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Fibrinolysis Comprehensive Panel
Test Summary
Clinical Use

  • Identify fibrinolytic disorders in patients with excessive bleeding or thrombosis

Clinical Background

Fibrinolysis involves breakdown of fibrinogen and fibrin clots into degradation products, while coagulation involves formation of fibrin clots from reactive fibrin monomers.1,2 In healthy individuals, the processes of fibrinolysis and coagulation are regulated by an interlinked system of substrates, enzymes, activators, and inhibitors (Figure).1 Disruption of the finely tuned processes of fibrinolysis and coagulation due to acquired or, in rare cases, hereditary causes may result in fibrinolytic abnormalities.1

Abnormal fibrinolysis is associated with excessive bleeding and thrombosis in critically ill patients and in those with certain chronic medical conditions. Excessive fibrinolysis can cause severe bleeding in patients with end-stage liver disease, as well as in those treated with fibrinolytic therapy, especially at sites of injury or surgery.3 At the other end of the spectrum, impaired fibrinolysis involving defective breakdown of fibrin clots is associated with type 2 diabetes, insulin resistance, sepsis, stroke, and the metabolic syndrome, in which it carries a 2-fold increased risk of coronary artery disease and stroke.1,4 Impaired fibrinolysis is also present in deep venous thrombosis (DVT) and pulmonary embolism (PE).5

Diagnosis of fibrinolytic abnormalities is critical for timely patient management and relies on clinical judgment along with laboratory analysis of intermediaries in the fibrinolysis/coagulation system. The Fibrinolysis Comprehensive Panel is most commonly used to detect fibrinolytic abnormalities in patients who are treated with fibrinolytic therapy or those with a history of bleeding. The panel also detects plasminogen deficiency, which has been associated with reduced fibrinolysis and increased thrombosis risk.1,2
Figure. Regulation of plasmin activation and the fibrinolysis/coagulation system.

Individuals Suitable for Testing

  • Individuals with unexplained excessive bleeding or thrombosis, especially at sites of injury or surgery

  • Individuals who have suffered a stroke or heart attack

  • Individuals who do not respond adequately to fibrinolytic therapy

Specimen Requirements

Four 1-mL aliquots of frozen plasma (sodium citrate, light blue-top tube); 0.8 mL minimum per aliquot

Morning fasting samples required. Avoid hemolysis, lipemia, fibrin clots, intense hyperbilirubinemia, and repeated freezing and thawing.

Method

Table 1. Methods Used to Measure Fibrinolysis Comprehensive Panel Markers
Marker Method
Alpha 2-antiplasmin Chromogenic assay
D-dimer Immunoturbidimetry
Euglobulin clot lysis time Clot dissolution
Fibrin monomer Hemagglutination
Fibrinogen degradation products Latex agglutination
Plasminogen activator inhibitor-1 (PAI-1) activity Chromogenic assay
Plasminogen activity Chromogenic assay
Tissue plasminogen activator (tPA) EIA

CPT codes*:  85415 x2, 85420, 85410, 85360, 85362 x2, 85379

Reference Ranges and Interpretive Information

Reference ranges and interpretive information for increased and decreased values of each marker are summarized in Table 2.

Table 2. Interpretive Information for Components of the Fibrinolysis Comprehensive Panel
Marker Reference Rangea Clinical Associations with Increased/
Positive Resultsa		 Clinical Associations with Decreased/ Negative Resultsa
Alpha 2-Antiplasmin 85%–156% normal activity Severe liver disease, amyloidosis; fibrinolytic therapy1,3
D-Dimer <0.5 μg/mL FEU DVT, PE, and DIC5,8,13
Euglobulin Clot Lysis Time >60 min Metabolic syndrome and CVD4 Severe liver disease, amyloidosis; fibrinolytic therapy1,3
Fibrin Monomer Negative DVT, PE, and DIC12,13
Fibrinogen Degradation Products <5 μg/mL DIC8
PAI-1 Activity 2.0–47.1 U/mL (M)

2.0–40.7 U/mL (F)

 Heart attack, stroke, DIC, type 2 diabetes;6-9 heart attack recurrence and death;10 resistance to thrombolytic therapy11 Severe liver disease, amyloidosis; fibrinolytic therapy1,3
Plasminogen Activity 65%–176% normal activity Acute promyelocytic leukemia3 Thrombosis1
tPA Antigenb 2.5–12.8 ng/mL Heart attack and stroke6,7

FEU, fibrinogen equivalent units; DVT, deep venous thrombosis; PE, pulmonary embolism; DIC, disseminated intravascular coagulation; CVD, cardiovascular disease; M, male; F, female; tPA, tissue plasminogen activator.
a Reference ranges are based on levels in normal controls and do not necessarily represent clinically relevant cutpoints. Clinical risks are associated with changes from reference levels that may differ from those listed.
b Refers to the amount of inactive tPA that is complexed with PAI-1. The higher the level of inactive tPA, the lower the fibrinolytic capacity.6
 

Normal D-dimer and negative fibrin monomer results may be used to rule out DVT and PE in patients with low clinical risk.13

Improper specimen collection and handling can cause inaccurate tPA antigen measurement and false-positive or false-negative fibrin monomer results.

This panel does not include the PAI-1 genotype test, which identifies patients homozygous for the PAI-1 4G allele. These patients tend to have elevated PAI-1 levels and are at greater risk of recurrent thrombosis and cardiovascular disease than individuals who are heterozygous for the 4G allele or homozygous for the 5G allele.14 The panel does not test for dysfibrinogenemia, which may be associated with bleeding, thrombosis, and pregnancy loss.15

References

  1. Cesarman-Maus G, Hajjar KA. Molecular mechanisms of fibrinolysis. Br J Haematol. 2005;129:307-321.

  2. Hajjar KA. The molecular basis of fibrinolysis. In: Nathan DG, Orkin SH, Ginsburg D, Look AT, eds. Hematology of Infancy and Childhood. Philadelphia, PA: W.B. Saunders Co.; 2003:1497-1514.

  3. Bovill EG. Systemic fibrinolysis. In: Goodnight S, Hathaway W, eds. Disorders of Hemostasis & Thrombosis: A Clinical Guide. 2nd ed. Columbus, OH: McGraw-Hill Professional; 2000:249-255.

  4. Anand SS, Yi Q, Gerstein H, et al. Relationship of metabolic syndrome and fibrinolytic dysfunction to cardiovascular disease. Circulation. 2003;108:420-425.

  5. Eichinger S, Minar E, Bialonczyk C, et al. D-dimer levels and risk of recurrent venous thromboembolism. JAMA. 2003;290:1071-1074.

  6. Juhan-Vague I, Pyke SDM, Alessi MC, et al; for the ECAT Study Group. Fibrinolysis factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. Circulation. 1996;94:2057-2063.

  7. Macko RF, Kittner SJ, Epstein A, et al. Elevated tissue plasminogen activator antigen and stroke risk: The Stroke Prevention In Young Women Study. Stroke. 1999;30:7-11.

  8. Levi M. Current understanding of disseminated intravascular coagulation. Br J Haematol. 2004;124:567-576.

  9. Festa A, D’Agostino R Jr., Tracy RP, et al. Plasminogen activator inhibitor-1 predict the development of type 2 diabetes. The Insulin Resistance Atherosclerosis Study. Diabetes. 2002;51:1131-1137.

  10. Sinkovic A, Pogacar V. Risk stratification in patients with unstable angina and/or non-ST-elevation myocardial infarction by Troponin T and plasminogen-activator-inhibitor-1 (PAI-1). Thromb Res. 2004;114:251-257.

  11. El Menyar AA, Altamimi OM, Gomaa MM, et al. The effect of high plasma levels of angiotensin-converting enzyme (ACE) and plasminogen activator inhibitor (PAI-1) on the reperfusion after thrombolytic therapy in patients presented with acute myocardial infarction. J Thromb Thrombolysis. 2006;21:235-240.

  12. Wada H, Wakita Y, Nakase T, et al. Increased plasma-soluble fibrin monomer levels in patients with disseminated intravascular coagulation. Am J Hematol. 1996;51:255-260.

  13. Elias A, Cazanave G, Nguyen F, et al. Comparison of the diagnostic performance of three soluble fibrin monomer tests and a D-dimer assay in patients with clinically suspected deep vein thrombosis of the lower limbs. Haematologica. 2004;89:499-501.

  14. Corsetti JP, Ryan D, Moss AJ, et al. Plasminogen activator inhibitor-1 polymorphism (4G/5G) predicts recurrence in nonhyperlipidemic postinfarction patients. Arterioscler Thromb Vasc Biol. 2008;28:548-554.

  15. Miesbach W, Galanakis D, Scharrer I. Treatment of patients with dysfibrinogenemia and a history of abortions during pregnancy. Blood Coag Fibrinolysis. 2009;20:366-370.
     

*The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed.
Content reviewed 09/2009
 
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