Plasminogen [CO003700]
Related Information
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.
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