From: Elizabeth M. Van Cott, M.D., and Michael Laposata, M.D., Ph.D., “Coagulation.” In: Jacobs DS et al, ed. The Laboratory Test Handbook, 5th Edition. Lexi-Comp, Cleveland, 2001; 327-358.
Related Information
Disseminated Intravascular Coagulation Screen
Hypercoagulation Panel
Plasminogen Activator Inhibitor 1
Applies to Acute Phase Reactant; Conjunctivitis, Ligneous; Fibrinogenolysis; Fibrinolysis; Tissue Plasminogen Activator; tPA; uPA; Urokinase-Type Plasminogen Activator
Abstract Plasminogen is the precursor of plasmin, which lyses fibrin clots. Hereditary plasminogen deficiency is rare, and it may predispose to venous thrombosis.
Specimen Plasma
Container Blue top (sodium citrate) tube
Collection Routine venipuncture. If multiple tests are being drawn, draw blue top tubes after any red top tubes but before any lavender top (EDTA), green top (heparin), or gray top (oxalate/fluoride) tubes. Immediately invert tube gently at least 4 times to mix. Tubes must be appropriately filled. Deliver tubes immediately to the laboratory.
Storage Instructions Separate plasma from cells as soon as possible. Store plasma on ice for up to 4 hours, or store frozen.
Causes for Rejection Specimen received more than 4 hours after collection, tubes not filled, clotted specimens
Turnaround Time 1 day or longer, depending on how often testing is batched
Reference Interval Functional results are reported as a percent of the amount expected in normal plasma. By definition, the mean value in normal plasma is 100%. The reference range is approximately 75% to 130%. Antigen results may be reported in mg/dL, with a reference range of approximately 6-14 mg/dL. Plasminogen levels can increase during pregnancy. Newborn levels are about 60% of adult values. Newborn levels increase to near adult values by age 6 months.1
Use May be considered in patients with familial venous thrombosis and no evidence for more common hypercoagulable states. Occasionally, if monitoring of thrombolytic therapy is desired, plasminogen levels are followed. Plasminogen decreases during thrombolytic therapy. Consider testing plasminogen in patients with ligneous conjunctivitis, a condition that is associated with severe plasminogen deficiency.
Limitations Plasminogen may become elevated during pregnancy and during acute phase reactions. Antigen assays will not detect qualitative (dysfunctional) deficiencies.
Methodology
Functional (activity) assays: Chromogenic assays for plasminogen are available. Streptokinase is added to patient plasma, which binds to plasminogen. The streptokinase-plasminogen complex has plasmin-like activity2 which cleaves a chromogenic substrate, releasing a colored-compound. The amount of color detected spectrophotometrically is proportional to the amount of plasminogen in the sample.
Antigen (immunologic) assays: Radial immunodiffusion methods are commercially available.
Additional Information Plasminogen is converted into plasmin by tissue plasminogen activator (tPA) or urokinase-type plasminogen activator (uPA). Plasmin degrades fibrin clots (fibrinolysis) as well as intact fibrinogen (fibrinogenolysis). Plasmin also inactivates factors Va and VIIIa. Plasminogen can be decreased during thrombolytic therapy, liver disease, disseminated intravascular coagulation (DIC), and rarely, with a hereditary plasminogen deficiency. The incidence of plasminogen deficiency is 0.29% to 0.73% in healthy individuals, up to 1.4% to 2.2% among patients with venous thrombosis, and 1.4% among patients with arterial thrombosis.3,4,5 In one study, 2.5% of a general population with plasminogen deficiency had a history of thrombosis.5 Hereditary deficiencies of plasminogen could result in decreased fibrinolysis. However, the association with thrombosis is somewhat uncertain. In some studies, plasminogen-deficient relatives of affected individuals have similar rates of thrombosis as nondeficient relatives,4 whereas in other studies they do have a higher rate of thrombosis.6 Severe hereditary plasminogen deficiency is associated with ligneous conjunctivitis, a rare chronic pseudomembranous conjunctivitis characterized histologically by massive deposits of fibrin in the affected tissues.7,8 Apparently, the fibrin depositions result from decreased or absent clearance of fibrin by plasminogen.
Footnotes
1. Andrew M, Paes B, Milner R, et al, “Development of the Human Coagulation System in the Full-Term Infant,”Blood, 1987, 70(1):165-72.
2. Reddy KN and Markus G, “Mechanism of Activation of Human Plasminogen by Streptokinase: Presence of Active Center in Streptokinase-Plasminogen Complex,”J Biol Chem, 1972, 247(6):1683-91.
3. Heijboer H, Brandjes DP, Buller HR, et al, “Deficiencies of Coagulation-Inhibiting and Fibrinolytic Proteins in Outpatients With Deep-Vein Thrombosis,”N Engl J Med, 1990, 323(22):1512-6.
4. Biasiutti FD, Sulzer I, and Stucki B, “Is Plasminogen Deficiency a Thrombotic Risk Factor? A Study on 23 Thrombophilic Patients and Their Family Members,”Thromb Haemost, 1998, 80:167-70.
5. Tait RC, Walker ID, Conkie JA, et al, “Isolated Familial Plasminogen Deficiency May Not Be a Risk Factor for Thrombosis,”Thromb Haemost, 1996, 76(6):1004-8.
6. Girolami A, Sartori MT, Saggiorato G, et al, “Symptomatic Versus Asymptomatic Patients in Congenital Hypoplasminogenemia: A Statistical Analysis,”Haematologia (Budap), 1994, 26(2):59-65.
7. Schuster V, Seidenspinner S, Zeitler P, et al, “Compound-Heterozygous Mutations in the Plasminogen Gene Predispose to the Development of Ligneous Conjunctivitis,”Blood, 1999, 93(10):3457-66.
8. De Cock R, Ficker LA, Dart JG, et al, “Topical Heparin in the Treatment of Ligneous Conjunctivitis,”Ophthalmology, 1995, 102(11):1654-9.
References
Schuster V, Zeitler P, Seregard S, et al, “Homozygous and Compound-Heterozygous Type I Plasminogen Deficiency Is a Common Cause of Ligneous Conjunctivitis,”Thromb Haemost, 2001, 85(6):1004-10.
