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.

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.

Normal Function

The SERPINE1 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, including urokinase plasminogen activator (u-PA) and tissue type plasminogen activator (t-PA), convert an inactive enzyme called plasminogen to its active form, plasmin. Plasmin is involved in fibrinolysis, which is the process of dissolving blood clots. By inhibiting the conversion of plasminogen to plasmin, and thereby preventing fibrinolysis, the PAI-1 protein helps ensure that clots are only dissolved when they are no longer needed to stop bleeding.

In addition to its role in hemostasis, PAI-1 is also thought to be involved in cell movement (migration) and the breakdown and replacement (remodeling) of body tissues.

Health Conditions Related to Genetic Changes

Complete plasminogen activator inhibitor 1 deficiency

At least three SERPINE1 gene mutations have been identified in people with complete plasminogen activator inhibitor 1 (PAI-1) deficiency, a disorder that causes abnormal bleeding. In people with this disorder, bleeding after an injury can be excessive and last longer than usual. Affected females may have excessive bleeding associated with menstruation (menorrhagia), and abnormal bleeding in pregnancy and childbirth.

The SERPINE1 gene mutations that cause complete PAI-1 deficiency result in impaired production of the PAI-1 protein, or lead to production of 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.

Other Names for This Gene

• endothelial plasminogen activator inhibitor
• PAI
• PAI-1
• PAI1
• PLANH1
• plasminogen activator inhibitor 1 precursor
• serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
• serpin E1
• serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1

Genomic Location

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.

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.