The euglobulin lysis time test: An ineffectual monitor of the therapeutic inhibition of fibrinolysis

Katz, J.; Lurie, A.; Becker, Débora da Luz; Metz, J.

doi:10.1136/jcp.23.6.529

Cited by 14 publications

(4 citation statements)

References 6 publications

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“…Once TXA has been administered, clot lysis is inhibited, and GFC/LT is always longer than 120 min. Oppositely, ECLT which necessitates a preanalytical step of inhibitors elimination (PAI-1, α2-antiplasmin, TAFI) also eliminates TXA and does not detect the inhibition of hyperfibrinolysis by the TXA treatment 24. In GFC/LT, the peak of the first derivative corresponds to the point where fibrinolysis is the fastest and is selected as the LT for the clot.…”

Section: Discussionmentioning

confidence: 99%

Lysis Timer: a new sensitive tool to diagnose hyperfibrinolysis in liver transplantation

et al. 2018

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AimsDiagnosis of hyperfibrinolysis in orthotopic liver transplantation (OLT) remains challenging. Euglobulin clot lysis time (ECLT) is not adapted to clinical situations. ROTEM is specific but seldom sensitive to hyperfibrinolysis. The Lysis Timer assesses ‘Global Fibrinolytic Capacity’ in citrated plasma (GFC/LT). GFC/LT associates reagents for in vitro triggering of the clot (thrombin and calcium) and its lysis (tissue-plasminogenactivator (t-PA)), turbidity signal acquisition by the Lysis Timer, and dedicated software converting the digital signal into an optical curve. A visual check of the curves was systematic to ascertain the lysis time values calculated by the software. The primary aim of this prospective observational study was to evaluate the ability of GFC/LT to recognise hyperfibrinolysis during OLT. The secondary aim was to compare its results with ROTEM maximum lysis (EXTEM ML) and with standard laboratory tests.MethodsThirty consecutive adult patients undergoing OLT were included (NCT03012633). Standard laboratory tests, ROTEM, GFC/LT, ECLT and fibrinolysis parameters were assayed at five sample times.ResultsGFC/LT was correlated with ECLT, plasmin activator inhibitor 1 antigen and activity and t-PA activity (r=0.490, 0.681, 0.643 and –0.359, respectively). Hyperfibrinolysis was defined as ECLT ≤60 min. Receiver operating characteristic curve analysis showed that GFC/LT with a threshold of 31 min detected hyperfibrinolysis with a sensitivity of 0.88 (95% CI 0.73 to 0.96), a specificity of 0.68 (95% CI 0.56 to 0.78) and an area under the curve (AUC) of 0.85 (95% CI 0.74 to 0.94). EXTEM ML >12% did not detect hyperfibrinolysis (sensitivity 0.38 (95% CI 0.24 to 0.55), specificity 0.95 (95% CI 0.86 to 0.99) and AUC 0.60 (95% CI 0.46 to 0.75)).ConclusionsGFC/LT recognised hyperfibrinolysis during OLT with a significant agreement with the other tests of fibrinolysis.Trial registration numberNCT03012633.

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Section: Discussionmentioning

confidence: 99%

Lysis Timer: a new sensitive tool to diagnose hyperfibrinolysis in liver transplantation

et al. 2018

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“…The ECLT in this group did not show a hypofibrinolytic state, but rather a normal state when compared to healthy volunteers. The difference between the ECLT and our ROTEM assay appears to be due to the fact that tranexamic acid does not precipitate in the ECLT test [ 31 ]. Reduced MCF is seen following dilutional effects during ECC by lowering fibrinogen levels and platelet numbers.…”

Section: Discussionmentioning

confidence: 99%

Validation of a modified thromboelastometry approach to detect changes in fibrinolytic activity

et al. 2016

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BackgroundThus far, validated whole blood assays used in in vitro fibrinolysis experiments using thromboelastometry (ROTEM) are lacking or have yet to be tested in humans.The objective was first, to establish a standardized modified ROTEM approach to detect both hypo- and hyperfibrinolysis. And second, to perform a technical and clinical validation of the assay.MethodsBlood was used of healthy volunteers, patients with sepsis, patients after cardiothoracic surgery, pregnant women, and cirrhotic liver disease patients. A whole blood tissue factor (TF) activated ROTEM assay with and without the addition of recombinant tissue plasminogen activator (rTPA) was developed. Plasma fibrinolysis determinants were measured in all volunteers and patients.ResultsThirty five pM TF and additions of 125 and 175 ng/ml rTPA resulted in full lysis within 60 min in healthy volunteers. Coefficients of variation were below 10 % without and below 20 % with rTPA addition. In sepsis the hypofibrinolytic ROTEM profiles with 175 ng/ml rTPA were in line with the plasma determinants (high PAI-1, high fibrinogen, low tPA activity, and high d-dimers). After cardiothoracic surgery, reduced fibrinogen and platelet levels accounted for the reduced maximum clot firmness. The hypofibrinolytic profile is attributed to tranexamic acid use and elevated PAI-1 levels. The lowest rTPA concentration in cirrhosis resulted in hyperfibrinolysis in only few of the patients. In pregnancy normal profiles were found.DiscussionOur high rTPA concentration demonstrates hypofibrinolytic profiles adequately in sepsis and after cardiothoracic surgery. Our low rTPA concentration of 125 ng/ml seems too high for demonstrating hyperfibrinolysis in cirrhotic liver disease.ConclusionsWe were able to present a validated whole blood ROTEM approach to fibrinolysis testing using added rTPA, which can be of added value next to classical plasma based fibrinolysis assays.

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“…104 Assessment of fibrinolysis in this setting has been historically through the euglobulin lysis assay, which fractionates whole blood eliminating cellular components and plasma proteins important for fibrinolysis inhibition. 105 This lack of fibrinolysis activation is found to occur in 30% of patients with a history of deep venous thrombosis (DVT). 106 This can be attributable to either elevated levels of PAI-1 or lack of release of tPA.…”

Section: Lack Of Fibrinolysis Activation—hypofibrinolysismentioning

confidence: 99%

Fibrinolysis Shutdown and Hypofibrinolysis Are Not Synonymous Terms: The Clinical Significance of Differentiating Low Fibrinolytic States

Moore

2022

Semin Thromb Hemost

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Low fibrinolytic activity has been associated with pathologic thrombosis and multiple-organ failure. Low fibrinolytic activity has two commonly associated terms, hypofibrinolysis and fibrinolysis shutdown. Hypofibrinolysis is a chronic state of lack of ability to generate an appropriate fibrinolytic response when anticipated. Fibrinolysis shutdown is the shutdown of fibrinolysis after systemic activation of the fibrinolytic system. There has been interchanging of these terms to describe critically ill patients in multiple settings. This is problematic in understanding the pathophysiology of disease processes related to these conditions. There is also a lack of research on the cellular mediators of these processes. The purpose of this article is to review the on and off mechanisms of fibrinolysis in the context of low fibrinolytic states to define the importance in differentiating hypofibrinolysis from fibrinolysis shutdown. In many clinical scenarios, the etiology of a low fibrinolytic state cannot be determined due to ambiguity if a preceding fibrinolytic activation event occurred. In this scenario, the term “low fibrinolytic activity” or “fibrinolysis resistance” is a more appropriate descriptor, rather than using assumptive of hypofibrinolysis and fibrinolysis shutdown, particularly in the acute setting of infection, injury, and surgery.

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The euglobulin lysis time test: An ineffectual monitor of the therapeutic inhibition of fibrinolysis

Abstract: SYNOPSIS

Cited by 14 publications

References 6 publications

Lysis Timer: a new sensitive tool to diagnose hyperfibrinolysis in liver transplantation

Lysis Timer: a new sensitive tool to diagnose hyperfibrinolysis in liver transplantation

Validation of a modified thromboelastometry approach to detect changes in fibrinolytic activity

Fibrinolysis Shutdown and Hypofibrinolysis Are Not Synonymous Terms: The Clinical Significance of Differentiating Low Fibrinolytic States

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