Fibrinolysis during liver transplantation: analysis by the Thrombodynamics method

An issue in orthotopic liver transplantation (OLT) is the diagnosis of hyperfibrinolysis. The Thrombodynamics-4D assay (TD4D) is a videomicroscopy system allowing the dynamic analysis of fibrin clot. Fibrinolysis is highlighted by a change in clot intensity. The aim of this observational study was to evaluate the TD4D as a tool to diagnose fibrinolysis during OLT. Thirty consecutive patients were included. We studied a subset of 41 samples from 13 patients who demonstrated hyperfibrinolysis during OLT by global fibrinolytic capacity studied by the Lysis Timer (GFC/LT) and/or euglobulin clot lysis time (ECLT) and/or EXTEM maximum lysis (EXTEM ML) on ROTEM. Three samples exhibited fibrinolysis. They exhibited significantly shorter ECLT, higher lysis on EXTEM graphs, shorter GFC/LT clot lysis time and higher t-PA activity values. After adding urokinase, 13 samples exhibited fibrinolysis. In conclusion, TD4D allows the dynamic analysis of fibrin clot formation and lysis. It only recognises the most severe forms of hyperfibrinolysis during OLT.

Laboratory monitoring of the haemostatic system changes during orthotopic liver transplantation

Introduction. In liver diseases, all components of the haemostatic system are changed and the degree of dysfunction is proportional to hepatocellular damage. During the liver transplantation, values of haemostatic parameters show substantial changes, while postoperatively there is a gradual normalisation of the haemostatic system function. Objective The aim was to monitor the changes of the haemostatic system intraoperatively and postoperatively, including the dynamics at which physiological values of parameters are reached after transplantation. Methods. There were 17 cadaveric transplantations performed at the Clinical Centre of Vojvodina in the period from June 2008 to February 2012. The following parameters were tested: platelets, activated partial thromboplastin, prothrombin and thrombin time, fibrinogen, euglobulin clot lysis time, D-dimer, antithrombin and heparinemia. The results were presented intraoperatively in phases of transplantation, and postoperatively from day 1 to day 7, ending with postoperative day 14. Results. During transplantation, the most pronounced disorders among those observed are: thrombocytopenia (96?66.1?109/L), prolonged activated partial thromboplastin (1.80?0.8 R), prothrombin (1.59?0.4 R) and thrombin time (2.03?1.7 R), hypofibrinogenemia (2.13?0.5 g/L), hyperfibrinolysis (29?12.0 min), increase of D-dimer (1393?1220.4 ng/mL) and decrease of antithrombin (61?18.0%). Further monitoring after transplantation from postoperative day 1 revealed a gradual normalisation in the values, reaching physiological values for all parameters on postoperative day 14, except for the sustained high value of D-dimer (2606?1055.1 ng/mL). Heparinemia was within the prophylactic range (0.26?0 IU/mL). Conclusion. Thorough monitoring of the haemostatic system parameters in liver transplantations is of great importance, as it enables the use of optimal substitution therapy during and after transplantation, as well as an adequate postoperative thromboprophylaxis. Our study has shown normalisation of investigated laboratory parameters within 7-14 days after transplantation.

Fibrinolytic parameters, lipid status and lipoprotein(a) in ischemic stroke patients

Introduction. Ischemic stroke is the third leading cause of mortality and morbidity in most countries in the world. Impaired fibrinolysis, as well as disordered lipid metabolism have been recognized as risk factors for this disease. Objective. To study some of fibrinolytic parameters, lipid status and lipoprotein(a) - Lp(a) in ischemic stroke patients in Serbia and to examine associations between Lp(a) and fibrinolytic parameters. Methods. Sixty ischemic stroke patients (case group, mean age 63.48?9.62 years) and 30 age and sex matched healthy controls (control group, mean age 60.2?7.96 years) were studied. Results. A significantly longer euglobulin clot lysis time (219.7?78,8 min. vs 183.5?58,22 min; p=0.005) and higher levels of plasminogen activator inhibitor-1 (PAI-1) (48.5?17.1 ng/ml vs 27.1?10.1 ng/ml; p=6.2?10-11), tissue-type plasminogen activator antigen (t-PA) (11.1?7.14 ng/ml vs 6,.0?3.66 ng/ml; p=5.2?10-5) and D-dimer (382.27?504.22ng/ml vs 116.12?88.81 ng/ml; p=0.0002) were found in cases compared to controls. There were no significant differences in fibrinogen levels (4.30?0.84 g/l vs 4.09?0.64 g/l; p=0.23) or plasminogen activity (92.67?11.37 % vs 96.87?9.48%; p=0.085). There was no significant difference in Lp(a) concentration between cases and controls (0.15?0.11 g/l vs 0.12?0.11 g/l; p=0.261). However, in the cases, but not in the controls, multivariate analysis of associations between fibrinolytic parameters and Lp(a) showed the highest correlation between t-PA and PAI-1, and the latent effect of Lp(a) on t-PA and PAI-1. Conclusions. Our results show that there are important differences in the characteristics of the fibrinolytic mechanism in ischemic stroke patients compared to healthy population. The major differences are prolonged euglobulin clot lysis time and elevated PAI-1 and t-PA antigen in ischemic stroke patients. In addition, Lp(a) appears to be involved in the inhibition of fibrinolysis in ischemic disease through a mechanism unrelated to its serum concentrations.

Plasma Fibrinogen Level Is an Important Determinant of Prolonged Euglobulin Clot Lysis Time in Hemodialysis Patients

The euglobulin clot lysis time (ECLT), a traditional measure of plasminogen activation, directly depends on plasma fibrinogen (FBG) level. This fact was neglected in studies concluding that prolonged ECLT in chronic hemodialysis (HD) patients pointed exclusively to impaired fibrinolysis. We studied the relations between ECLT and plasma FBG levels in HD patients in relation to certain hepatic and inflammatory markers. Median ECLT of 320 minutes (range, 150 to 620 minutes) and plasma FBG of 306 mg/dL (range, 171 to 553 mg/dL) were higher in 75 HD patients than in 60 healthy controls (Mann-Whitney p < 0.0001). There were positive associations between these parameters both in the patients (Spear-man p = 0.273, p = 0.018) and the controls (p= 0.672, p < 0.0001). The FBG-corrected ECLT (plasma FBG/ECLT) (in mg/min x dL]) in the patients (0.92 [range, 0.47 to 2.43]) was not different (p = 0.065) from that in the controls (1.08 [0.58 to 1.67]). In the patients, serum alanine aminotransferase inversely correlated with ECLT (p = -0.306, p = 0.008) and FBG (p = -0.310, p = 0.007). whereas serum C-reactive protein was associated positively with these variables (p = 0.383, p = 0.0007: p = 0.477. p <0.0001, respectively). The FBG-corrected ECLT was not related to either marker. In conclusion, increased plasma FBG level, a continuum between liver dysfunction and stimulation by chronic inflammation, is an important determinant of prolonged ECLT in HD patients. The FBG-corrected ECLT value suggests that baseline activation of fibrinolysis is normal in these patients, and that this simple index could be useful in its laboratory assessment.