An observational study in Haemostasis Disorders, sponsored by Semmelweis University. Status unknown at 1 site in Hungary. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-02-07.
Sponsored by Semmelweis University · Observational
The purpose of the research is to compare the global and the portal haemostasis during liver transplantation by functional investigations using TEG® and ClotPro® tests. The study aims at revealing important coagulation-associated links affecting the outcome of the liver transplant surgery.
Donor data Liver donor data are investigated following the "Donor Query" used for donor reports of the Organ Coordination Office of the Hungarian National Blood Transfusion Service. (http://www.ovsz.hu/sites/ovsz.hu/files/szervadomanyozas_dokumentum/donacio/donorlekerdezo-2013-06-03.pdf) The donor is identified by the alarm ID and the Eurotransplant number (ETnr). Independently of this study, the "Donor Query" is completed for all donor reports and helps to asses donor suitability.
Recipient preoperative data In case of a liver alarm, age, body metrics, medical history, type and severity of hepatic disease, concomitant diseases, and admission laboratory test results of the recipient are recorded. Independently of this study, these data/procedures are recorded/performed for all liver transplant candidates.
Surgical data In addition to technical data of the surgery, data on intraoperative fluid balance, transfusion need, supportive therapy (vasopressor or inotropic therapy, renal replacement therapy), and number and indication of any reoperation are also recorded.
Intraoperative sampling times and investigations
During a liver transplantation, independently of this study, the following procedures are performed to monitor the patient's haemodynamics, homeostasis, and haemostasis:
During the study, for the analysis of haemostasis (TEG®, ClotPro®) and blood gases, 3.5 ml blood will be sampled per site and time from the external jugular vein catheter representing the systemic sample and from the portal vein representing the regional sample. Before performing the portal vein anastomosis, a small amount of blood is routinely flushed from the portal vein. Regional blood sampling is performed from this blood.
Systemic sampling is performed five times:
Regional sampling from the portal vein is performed once:
Simultaneously with haemostasis and blood gas analyses, the following investigations will be performed (as the part of the anaesthesia protocol):
Laboratory tests (quantitative and qualitative blood count, INR, aPTT, fibrinogen, AT, FV, FVII, FX, FXIII, C reactive protein (CRP), procalcitonin (PCT), electrolytes, creatinine, urea, bilirubin, liver enzymes, albumin, total protein, immunosuppressive drug levels) will be performed at the end of the surgery, at postoperative hours 12 and 24, on postoperative days 2, 3 and 7. As far as possible these tests will be carried out on day 30 and one year after the surgery as well.
Vasopressor and inotropic therapies will be analysed. The duration of assisted ventilation and the presence of pleural fluid or any sign of postoperative pneumonia will be evaluated. Urinary output as well as need for renal replacement therapy and the modality of that will also be investigated. Liver graft function will be monitored by means of laboratory parameters and graft perfusion with sonography. Initial poor function (IPF) and primary nonfunction (PNF) During the study, one-year graft and patient survival rates, the occurrence of small bile duct complications associated with arterial perfusion disorders, and the recurrence of underlying hepatic disease will be recorded. If a biopsy is taken within one year, histopathological results will also be evaluated.
Methodology and organisation of the study Informing patients on the study will occur during liver alarms by an anaesthesiologist. One copy each of the Patient Information Leaflet and the Informed Consent Form signed by the patient, the consenting physician and the principal investigator will be given to the patient. A copy of each of them will be filed in the medical records of the patient and the original one will be part of the research documentation.
During the study, tests for the investigation of parameters described in the protocol will be performed by the patients' physicians and other health care professionals involved in patient care.
Coagulation tests During the study, viscoelastic tests will be performed by TEG® and ClotPro® instruments.
Blood sampling for systemic TEG® and ClotPro® tests will be performed from the routinely catheterised external jugular vein while blood for regional tests will be taken from the portal vein of the recipient. After obtaining informed consent from the patient, 3.5 mL of blood samples will be collected in citrate tubes designated for the study at surgery phases described above. Investigations will be conducted by a TEG® 5000 thromboelastograph (Haemonetics Corp., Switzerland) and a ClotPro® (enicor GmbH, Germany) analyser. Results will subsequently be analysed by computed statistical tests. Simultaneously with viscoelastic tests, blood gas analyses will also be performed from the collected blood samples to obtain current pH, pCO2, and bicarbonate and calcium levels and their role in coagulation will be considered for the study. Furthermore, central body temperature will also be continuously monitored and recorded during the perioperative phase.
During TEG® and ClotPro® measurements in this study, the following parameters will be compared:
for TEG®, the following parameters will be considered in the study: R (reaction time): fluid phase of coagulation, time to formation of 2 mm clot; K (kinetics): time to formation of 20 mm clot; α: angle between 2 mm and 20 mm clot; MA (maximum amplitude): ultimate size of the clot; Ly30: percent rate of lysis at 30 minutes post MA. During the liver transplantation citrated kaolin test (CK-TEG) will be completed.
for ClotPro®, the following parameters will be considered in the study: CT (clotting time): indicates the fluid phase of coagulation (corresponds to R in TEG®); CFT (clot formation time): coagulation kinetics parameter, time between formation of 2 mm and 20 mm clot (corresponds to K in TEG®); α: angle (slope) of line between CT and CFT; A10 and A20 describe clot size (amplitude) at certain time points; MCF (maximum clot firmness): represents the ultimate size (maximum amplitude) of the clot (corresponds to MA in TEG®); clot lysis index at 30 (CLI30) describes the ratio between the maximum clot firmness and the amplitude 30 minutes after clotting time, LT (lysis time): characterises tPA effect.
During the liver transplantation EX-test, IN-test, FIB-test, TPA-test, RVV-test, and ECA-test tests will be completed.
Blood gas analyses Analyses are currently done by a GEM® PremierTM 3500 instrument. The blood gas analyser measures the following parameters: pH, pCO2, pO2, sodium, potassium, ionised calcium, blood glucose, lactate, bicarbonate, base excess, haemoglobin, haematocrit. Blood gas analyses are performed from the arterial and central vein samples. From the portal vein, blood sample is collected by the surgeon.
Laboratory parameters The following parameters will be measured at the laboratory by Sysmex CS 2000i, Sysmex XN-1000 (Sysmex Europe GmbH, Hungary) and Dimension® RxL Max® Integrated Chemistry System (Siemens Healthcare GmbH, Hungary)
Haemodynamic parameters Haemodynamic monitoring is performed for all patients undergoing liver transplantation in the perioperative period, independently from this study. Monitoring is done by a PiCCO instrument. During thermodilution measurements, cardiac output (CO), cardiac index (CI), intrathoracic blood volume index (ITBI), extravascular lung water index (EVLWI), stroke volume (SV), stroke volume variation (SVV), cardiac function index (CFI), maximum left ventricular contractility (dPmax), and mean arterial pressure (MAP) will be monitored.
CVP will be monitored via the catheterised subclavian vein. Time of each haemodynamic test is determined by the study protocol. Haemodynamic tests associated with this study do not differ from the current clinical practice and thus, pose no additional interventions over the standard care.
Oxygen delivery and consumption Parameters characterising oxygen delivery (oxygen delivery index; DO2I) and consumption (oxygen consumption index; VO2I) are calculated from arterial and central venous blood gas analysis results and from haemodynamic parameters.
Statistical methods Statistical analyses will be performed by Social Sciences software (SPSS; SPSS Inc, Chicago, Illinois, USA).
Continuous and discrete variables will be analysed by independent samples t tests (two categories) and one-way analyses of variance (one-way ANOVA; more categories), respectively. Two continuous variables will be compared by Spearman's rank correlation test. Discrete variables will be tested by Pearson's Chi squared test. Ordinary variables will be compared by Mann-Whitney U test or Kruskal-Wallis test. For multivariate analyses, logistic regression models will be generated.
Significance level will be set to 5% (p ≤ 0.05).
Semmelweis University is the lead sponsor of 136 studies on the registry; 54 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patients requiring liver transplantation for hepatic failure are to be enrolled at time of their liver transplantation.
Patients ≥18 years of age at the time of liver transplantation.
Exclusion criteria:
Systemic sampling is performed six times: * before the surgery (S1) * during the hepatectomy, 10 minutes before the anhepatic phase (S2) * in the anhepatic phase, before starting portal vein anastomosis: (S3) * in the neohepatic phase, 15 minutes after releasing portal vein clamping: (S4) * in the neohepatic phase, at the end of the surgery: (S5) Regional sampling from the portal vein representing afferent flow to the liver is performed once: • in the anhepatic phase, before starting portal vein anastomosis: (R) Simultaneously with haemostasis and blood gas analyses, the following investigations will be performed (the following tests are also routinely performed at the given time points, independently of this study): * haemodynamic measurements by PiCCO * arterial blood gas analysis from radial artery catheter * central venous blood gas analysis from subclavian vein catheter * blood temperature measurement in the femoral artery by PiCCO catheter * hourly urinary output
Also known as: Intreventional
Correlation between TEG® and ClotPro® parameters
If there is correlation between TEG® and ClotPro® parameters: 1. reaction time (R) in citrated kaolin TEG (CK-TEG) and clotting time (CT) in IN-test (ClotPro®) 2. kinetics (K) in CK-TEG and clot formation time (CFT) in IN-test 3. Alpha-angel in CK-TEG and IN-test 4. maximum amplitudo (MA) in CK-TEG and maximum clot firmness (MCF) in IN-test 5. percent rate of lysis (Ly30) in CK-TEG and clot lyzis index (CLI30) in IN-test
Time frame: 24 hours
Difference between systemic and the portal haemostasis
If there is a significant difference between the systemic and the portal haemostasis before graft reperfusion: 1. R, K, Alpha-angel, MA, MCF and Ly30 in CK-TEG from systemic and portal sample 2. CT, CFT, Alpha-angel, MCF, CLI30 in EX-test, IN-test, FIB-test, TPA-test, RVV-est, ECA-test from systemic and portal sample 3. Conventional laboratory tests: international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, antithrombin (AT), factor V (FV), factor VII (FVII), factor X (FX), factor XIII (FXIII) from systemic and portal sample 4. Blood gas analysis: pH, pCO2, pO2, sodium, potassium, ionised calcium, blood glucose, lactate, bicarbonate, base excess, haemoglobin, haematocrit from systemic and portal sample
Time frame: 24 hours
Correlation between the fetures of the intraoperative systemic and regional haemostasis and severity of the liver disease
1. Child-Turcotte-Pugh (CTP) score and CK-TEG (R, K, Alpha-angel, MA, MCF and Ly30) parameters from systemic and systemic samples 2. CTP score and ClotPro (CT, CFT, Alpha-angel, MCF, CLI30 in EX-test, IN-test, FIB-test, TPA-test, RVV-est, ECA-test) parameters from systemic and portal samples 3. Model for End-stage Liver Disease (MELD) score and CK-TEG (R, K, Alpha-angel, MA, MCF and Ly30) parameters from global and systemic samples 4. MELD score and ClotPro (CT, CFT, Alpha-angel, MCF, CLI30 in EX-test, IN-test, FIB-test, TPA-test, RVV-est, ECA-test) parameters from systemic and portal samples 5. MELD-Na score and CK-TEG (R, K, Alpha-angel, MA, MCF and Ly30) parameters from systemic and portal samples 6. MELD-Na score and ClotPro (CT, CFT, Alpha-angel, MCF, CLI30 in EX-test, IN-test, FIB-test, TPA-test, RVV-est, ECA-test) parameters from systemic and portal samples
Time frame: 24 hours
Correlation between local and systemic haemostasis and any subsequent coagulopathic or thrombotic complications
If there is a correlation between local and systemic haemostasis and any subsequent coagulopathic or thrombotic complications (reoperation for haemorrhage, portal vein or hepatic artery thrombosis). 1. Need for reoperation due to haemorrhage and CK-TEG (R, K, Alpha-angel, MA, MCF and Ly30) parameters from systemic and portal samples 2. Need for reoperation due to haemorrhage and ClotPro (CT, CFT, Alpha-angel, MCF, CLI30 in EX-test, IN-test, FIB-test, TPA-test, RVV-est, ECA-test) parameters from systemic and portal samples 3. Need for reoperation due to portal vein or hepatic artery thrombosis and CK-TEG (R, K, Alpha-angel, MA, MCF and Ly30) parameters from systemic and portal samples 4. Need for reoperation due to portal vein or hepatic artery thrombosis and ClotPro (CT, CFT, Alpha-angel, MCF, CLI30 in EX-test, IN-test, FIB-test, TPA-test, RVV-est, ECA-test) parameters from systemic and portal samples
Time frame: 24 hours
Plan to share: No
This study is status unknown, as verified in Feb 2020. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Semmelweis University