Rare Nephrology News

Disease Profile

Plasminogen activator inhibitor type 1 deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Elderly

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ICD-10

D68.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Plasminogen activator inhibitor 1 deficiency; PAI-1 deficiency; Hyperfibrinolysis due to PAI1 deficiency;

Categories

Blood Diseases; Congenital and Genetic Diseases

Summary

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.[1][2][3] PAI1 is a protein in the body needed for normal blood clotting.[1] 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.[3]

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.[1][2][3] Some people with PAI1 deficiency may have scar tissue in the heart (cardiac fibrosis).[2][4]

PAI1 deficiency is caused by mutations in the SERPINE1 gene and inheritance typically is autosomal recessive.[2][5] 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.[6] In general, people with one SERPINE1 mutation (carriers) will not develop significant symptoms, if any.[2][3][4] A diagnosis of PAI1 deficiency may be made based on evaluation of symptoms, various blood tests, and genetic testing of the SERPINE1 gene.[3][7]

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.[4]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Autosomal recessive inheritance
0000007
Congenital onset
Symptoms present at birth
0003577
Menorrhagia
Abnormally heavy bleeding during menstruation
0000132

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Plasminogen activator inhibitor type 1 deficiency. This website is maintained by the National Library of Medicine.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Plasminogen activator inhibitor type 1 deficiency. Click on the link to view a sample search on this topic.

          References

          1. Fay WP. Thrombotic and hemorrhagic disorders due to abnormal fibrinolysis. UpToDate. Waltham, MA: UpToDate; May 26, 2017; https://www.uptodate.com/contents/thrombotic-and-hemorrhagic-disorders-due-to-abnormal-fibrinolysis.
          2. Complete plasminogen activator inhibitor 1 deficiency. Genetics Home Reference (GHR). October, 2017; https://ghr.nlm.nih.gov/condition/complete-plasminogen-activator-inhibitor-1-deficiency#synonyms.
          3. Anglés-Cano E. Congenital plasminogen activator inhibitor type 1 deficiency. Orphanet. November, 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=465.
          4. Heiman M, Gupta S, Khan SS, Vaughan DE, Shapiro AD. Complete Plasminogen Activator Inhibitor 1 Deficiency. GeneReviews. August 3, 2017; https://www.ncbi.nlm.nih.gov/books/NBK447152/.
          5. Kniffin CL. Plasminogen Activator Inhibitor-1 Deficiency. Online Mendelian Inheritance in Man (OMIM). March 30, 2010; https://omim.org/entry/613329.
          6. 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; 90(1):204-208. https://www.bloodjournal.org/content/bloodjournal/90/1/204.full.pdf?sso-checked=true.
          7. Gupta S, Sealls W, Shapiro A. Plasminogen Activator Inhibitor Type 1 Deficiency. The Rare Coagulation Disorders Resource Room. https://www.rarecoagulationdisorders.org/diseases/plasminogen-activator-inhibitor-type-1-deficiency/disease-overview-2. Accessed 1/5/2018.