy. ( 15780082 )
2005
13
Plasminogen activator inhibitor-1 deficiency enhances flow-induced smooth muscle cell migration. ( 15262486 )
2004
14
[Report of a case of congenital plasminogen activator inhibitor-1 deficiency]. ( 15182577 )
2004
15
[Anesthetic management of a patient with congenital plasminogen activator inhibitor-1 deficiency]. ( 12632627 )
2003
16
Plasminogen activator inhibitor-1 deficiency prevents hypertension and vascular fibrosis in response to long-term nitric oxide synthase inhibition. ( 11502712 )
2001
17
Plasminogen activator inhibitor-1 deficiency protects against atherosclerosis progression in the mouse carotid artery. ( 11110693 )
2000
18
Four cases of bleeding diathesis in children due to congenital plasminogen activator inhibitor-1 deficiency. ( 10754381 )
1999

Variations for Plasminogen Activator Inhibitor-1 Deficiency

ClinVar genetic disease variations for Plasminogen Activator Inhibitor-1 Deficiency:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 SERPINE1 SERPINE1, 2-BP INS, 4977TA insertion Pathogenic
2 SERPINE1 NM_000602.4(SERPINE1): c.356dup (p.Ile120Aspfs) duplication Pathogenic GRCh37 Chromosome 7, 100773786: 100773786
3 SERPINE1 NM_000602.4(SERPINE1): c.699_700dup (p.Thr234Ilefs) duplication Pathogenic GRCh38 Chromosome 7, 101132068: 101132069

Expression for Plasminogen Activator Inhibitor-1 Deficiency

Search GEO for disease gene expression data for Plasminogen Activator Inhibitor-1 Deficiency.

Pathways for Plasminogen Activator Inhibitor-1 Deficiency

Pathways related to Plasminogen Activator Inhibitor-1 Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 p53 signaling pathway hsa04115
2 Complement and coagulation cascades hsa04610

GO Terms for Plasminogen Activator Inhibitor-1 Deficiency

Cellular components related to Plasminogen Activator Inhibitor-1 Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix GO:0031012 9.16 PLAT SERPINE1
2 extracellular space GO:0005615 9.13 PLAT SERPINE1 SERPINF2
3 platelet alpha granule lumen GO:0031093 8.62 SERPINE1 SERPINF2

Biological processes related to Plasminogen Activator Inhibitor-1 Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of endopeptidase activity GO:0010951 9.37 SERPINE1 SERPINF2
2 negative regulation of peptidase activity GO:0010466 9.32 SERPINE1 SERPINF2
3 platelet degranulation GO:0002576 9.26 SERPINE1 SERPINF2
4 negative regulation of fibrinolysis GO:0051918 9.16 SERPINE1 SERPINF2
5 negative regulation of plasminogen activation GO:0010757 8.96 SERPINE1 SERPINF2
6 fibrinolysis GO:0042730 8.8 PLAT SERPINE1 SERPINF2

Molecular functions related to Plasminogen Activator Inhibitor-1 Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 peptidase inhibitor activity GO:0030414 9.16 SERPINE1 SERPINF2
2 protease binding GO:0002020 8.96 SERPINE1 SERPINF2
3 serine-type endopeptidase inhibitor activity GO:0004867 8.62 SERPINE1 SERPINF2

Sources for Plasminogen Activator Inhibitor-1 Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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