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Congenital plasminogen activator inhibitor type 1 deficiency

MedGen UID:
412870
Concept ID:
C2750067
Disease or Syndrome
Synonyms: HYPERFIBRINOLYSIS DUE TO PAI1 DEFICIENCY; Plasminogen activator inhibitor type 1 deficiency
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).
 
Gene (location): SERPINE1 (7q22.1)
 
Monarch Initiative: MONDO:0013227
OMIM®: 613329
Orphanet: ORPHA465

Disease characteristics

Untreated complete plasminogen activator inhibitor 1 (PAI-1) deficiency is characterized by mild-to-moderate bleeding, although in some instances bleeding can be life-threatening. Most commonly, delayed bleeding is associated with injury, trauma, or surgery; spontaneous bleeding does not occur. While males and females with complete PAI-1 deficiency are affected equally, females may present more frequently with clinical manifestations or earlier in life than males due to menorrhagia and postpartum hemorrhage. Fewer than ten families with complete PAI-1 deficiency have been reported to date. The incidence of complete PAI-1 deficiency is higher than expected in the genetic isolate of the Old Order Amish population of eastern and southern Indiana due to a pathogenic founder variant. In one family from this Old Order Amish population, seven individuals were diagnosed to have cardiac fibrosis of varying degrees. [from GeneReviews]
Authors:
Meadow Heiman  |  Sweta Gupta  |  Magdalena Lewandowska, et. al.   view full author information

Additional descriptions

From OMIM
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).  http://www.omim.org/entry/613329
From MedlinePlus Genetics
Complete plasminogen activator inhibitor 1 deficiency (complete PAI-1 deficiency) is a disorder that causes abnormal bleeding. In people with this disorder, bleeding associated with injury can be excessive and last longer than usual.

Individuals with complete PAI-1 deficiency may experience prolonged nosebleeds, excessive bleeding after medical or dental procedures, easy bruising, and significant bleeding into the joints or soft tissues after even a minor injury. Internal bleeding after an injury, especially bleeding around the brain (intracranial hemorrhage), can be life-threatening. Affected females may have excessive bleeding associated with menstruation (menorrhagia) and abnormal bleeding in pregnancy and childbirth.

In addition to bleeding problems, some people with complete PAI-1 deficiency develop scar tissue in the heart (cardiac fibrosis), which can lead to heart failure.  https://medlineplus.gov/genetics/condition/complete-plasminogen-activator-inhibitor-1-deficiency

Clinical features

From HPO
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.
Abnormal bleeding
MedGen UID:
264316
Concept ID:
C1458140
Pathologic Function
An abnormal susceptibility to bleeding, often referred to as a bleeding diathesis. A bleeding diathesis may be related to vascular, platelet and coagulation defects.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCongenital plasminogen activator inhibitor type 1 deficiency
Follow this link to review classifications for Congenital plasminogen activator inhibitor type 1 deficiency in Orphanet.

Recent clinical studies

Etiology

Emiroğlu M, Bozkurt B, Emiroğlu HH, Koplay M, Koçak N, Karabağli P
Blood Coagul Fibrinolysis 2023 Oct 1;34(7):456-461. Epub 2023 Jul 27 doi: 10.1097/MBC.0000000000001246. PMID: 37577870
Urano T, Suzuki Y, Iwaki T, Sano H, Honkura N, Castellino FJ
Curr Drug Targets 2019;20(16):1695-1701. doi: 10.2174/1389450120666190715102510. PMID: 31309890Free PMC Article
Grünewald M, Siegemund A, Grünewald A, Konegan A, Koksch M, Griesshammer M
Haemophilia 2002 Nov;8(6):768-75. doi: 10.1046/j.1365-2516.2002.00686.x. PMID: 12410645
Nowak-Göttl U, Kotthoff S, Hagemeyer E, Junker R, Kehl HG, Vielhaber H, Kececioglu D
Thromb Res 2001 Jul 15;103(2):93-101. doi: 10.1016/s0049-3848(01)00281-x. PMID: 11457466
Lau HK, Teitel JM, Cheung T, Kung SK, Garvey MB
Am J Hematol 1993 Dec;44(4):260-5. doi: 10.1002/ajh.2830440408. PMID: 8237997

Diagnosis

Emiroğlu M, Bozkurt B, Emiroğlu HH, Koplay M, Koçak N, Karabağli P
Blood Coagul Fibrinolysis 2023 Oct 1;34(7):456-461. Epub 2023 Jul 27 doi: 10.1097/MBC.0000000000001246. PMID: 37577870
Jain S, Acharya SS
Transfus Apher Sci 2019 Oct;58(5):572-577. Epub 2019 Aug 8 doi: 10.1016/j.transci.2019.08.007. PMID: 31427261
Nowak-Göttl U, Kotthoff S, Hagemeyer E, Junker R, Kehl HG, Vielhaber H, Kececioglu D
Thromb Res 2001 Jul 15;103(2):93-101. doi: 10.1016/s0049-3848(01)00281-x. PMID: 11457466

Therapy

Jain S, Acharya SS
Transfus Apher Sci 2019 Oct;58(5):572-577. Epub 2019 Aug 8 doi: 10.1016/j.transci.2019.08.007. PMID: 31427261
Grünewald M, Siegemund A, Grünewald A, Konegan A, Koksch M, Griesshammer M
Haemophilia 2002 Nov;8(6):768-75. doi: 10.1046/j.1365-2516.2002.00686.x. PMID: 12410645
Nowak-Göttl U, Kotthoff S, Hagemeyer E, Junker R, Kehl HG, Vielhaber H, Kececioglu D
Thromb Res 2001 Jul 15;103(2):93-101. doi: 10.1016/s0049-3848(01)00281-x. PMID: 11457466

Clinical prediction guides

Saes JL, Schols SEM, Betbadal KF, van Geffen M, Verbeek-Knobbe K, Gupta S, Hardesty BM, Shapiro AD, van Heerde WL
Haemophilia 2019 Nov;25(6):1073-1082. Epub 2019 Aug 30 doi: 10.1111/hae.13842. PMID: 31469483Free PMC Article

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