Test ID: PAI1
Plasminogen Activator Inhibitor Antigen, Plasma
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Identification of heredity elevation or deficiency of plasminogen activator inhibitor type 1
Determination of risk for veno-occlusive disease associated with bone marrow transplantation
Differential diagnosis of impaired fibrinolysis
Prognostic marker of occurrence or recurrence of thrombosis
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Enzyme-Linked Immunosorbent Assay (ELISA)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
See Coagulation Studies in Special Instructions.
Specimen Type: Platelet-poor plasma
Collection Container/Tube: Light-blue top (citrate)
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions:
1. Spin down, remove plasma, and spin plasma again.
2. Freeze specimen immediately at < or =-40 degrees C, if possible.
Additional Information:
1. Double-centrifuged specimen is critical for accurate results as platelet contamination may cause spurious results.
2. Each coagulation assay requested should have its own vial.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross reject |
| Lipemia | Mild OK; Gross reject |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Plasma Na Cit | Frozen | 14 days |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Plasminogen activator inhibitor type 1 (PAI-1) antigen is a single-chain glycoprotein (MW 50,000) produced by endothelial cells and hepatocytes and is also present in alpha granules of platelets. PAI-1 is a serine protein inhibitor that is secreted in response to inflammatory reactions. Platelet alpha granules contain large amounts of PAI-1, which is released during vascular injury and assists in fibrin clot stability. PAI-1 is synthesized in the active form but has marked functional instability and a functional half-life of about 2 hours in vivo. Circulating PAI-1 is bound to vitronectin, which protects the inhibitor from inactivation and may assist in targeting the inhibitor to sites of vascular injury. At least 4 different conformations of PAI-1 have been described: 1) the active form that reacts with plasminogen activator; 2) a latent form that is nonreactive; 3) a substrate form that can be cleaved by plasminogen activators but is noninhibitory; and 4) the inert form of PAI-1 generated by the cleavage of the reactive site.
PAI-1 is the main inhibitor of tissue-type plasminogen activator (tPA) and urokinase plasminogen activator (uPA) and, as such, plays an important role in the regulation of fibrinolysis. Elevated levels of PAI-1 result in deficient plasminogen activation and are associated with a predisposition to thrombosis, including veno-occlusive disease (VOD) after bone marrow transplantation (BMT).
Primary injury to the hepatic sinusoidal endothelium and hepatocytes induced by high-dose chemoradiotherapy is believed to be the key event in the pathogenesis of VOD. The clinical diagnosis of VOD is complex because the clinical signs and symptoms can occur as a result of other processes that can complicate the posttransplant period such as sepsis, graft-versus-host disease (GVHD), cyclosporine toxicity, other medications, hemolysis, or parenteral nutrition. Liver biopsy, although safer since the widespread introduction of transjugular procedures, remains hazardous in this thrombocytopenic population. A sensitive and specific assay would be invaluable in guiding management and avoiding potentially hazardous invasive diagnostic procedures. Along these lines several investigators have studied various markers of hypercoagulability for possible pathogenic and predictive relevance. Aside from serum bilirubin level, no laboratory marker has been standardized as a diagnostic marker of VOD and the severity of VOD remains retrospectively defined. Lee et al analyzed 115 patients after allogenic BMT in an attempt to identify diagnostic and severity markers of VOD. Of the 115 patients, 50 developed VOD.(1) Multiple logistic regression models were constructed that included recognized relevant clinical and hemostatic variables. Of the hemostatic variables, only PAI-1 antigen was identified as an independent marker for the occurrence of VOD. This confirmed findings of an earlier, smaller study, that PAI-1 is a powerful diagnostic marker of VOD during the early period post-BMT, and can distinguish VOD from other causes of hyperbilirubinemia post-BMT such as GVHD and drug toxicity. Furthermore, PAI-1 antigen and bilirubin were independent variables for predicting severe VOD.
Familial thrombosis has been associated with inherited elevation of plasma PAI-1 activity. Increased levels of PAI-1 have also been reported in a number of conditions including malignancy, liver disease, the postoperative period, septic shock, the second and third trimesters of pregnancy, obesity, and coronary heart disease.
Low plasma levels of the active form of PAI-1 have been associated with abnormal, clinically significant bleeding. Complete deficiency of PAI-1, either congenital or acquired, is associated with bleeding manifestations that include hemarthroses, hematomas, menorrhagia, easy bruising, and postoperative hemorrhage.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
3-72 ng/mL
Interpretation Provides information to assist in interpretation of the test results
Increased levels of plasminogen activator inhibitor type 1 (PAI-1) are associated with a predisposition to thrombosis.
Decreased or absent levels of detectable functional PAI-1 will result in a life-long bleeding diathesis.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The plasminogen activator inhibitor type 1 (PAI-1) level shows a diurnal variation with the highest levels occurring in the morning.
The PAI-1 level increases during pregnancy and decreases rapidly after delivery.
The extremely rare presence of antimouse antibodies in certain patients may lead to anomalous results.
Inappropriate specimen collection and processing may lead to platelet activation and release of platelet PAI-1. Consequently, care must be taken to remove all platelets and minimize platelet activation during specimen collection and processing.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Lee JH, Lee KH, Lee JH, et al: Plasminogen activator inhibitor-1 is an independent diagnostic marker as well as severity predictor of hepatic veno-occlusive disease after allogenic bone marrow transplantation in adults conditioned with busulphan and cyclophosphamide. Br J Haematol 2002;118:1087-1094
2. Stiko A, Hervio L, Loskutoff DJ: Plasminogen activator inhibitors. In Hemostasis and Thrombosis. Edited by RW Colman, J Hirsh, VJ Marder, et al. Philadelphia, Lippincott, 2001, pp 355-365
3. Vaughn DE, Declerck PJ: Regulation of fibrinolysis. In Thrombosis and Hemorrhage. Edited by J Loscalzo, AI Schager. Philadelphia, Lippincott, 2003, pp 389-396
4. Goodnight SH Jr, Hathaway WE: Fibrinolytic defects and thrombosis. In Disorders of Hemostasis and Thrombosis: A Clinical Guide. New York, McGraw-Hill Book Company, 2001, pp 389-396
5. Kruithof EK, Gudinchet A, Bachman F: Plasminogen activator inhibitor-1 and plasminogen activator inhibitor-2 in various disease states. Thromb Haemostasis 1988;59(1):7-12
6. Salat C, Holler E, Kolb HJ, et al: Plasminogen activator inhibitor-1 confirms the diagnosis of hepatic veno-occlusive disease in patients with hyperbilirubinemia after bone marrow transplantation. Blood 1997;89:2184-2188
7. Fay WP, Shapiro AD, Shih JL, et al: Brief report: complete deficiency of plasminogen-activator inhibitor Type 1 due to a frame-shift mutation. N Engl J Med 1992 Dec 10;327(24):1729-1733
Method Description Describes how the test is performed and provides a method-specific reference
Testing is performed on the Biomek FXP liquid handling system using the Diagnostica Stago, Inc. Asserachrom PAI-1 kit. The method used is an enzyme-linked immunosorbent assay (ELISA). Microtiter plate wells are coated with mouse monoclonal antihuman PAI-1 antibody, which captures the PAI-1 in the sample. Next, a second antibody (mouse monoclonal antihuman PAI-1) coupled with peroxidase binds to another antigenic site distant from the first antibody, forming the “sandwich.’’ The bound enzyme peroxidase is then visualized based on its ability to produce a color reaction when exposed to ortho-phenylenediamine and hydrogen peroxide. The reaction is stopped by the addition of a strong acid (1N HCl). The intensity of the color produced is directly proportional to the PAI-1
concentration in the plasma sample. (Declerck PJ, Alessi MC, Verstreken M, et al: Measurement of plasminogen activator inhibitor 1 in biologic fluids with a murine monoclonal antibody-based enzyme-linked immunosorbent assay. Blood 1988;71[1]:220-225)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Thursday; 12 p.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
83520
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 86083 | PAI-1 Ag, P | 22758-7 |
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