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
Hypercoagulation Panel
Plasminogen
Plasminogen Activator Inhibitor 1
Synonyms Alpha2-Antiplasmin; alpha2-Antiplasmin; Plasmin Inhibitor
Abstract Antiplasmin is a major inhibitor of plasmin. Hereditary antiplasmin deficiency is a rare familial bleeding disorder due to excessive fibrinolysis.
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; plasma may be stored on ice for up to 4 hours; otherwise store frozen.
Causes for Rejection Specimen received more than 4 hours after collection, tube not filled, clotted specimen
Turnaround Time Several days, because test is often sent out
Special Instructions Specimens for functional assays should not contain fibrinolysis inhibitors (eg, epsilon-aminocaproic acid, aprotinin) or heparin. Elevated alpha2-macroglobulin levels >200% may slightly interfere with functional assays.
Reference Interval Approximately 80% to 130% functional; approximately 48-80 mg/dL antigen. Antiplasmin levels (measured by antigen assay) are slightly lower during the first 5 days of life.1
Use Not a commonly performed clinical assay. May be considered in patients with strong evidence for a familial bleeding disorder and normal test results for more common bleeding disorders, such as von Willebrand disease.
Methodology
Functional (activity) assays: Excess plasmin is added to patient plasma. Antiplasmin in the patient plasma binds to and inhibits plasmin, forming a plasmin-antiplasmin complex. Residual plasmin then cleaves a chromogenic substrate, releasing a colored compound that can be detected spectrophotometrically. The amount of plasmin detected is inversely proportional to the concentration of antiplasmin in the patient specimen.
Antigen (immunologic) assay by radial immunodiffusion: Plasma is placed in a cylindrical well of an agarose gel. The agarose gel contains an antibody monospecific for antiplasmin. Antiplasmin in the specimen diffuses from the well into the gel where it forms a complex with the antibody, creating a precipitin ring. The size of the ring is proportional to the amount of antiplasmin in the plasma.
Additional Information Plasmin mediates fibrinolysis, and antiplasmin inhibits plasmin. Activated factor XIII cross-links antiplasmin to fibrin, and antiplasmin protects fibrin from plasmin-mediated fibrinolysis. Antiplasmin also binds to plasminogen and may inhibit plasminogen binding to fibrin. Antiplasmin is synthesized in the liver. Acquired causes of decreased antiplasmin include liver disease, thrombolytic therapy, and disseminated intravascular coagulation (DIC). Hereditary deficiencies of antiplasmin are either type I or type II. Type I deficiencies are quantitative, in which both functional and antigen levels are reduced. Type II deficiencies are qualitative, with decreased functional levels but normal or near normal antigen levels.
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.
References
Lijnen HR, Okada K, Matsuo O, et al, “alpha2-Antiplasmin Gene Deficiency in Mice Is Associated With Enhanced Fibrinolytic Potential Without Overt Bleeding,”Blood, 1999, 93(7):2274-81.
Yoshinaga H, Hirosawa S, Chung DH, et al, “A Novel Point Mutation of the Splicing Donor Site in the Intron 2 of the Plasmin Inhibitor Gene,”Thromb Haemost, 2000, 84(2):307-11.
