Measuring Fibrinolysis

Abstract

Physiological fibrinolysis under normal conditions progresses slowly, in contrast to coagulation which is triggered rapidly to stop bleeding and defend against microbial invasion. Methods to detect fibrinolysis abnormalities are less simple and poorly standardized compared with common coagulation tests. Fibrinolysis can be accelerated by preparing euglobulin from plasma to reduce endogenous inhibitors, or by adding plasminogen activators to normal plasma. However, these manipulations complicate interpretation of results and diagnosis of a “fibrinolysis deficit.” Many observational studies on antigen levels of fibrinolysis inhibitors, plasminogen activator inhibitor 1 or thrombin-activatable fibrinolysis inhibitor, zymogen or active enzyme have been published. However, conclusions are mixed and there are clear problems with harmonization of results. Viscoelastic methods have the advantage of being rapid and are used as point-of-care tests. They also work with whole blood, allowing the contribution of platelets to be explored. However, there are no agreed protocols for applying viscoelastic methods in acute care for the diagnosis of hyperfibrinolysis or to direct therapy. The emergence of SARS-CoV-2 and the dangers of associated coagulopathy provide new challenges. A common finding in hospitalized patients is high levels of D-dimer fibrin breakdown products, indicative of ongoing fibrinolysis. Well-established problems with D-dimer testing standardization signal that we should be cautious in using results from such tests as prognostic indicators or to target therapies.

Serum Metabolic Profile in Patients With Long-Covid (PASC) Syndrome: Clinical Implications

“…An increase in DD correlates with mortality in severe COVID-19 infections (43), and although the clinical significance of elevated DD values has been recently reviewed and cautious interpretation is recommended (44), we postulate that the persistence of altered coagulation months after hospitalization should raise attention to the possible long term risks of thromboembolic disease in those patients, risks that have been discussed prevalently in acute settings along with the advantages and disadvantages of aggressive therapy (45). On the other hand, autopsies confirmed DD value in identifying the most serious COVID-19 dependent illnesses (46); the association between increased risk and high-dose steroid therapy has been observed (47).…”

Viscoelastometric Testing to Assess Hemostasis of COVID-19: A Systematic Review

“…Endogenous systemic fibrinolysis is usually weak because of low or even no circulating levels of free plasminogen activators, which are fully complexed to PAI-1 and thus inactive. Normal lysis of a whole blood clot is therefore a slow phenomenon [95], and its visualization on a VET trace recorded during one hour or two seems unlikely. Furthermore, as the zero value belongs to the manufacturer's reference range, speaking about a reduced or an absent fibrinolysis seems awkward if there is no control group for comparison.…”

“…Further studies are needed to evaluate the clinical value in this context of the in vitro study of thrombin generation, and particularly with the new automated ST Genesia device [118], as already mentioned elsewhere [128]. A potential issue could be the non-availability of such device and the high turn-around-time for a result There is also an unmet need regarding the exploration of fibrin polymerization and lysis [95] with good and convenient assays.…”

Fibrin clot properties in coronary artery disease: new determinants and prognostic markers

“…Standardization of the antigen assays as measurement of PAI-1 and t-PA is poor and it is not possible to directly compare absolute values across studies using different methods [34]. This limitation strongly compromises the aggregation of knowledge on the clinical significance of altered fibrinolysis in the onset and progression of disease.…”

“…However, these analyses only have limited sensitivity and capability of performing detailed analyses of fibrin clot properties. Bringing these limitations into mind, ROTEM/TEG assays can reveal severe hyperfibrinolysis, but protocols for application of these tests for investigation of hyperfibrinolysis in acute clinical care are still lacking [34].…”