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Complete plasminogen activator inhibitor 1 deficiency

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Description

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.

Frequency

Complete PAI-1 deficiency is a rare disorder; its prevalence is unknown. It has been well studied in a large family belonging to the Old Order Amish population of eastern and southern Indiana. Additional cases in North America, Europe, and Asia have been described in the medical literature.

Complete PAI-1 deficiency is inherited equally by both sexes, but tends to be diagnosed earlier and more frequently in females because of its effects on menstruation, pregnancy, and childbirth.

Causes

Complete PAI-1 deficiency is caused by mutations in the SERPINE1 gene. This gene provides instructions for making a protein called plasminogen activator inhibitor 1 (PAI-1). PAI-1 is involved in normal blood clotting (hemostasis). After an injury, clots protect the body by sealing off damaged blood vessels and preventing further blood loss.

The PAI-1 protein blocks (inhibits) the action of other proteins called plasminogen activators. These proteins promote the dissolution of clots (fibrinolysis). By inhibiting plasminogen activators, the PAI-1 protein helps ensure that clots remain intact until they are no longer needed to stop bleeding.

The SERPINE1 gene mutations that cause complete PAI-1 deficiency result in the production of a PAI-1 protein that is nonfunctional or that is unstable and quickly broken down. Absence of functional PAI-1 protein allows plasminogen activators to dissolve blood clots prematurely, resulting in the abnormal bleeding associated with this disorder.

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Other Names for This Condition

  • complete PAI-1 deficiency
  • congenital plasminogen activator inhibitor type 1 deficiency
  • homozygous PAI-1 deficiency
  • hyperfibrinolysis due to PAI1 deficiency
  • PAI-1 deficiency
  • PAI-1D
  • PAI1 deficiency
  • plasminogen activator inhibitor type 1 deficiency
  • plasminogen inhibitor-1 deficiency
  • quantitative PAI-1 deficiency

Additional Information & Resources

Genetic and Rare Diseases Information Center

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • Fay WP, Parker AC, Condrey LR, Shapiro AD. Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene. Blood. 1997 Jul 1;90(1):204-8. Citation on PubMed
  • Flevaris P, Vaughan D. The Role of Plasminogen Activator Inhibitor Type-1 in Fibrosis. Semin Thromb Hemost. 2017 Mar;43(2):169-177. doi: 10.1055/s-0036-1586228. Epub 2016 Aug 24. Review. Citation on PubMed
  • Heiman M, Gupta S, Khan SS, Vaughan DE, Shapiro AD. Complete Plasminogen Activator Inhibitor 1 Deficiency. 2017 Aug 3. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK447152/ Citation on PubMed
  • Heiman M, Gupta S, Shapiro AD. The obstetric, gynaecological and fertility implications of homozygous PAI-1 deficiency: single-centre experience. Haemophilia. 2014 May;20(3):407-12. doi: 10.1111/hae.12313. Epub 2013 Nov 22. Citation on PubMed
  • Jankun J, Skrzypczak-Jankun E. Plasminogen activator inhibitor with very long half-life (VLHL PAI-1) can reduce bleeding in PAI-1-deficient patients. Cardiovasc Hematol Disord Drug Targets. 2013 Aug;13(2):144-50. Review. Citation on PubMed
  • Mehta R, Shapiro AD. Plasminogen activator inhibitor type 1 deficiency. Haemophilia. 2008 Nov;14(6):1255-60. doi: 10.1111/j.1365-2516.2008.01834.x. Review. Citation on PubMed
  • Minowa H, Takahashi Y, Tanaka T, Naganuma K, Ida S, Maki I, Yoshioka A. Four cases of bleeding diathesis in children due to congenital plasminogen activator inhibitor-1 deficiency. Haemostasis. 1999;29(5):286-91. Citation on PubMed
  • Takahashi Y, Tanaka T, Minowa H, Ookubo Y, Sugimoto M, Nakajima M, Miyauchi Y, Yoshioka A. Hereditary partial deficiency of plasminogen activator inhibitor-1 associated with a lifelong bleeding tendency. Int J Hematol. 1996 Jul;64(1):61-8. Citation on PubMed
  • Yasar Yildiz S, Kuru P, Toksoy Oner E, Agirbasli M. Functional stability of plasminogen activator inhibitor-1. ScientificWorldJournal. 2014;2014:858293. doi: 10.1155/2014/858293. Epub 2014 Oct 15. Review. Citation on PubMed or Free article on PubMed Central
  • Zhang ZY, Wang ZY, Dong NZ, Bai X, Zhang W, Ruan CG. A case of deficiency of plasma plasminogen activator inhibitor-1 related to Ala15Thr mutation in its signal peptide. Blood Coagul Fibrinolysis. 2005 Jan;16(1):79-84. Citation on PubMed
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