Clinical Guidance

Because data on the phenotype associated with biallelic SERPINE1 pathogenic variants are limited, no genotype-phenotype correlations can be made at this time.

Source: GeneReviews — "Complete Plasminogen Activator Inhibitor 1 Deficiency"

Diagnostic Criteria

Suggestive Findings

Complete plasminogen activator inhibitor 1 (PAI-1) deficiency should be suspected in individuals with the following and .

Medical History

Bleeding disorder that typically presents as:

• Delayed bleeding following injury, trauma, or surgery

• In females, menorrhagia and abnormal bleeding with pregnancy

Absence of other known bleeding disorders including:

• von Willebrand disease

• Deficiencies of factor II, factor V, factor VII, factor VIII, factor IX, factor X, factor XI, factor XIII, or factor V VIII

• Alpha-2-antiplasmin deficiency

• Factor XIII deficiency

• Platelet function disorders (including Scott syndrome and Quebec platelet disorder)

Laboratory Findings

Normal. Common tests of coagulation including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin clo...

Source: GeneReviews — "Complete Plasminogen Activator Inhibitor 1 Deficiency"

Differential Diagnosis

lists genetic, mild-to-moderate bleeding disorders in the differential diagnosis of complete plasminogen activator inhibitor 1 (PAI-1) deficiency. With the exception of alpha-2-antiplasmin deficiency, bleeding in these disorders is typically associated with injury, surgery, or dental procedures. Table 2. Genes of Interest in the Differential Diagnosis of Complete Plasminogen Activator Inhibitor 1 Deficiency

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with complete plasminogen activator inhibitor 1 (PAI-1) deficiency, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Questions to elicit an individual's history of:

• Epistaxis

• Poor wound healing

• Bleeding in association with injury or trauma

• Bleeding with dental extractions

• Additional oral bleeding

• Postsurgical bleeding

• In females: heavy menstrual bleeding, postpartum bleeding, bleeding during pregnancy, preterm delivery, and bleeding in association with ovulation

• History of therapies tried in the past and the response to each specific therapy

Note: Response to antifibrinolytic therapy may support the diagnosis of complete PAI-1 deficiency .

• Evaluation by a hematologist with expertise in disorders of coagulation

• Consultation with a medical geneticist, certified genetic counselor, or certified advanced genetic nurse to inform affected individuals and their families about the nature, mode of inheritance, and implications of complete PAI-1 deficiency in order to facilitate medical and personal decision making

Treatment of Manifestations

Bleeding disorder. Management by a team of experts in the treatment of individuals with bleeding disorders is highly recommended. In the United States, such teams are often identified through the federally funded hemophilia treatment center network.

Source: GeneReviews — "Complete Plasminogen Activator Inhibitor 1 Deficiency"

Clinical Guidance

The following should be avoided:

• Medications that affect coagulation including aspirin, ibuprofen, and some herbal remedies

• High-risk activities such as contact sports

Source: GeneReviews — "Complete Plasminogen Activator Inhibitor 1 Deficiency"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Complete Plasminogen Activator Inhibitor 1 Deficiency"

Surveillance Guidelines

Bleeding disorder. Regular follow up with a team of experts in the treatment of individuals with bleeding disorders is recommended. Such teams are often identified through the federal hemophilia treatment center network in the US. For menstruating females:

• Regular monitoring of hemoglobin and/or hematocrit and iron studies including ferritin for possible iron deficiency and/or anemia

• Assessment of the effectiveness of therapeutic interventions such as antifibrinolytics or hormonal suppressive agents (oral contraceptives)

Cardiac fibrosis. Because of limited clinical experience with cardiac fibrosis in persons with complete PAI-1 deficiency , screening echocardiogram and EKG to assess cardiac function and cardiac MRI (to quantify cardiac fibrosis) can be considered at the time of diagnosis. The age of onset for cardiac fibrosis is not known in this population and follow-up screening should be considered [; ; Authors, personal observation].

Source: GeneReviews — "Complete Plasminogen Activator Inhibitor 1 Deficiency"