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Congenital plasminogen activator inhibitor type 1 deficiency

ORPHA465
Synonym(s) Congenital PAI-1 deficiency
Prevalence Unknown
Inheritance Autosomal dominant
Age of onset Childhood
ICD-10
  • D68.8
OMIM
UMLS -
MeSH -
MedDRA -

Summary

Congenital plasminogen activator inhibitor type 1 (PAI-1) deficiency is a rare genetic bleeding disorder characterized by premature lysis of hemostatic clots and a moderate bleeding tendency.

Prevalence and incidence are unknown. Both partial and total PAI-1 deficiencies are extremely rare disorders. In the Amish community, eighteen homozygous cases with clinical symptoms and more than 100 heterozygous cases without bleeding symptoms have been reported to date.

Clinical signs of congenital PAI-1 deficiency may appear in early infancy. Spontaneous bleeding is rarely observed, whereas easy bruising or moderate hemorrhage of the knees, elbows, nose and gingiva are usually triggered by mild trauma. However, menstrual bleeding may be severe, and prolonged bleeding after surgery is common. Hemorrhage is less frequent and less severe or absent in heterozygous individuals (partial deficiency) and clinical manifestations, if any, may appear late in life after a traumatic or surgical event.

PAI-1 is the physiological inhibitor of tissue-type plasminogen activator (t-PA), the main source of intravascular fibrinolysis. PAI-1 deficiency may be qualitative or quantitative, and in a few patients the protein is present but functionally inactive. Affected patients carry one (heterozygote) or two (homozygote) alleles with a mutation in the SERPINE1 gene (7q22.1), resulting in partial or total antigenic PAI-1 deficiency.

The diagnosis is based on antigenic (ELISA) and functional (plasminogen activator inhibition test) assay of PAI-1. A genotype analysis may be necessary in family studies. Molecular genetic testing confirms the diagnosis.

Differential diagnosis includes acquired PAI-1 deficiency and alpha2-antiplasmin deficiency (see this term).

Both partial and total PAI-1 deficiencies are transmitted as autosomal recessive traits. Genetic counseling should be offered to affected families.

Prompt diagnosis is essential since hemorrhage can be safely and efficiently treated with fibrinolysis inhibitors (epsilon amino-caproic acid or tranexamic acid), avoiding the use of blood and derivatives. Menstruation and pregnancy require special consideration with regard to diagnosis and treatment with antifibrinolytics.

The prognosis is generally good as bleeding can be prevented and controlled with antifibrinolytic treatment.

Expert reviewer(s)

  • Dr Eduardo ANGLES-CANO

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