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

Abstract

<jats:sec><jats:title>Aims</jats:title><jats:p>Diagnosis 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Thirty consecutive adult patients undergoing OLT were included (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT03012633">NCT03012633</jats:ext-link>). Standard laboratory tests, ROTEM, GFC/LT, ECLT and fibrinolysis parameters were assayed at five sample times.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>GFC/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 &gt;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)).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>GFC/LT recognised hyperfibrinolysis during OLT with a significant agreement with the other tests of fibrinolysis.</jats:p></jats:sec><jats:sec><jats:title>Trial registration number</jats:title><jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT03012633">NCT03012633</jats:ext-link>.</jats:p></jats:sec>

Comparison of Two Thrombin Generation Methods, CAT and ST-Genesia, in Liver Transplant Patients

“…1B, the mean curves were calculated for all three assays' sampling time by sampling time: they illustrate that the samples withdrawn at T0 exhibit the highest TG, while the subsequent ones exhibit large alterations of the TG. However, T1 mean curve seems to be close to the T0 curve when assessed by the CAT method, which is in line with the absence of alteration between T0 and T1 with regard to the routine coagulation parameters (PT, activated partial thromboplastin time, anti-thrombin, factors V and II) 9 . ►Fig.…”

Hemostatic Effects of Tranexamic Acid in Cesarean Delivery: An Ancillary Study of the TRAAP2 Study

“…It has been shown that GFC/LT had very good diagnostic performances for detecting hyperfibrinolysis in trauma or liver transplantation contexts. 24,28 Previous studies have shown that the increase of fibrinolytic activity in the peripartum period was related to placenta delivery through a plasminogen inhibitors' plasmatic concentration decrease. 4,29,30 A t-PA increase has also been observed from the beginning of the labor, which could potentiate the supposed fibrinolytic activation at birth.…”

“…It has been shown that GFC/LT had very good diagnostic performances for detecting hyperfibrinolysis in trauma or liver transplantation contexts. 24 28…”

“…This method provides results in less than 1 hour and showed better diagnostic performance than viscoelastic tests in the setting of liver transplantation. 24 The TRAAP2 study, a multicentric randomized, double-blind placebo-controlled trial, was designed to assess the efficacy of prophylactic TXA in preventing PPH following cesarean delivery. 25 This trial showed that TXA treatment resulted in a significant decrease of the primary outcome-PPH defined as a calculated estimated blood loss >1,000 mL or needs for transfusion by day 2-but did not reduce hemorrhagerelated secondary clinical outcomes.…”

“…This method provides results in less than 1 hour and showed better diagnostic performance than viscoelastic tests in the setting of liver transplantation. 24…”