Plasminogen Activity

Plasminogen is a glycoprotein with molecular weight of 92 kilodaltons that is produced by the liver.^6-8 The plasma half-life of plasminogen is about two days.⁶ Plasminogen is converted to the proteolytic enzyme plasmin by cleavage of a single peptide bond.⁶ Plasmin degrades fibrin clots and intact fibrinogen (ie, fibrinogenolysis).⁷ Plasmin also inhibits coagulation by inactivating factors Va and VIIIa.⁷

Plasminogen deficiency is not considered a risk factor for thrombosis.⁶ Hereditary deficiencies in plasminogen activity are rare and include type 1 deficiency, characterized by decreased plasminogen protein levels, and type II deficiency, characterized by normal levels of dysfunctional plasminogen production. Plasminogen deficiency is usually transmitted as an autosomal recessive defect.⁶ Homozygous plasminogen deficiency can result in ligneous conjunctivitis, a condition in which large amounts of fibrin are deposited in the conjunctiva.⁷ Fibrin deposits can occur in other tissues as well, leading to a variety of disorders.

There are two physiologic activators of plasminogen, tissue plasminogen activator (TPA), and urinary-type plasminogen activator (UPA). Thrombin generated during coagulation stimulates the release of TPA from the endothelial cells. TPA release also occurs as the result of exercise or stress.⁶ Treatment with desmopressin (DDAVP) also causes the release of TPA. TPA forms a complex with fibrin, which, in turn, converts plasminogen to plasmin. Kallikrein, a protein component of the contact system, stimulates the release of UPA from the kidneys;⁶ however, in healthy individuals, the majority of this released UPA is bound to the endothelial tissue urokinase plasminogen activator receptor (uPAR). Streptokinase (SK) produced by β-hemolytic streptococci can also activate plasminogen. All three of these activators have been used therapeutically to dissolve pathologic clots. Plasminogen levels drop in patients undergoing thrombolytic therapy with TPA, UPA, or SK and measurement of plasminogen activity can be used to monitor the therapeutic efficacy of this treatment.⁶

Plasminogen activator inhibitors (PAI) inhibit plasminogen activation in vivo.⁶ Measurement of PAI-1 levels has clinical application in the assessment of thrombophilia.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. Adcock DM, Bethel MA, Macy PA. Coagulation Handbook. Aurora, Colo: Esoterix−Colorado Coagulation; 2006.

7. Van Cott EM, Laposata M. Coagulation. In: Jacobs DS, DeMott WR, Oxley DK eds. Laboratory Test Handbook With Key Word Index. Hudson, Ohio: Lexi-Comp; 2001:327-358.

8. Bachmann F. Plasminogen-plasmin enzyme systems. In: Colman RW, Hirsh J, Marder VJ, et al, eds. Hemostasis and Thrombosis, Basic Principles and Clinical Practice. 4th ed. Philadelphia, Pa: Lippincott Williams and Wilkins; 2000: 275-320. Adcock DM, Ramanathan R. The fluid and tissue phases of the plasminogen system.Lab Med. 2004 Jun; 35(6):364-367.