Plasminogen Activator Inhibitor 1 (PAI-1) Activity

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Category:

Turnaround Time: 3 - 5 days
CPT Code:

85415

Test Type: 0.5 mL Plasma, frozen
Stability Time:

Temperature

Period

Room temperature

Unstable

Refrigerated

Unstable

Frozen

11 days

Overview:

PAI-1 is a acute-phase reactant and can become transiently elevated by infection, inflammation, or trauma. PAI-1 levels increase during pregnancy.

Plasminogen activator inhibitor 1 (PAI-1) is a member of a family of proteins that inhibit plasminogen activators.6-8 PAI-1 is a single-chain glycoprotein with a molecular weight of 47 kilodaltons. During fibrinolysis, tissue plasminogen activator (tPA) converts the inactive protein plasminogen into plasmin. Plasmin, in turn, plays a critical role in fibrinolysis by degrading fibrin and also provides localized protease activity in a number of physiological functions, including ovulation, cell migration, and epithelial cell differentiation. PAI-1 is the primary inhibitor of tPA and other plasminogen activators in the blood. PAI-1 limits the production of plasmin and serves to keep fibrinolysis in check. Uncontrolled plasmin production can result in excessive degradation of fibrin and an increased risk of bleeding. PAI-1 levels are, in part, controlled on a genetic basis.6 Certain polymorphisms in the PAI-1 gene are associated with increased blood concentrations. Increased PAI-1 levels have been shown to be associated with a number of atherosclerotic risk factors.6,7 Insulin and proinsulin correlate with PAI-1 levels. Patients with insulin resistance syndrome and diabetes mellitus tend to have increased PAI-1 levels. Weight loss and treatment aimed at lowering triglyceride and/or cholesterol levels have also been shown to lower PAI-1 levels. PAI-1 has been shown to act as a prothrombic factor in both arterial and venous thromboembolic disorders.6,7 Increased levels of PAI-1 are associated with an increased incidence of acute coronary syndrome. PAI-1 levels are also increased in patients with chronic and acute coronary artery disease (CAD) and in patients who suffer restenosis after coronary angioplasty. It has also been shown that increased PAI-1 levels may reduce the effectiveness of antithrombolytic therapy.6,8 In fact, certain fibrinolytic agents, such as TNK-t-PA, are PAI-1-resistant and may be more effective in patients with increased PAI-1 levels. The method used for measuring PAI-1 activity in this test is an immunoassay that is specific for proteins that bind to tissue plasminogen activator (tPA) immobilized on a microtiter plate. The bound protein is then quantified using a monoclonal antibody that is specific for PAI-1. The assay is highly specific for protein recognized by the PAI-1 antibody that also has the ability to bind to tPA. Proteins with these characteristics are the predominant inhibitors of plasminogen activation in serum.6

1. Adcock DM, Kressin DC, Marlar RA. Effect of 3.2% vs 3.8% sodium citrate concentration on routine coagulation testing. Am J Clin Pathol. 1997 Jan; 107(1):105-110. PubMed 8980376

2. Reneke J, Etzell J, Leslie S, Ng VL, Gottfried EL. Prolonged prothrombin time and activated partial thromboplastin time due to underfilled specimen tubes with 109 mmol/L (3.2%) citrate anticoagulant. Am J Clin Pathol. 1998 Jun; 109(6):754-757. PubMed 9620035

3. National Committee for Clinical Laboratory Standardization. Collection, Transport, and Processing of Blood Specimens for Coagulation Testing and General Performance of Coagulation Assays; Approved Guideline. 5th ed. Villanova, Pa: NCCLS; 2008. Document H21-A5:28(5).

4. Gottfried EL, Adachi MM. Prothrombin time and activated partial thromboplastin time can be performed on the first tube. Am J Clin Pathol. 1997 Jun; 107(6):681-683. PubMed 9169665

5. McGlasson DL, More L, Best HA, Norris WL, Doe RH, Ray H. Drawing specimens for coagulation testing: Is a second tube necessary? Clin Lab Sci. 1999 May-Jun; 12(3):137-139. PubMed 10539100

6. Huber K, Christ G, Wojta J, Gulba D. Plasminogen activator inhibitor type-1 in cardiovascular disease. Status report 2001. Thromb Res. 2001 Sep 30, 103(Suppl 1):S7-S19. PubMed 11567664

7. Huber K. Plasminogen activator inhibitor type-1 (part one): Basic mechanisms, regulation, and role for thromboembolic disease. J Thromb Thrombolysis. 2001 May; 11(3):183-193 (review). PubMed 11577256

8. Huber K. Plasminogen activator inhibitor type-1 (part two): Role for failure of thrombolytic therapy. PAI-1 resistance as a potential benefit for new fibrinolytic agents. J Thromb Thrombolysis. 2001 May, 11(3):195-202. (review). PubMed 11577257

Collection Details:

Collection Instructions:

If the patient's hematocrit exceeds 55%, the volume of citrate in the collection tube must be adjusted. Refer to Sample Collection for Coagulation Testing for directions.

Blue-top (sodium citrate) tube.

Blood should be collected in a blue-top tube containing 3.2% buffered sodium citrate.1 Evacuated collection tubes must be filled to completion to ensure a proper blood to anticoagulant ratio.2,3 The sample should be mixed immediately by gentle inversion at least six times to ensure adequate mixing of the anticoagulant with the blood. A discard tube is not required prior to collection of coagulation samples, except when using a winged blood collection device (ie, "butterfly"), in which case a discard tube should be used.4,5 When noncitrate tubes are collected for other tests, collect sterile and nonadditive (red-top) tubes prior to citrate (blue-top) tubes. Any tube containing an alternate anticoagulant should be collected after the blue-top tube. Gel-barrier tubes and serum tubes with clot initiators should also be collected after the citrate tubes. Centrifuge and carefully remove the plasma using a plastic transfer pipette, being careful not to disturb the cells. Transfer the plasma into a LabCorp PP transpak frozen purple tube with screw cap (LabCorp N° 49482). Freeze immediately and maintain frozen until tested. To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit separate frozen specimens for each test requested.

Please print and use the Volume Guide for Coagulation Testing to ensure proper draw volume.

Freeze.