Fibrinolytic Disorders

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

Laboratory Testing

  • Plasminogen activator inhibitor-1 (PAI-1)
    • Diurnal variation – higher values in the morning, lower values in the afternoon
    • PAI-1 deficiency identification is complex – values should be interpreted in conjunction with tPA values
      • Many laboratory assays are designed to identify elevated PAI-1 levels and cannot accurately quantify low values
      • Levels below the limit of quantification may be seen in both PAI-1-deficient patients and in individuals with normal levels
      • Specialized testing may be necessary to definitively diagnose severe PAI-1 deficiency
  • Plasminogen – activity testing
  • Alpha-2-antiplasmin – activity testing
  • tPA – antigen testing
  • Recurrent deep vein thrombosis in patient with negative workup for common defects – consider genotyping (SERPINE1)

Differential Diagnosis

Abnormalities in the fibrinolytic system may be associated with thrombosis or bleeding. Congenital fibrinolytic abnormalities are uncommon, but acquired abnormalities in this system are not unusual.

Pathophysiology

  • Formation of a fibrin clot occurs in response to vascular injury
  • Fibrinolytic system breaks down fibrin clot, converting fibrin to soluble degradation products
    • Components of the fibrinolytic system – plasminogen, plasminogen activators, plasminogen activator inhibitors, and alpha-2-antiplasmin
    • Fibrinolysis is precisely regulated by these activators, inhibitors, and cofactors

Components of Fibrinolytic System

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Plasminogen Activator Inhibitor-1, PAI-1 (SERPINE1) Genotyping 2004980
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than 4G/5G are not evaluated

Diagnostic errors can occur due to rare sequence variations

Plasminogen Activator Inhibitor 1, Activity 0098781
Method: Bioimmunoassay

Plasminogen Activity 0030190
Method: Chromogenic Assay

Alpha-2-Antiplasmin, Activity 0098727
Method: Chromogenic Assay

Tissue Plasminogen Activator, Antigen 0099187
Method: Enzyme-Linked Immunosorbent Assay

General References

Carpenter SL, Mathew P. Alpha2-antiplasmin and its deficiency: fibrinolysis out of balance. Haemophilia. 2008; 14(6): 1250-4. PubMed

Mehta R, Shapiro AD. Plasminogen activator inhibitor type 1 deficiency. Haemophilia. 2008; 14(6): 1255-60. PubMed

Mehta R, Shapiro AD. Plasminogen deficiency. Haemophilia. 2008; 14(6): 1261-8. PubMed

Rare Coagulation Disorders Resource Room - Rare Coagulation Disorders. Rare Coagulation Disorders Subcommittee of the National Hemophilia Foundation, and Indiana Hemophilia & Thrombosis Center. [Accessed: Feb 2017]

Schuster V, Hügle B, Tefs K. Plasminogen deficiency. J Thromb Haemost. 2007; 5(12): 2315-22. PubMed

Westrick RJ, Eitzman DT. Plasminogen activator inhibitor-1 in vascular thrombosis. Curr Drug Targets. 2007; 8(9): 966-1002. PubMed

Medical Reviewers

Last Update: April 2017