A look into hemostatic characteristics during pediatric liver transplantation using ROTEM®

A look into hemostatic characteristics during pediatric liver transplantation using the thromboelastometry (ROTEM^®) test

Cho J-K, Moon, J-Y, Song K-K, Kang E-J, Shin W-J, Hwang G-S. Liver Transplant. 2022;00:1­–12. DOI: 10.1002/lt.26463

This retrospective study used conventional coagulation tests and rotational thromboelastometry (ROTEM^®; ROTEM^® Delta, TEM International GmbH, Munich, Germany) to evaluate the coagulation profiles during liver transplantation (LT) in children, according to the cause of their liver disease. The study also assessed the reliability of ROTEM^® in children undergoing LT, compared to conventional coagulation tests.

Monitoring of coagulation status during LT helps to optimise blood transfusion and avoid over-correction of anticoagulation factors¹. It is even more crucial in children, who are more likely than adults to develop thrombotic complications^2,3 and for whom bleeding has more impact because of their small blood volumes⁴. However, very little is known about paediatric coagulation profiles. In addition, although the broad categories that warrant assessment for LT are similar for children and adults, the underlying causes and outcomes differ⁵. It is also unclear how, and to what extent, the underlying liver disease affects the coagulation system in children⁴.

ROTEM^® is already used in adult LT and major paediatric surgeries to help with managing transfusion requirements^1,6,7. ROTEM^® provides a global coagulation profile by measuring the viscoelasticity of clots using whole blood throughout the coagulation process. Conventional coagulation tests only measure the effect of coagulants and provide a coagulation profile for the clot initiation phase alone⁸; they also have a longer turnaround time¹.

Study design

In their retrospective study, Cho and colleagues evaluated a total of 106 patients (aged 3 months to 17 years) undergoing LT for acute liver failure (ALF; n = 20) and chronic liver disease (CLD; n = 86), the latter comprising cholestatic disease (n = 63), metabolic/genetic disease (n = 12) and cancer (n = 11).

Blood samples for ROTEM^® analysis and conventional tests were taken at 1 h after surgical incision (pre-anhepatic), 30 min during hepatectomy (anhepatic) and 30 min after graft perfusion (postreperfusion).

The study analysed 731 ROTEM^® measurements, including 301 of the intrinsic pathway (INTEM), 172 of the extrinsic clotting pathway (EXTEM) and 258 of platelet activity inhibition (as a measure of fibrinogen, FIBTEM) to obtain the following parameters:

• clotting time (CT): the time (s) until the initiation of clotting, as measured by a clot amplitude of 2 mm, for INTEM and EXTEM
• clot formation time (CFT): the time (s) from the initiation of clotting to a clot amplitude of 20 mm, for INTEM and EXTEM
• maximum clot firmness (MCF)

The ROTEM^® parameters were correlated with results from the conventional coagulation tests (i.e., activated partial thromboplastin time (aPTT), prothrombin time (PT), platelet count (PLT) and fibrinogen).

• aPTT was compared with both INTEM CT and CFT
• PT was compared with both EXTEM CT and CFT
• PLT was compared with MCF on EXTEM
• Fibrinogen concentration was compared with MCF on FIBTEM

Study outcome

Figure 1. Analysis of the area under the ROC curve for EXTEM and FIBTEM predicting thrombocytopenia and hypofibrinogenemia. AUC, area under the curve; EXTEM, extrinsic clotting cascade measurement; FIBTEM, fibrinogen function measurement; MCF, maximum clot firmness; ROC, receiver operating characteristics.

The results showed the following:

• Pre-anhepatic measurements with both conventional coagulation tests and ROTEM^® showed a more hypocoagulable state in children with ALF than with other types of liver disease
• The coagulation profile was deranged during LT, with a prolonged clotting time and reduced clot firmness. These changes were more profound in children with cholestatic liver disease.
• There was a good correlation between MCF on EXTEM and platelet count (r = 0.830, P< 0.001), and between MCF on FIBTEM and fibrinogen concentration (r = 0.739, P< 0.001)
• On the EXTEM, MCF with 30 mm predicted a platelet count <30,000/mm³ (area under the curve [AUC] 0.985), and MCF with 6 mm predicted a fibrinogen concentration <100 mg/dl on the FIBTEM (AUC 0.876 (Figure 1)
• There were only weak, but significant, correlations between aPTT and the intrinsic clotting pathway (INTEM CT and CFT) and with PT and the extrinsic clotting pathway (EXTEM CT and CFT)on ROTEM^®

In summary, the study showed that:

• Coagulation profiles in children vary during LT according to the cause of liver disease
• Clot firmness as detected by ROTEM^® could reliably discriminate thrombocytopenia and hypofibrinogenemia during paediatric LT
• ROTEM^® is a valuable point-of-care monitoring method for guiding transfusion therapy in paediatric LT
• These preliminary results support further evaluation in a large cohort

References

1. Hartmann M, Walde C, Dirkmann D, Saner FH. Safety of coagulation factor concentrates guided by ROTEM™-analyses in liver transplantation: results from 372 procedures. BMC Anesthesiol. 2019;19(1):97.
2. Hardikar W, Poddar U, Chamberlain J, Teo S, Bhat R, Jones B, et al. Evaluation of a post-operative thrombin inhibitor replacement protocol to reduce haemorrhagic and thrombotic complications after paediatric liver transplantation. Thromb Res. 2010;126(3):191-194.
3. Orlandini M, Feier FH, Jaeger B, Kieling C, Vieira SG, Zanotelli ML. Frequency of and factors associated with vascular complications after pediatric liver transplantation. J Pediatria. 2014;90(2):169-175.
4. Cho J-K, Moon Y-J, Song I-K, Kang E-J, Shin W-J, Hwang G-S. A look into hemostatic characteristics during pediatric liver transplantation using the thromboelastometry (ROTEM^®) test. Liver Transpl. 2022;00:1-12.
5. Squires RH, Ng V, Romero R, Ekong U, Hardikar W, Emre S, et al. Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline by the american association for the study of liver diseases, american society of transplantation and the north american society for pediatric gastroenterology, hepatology and nutrition. Hepatology. 2014;60(1):362-398.
6. Hartmann M, Craciun B, Paul A, Brenner T, Saner FH. Pre-Liver Transplant ROTEM™ Clot Lysis Index Is Associated with 30-Day Mortality, But Is Not a Measure for Fibrinolysis. J Clin Med. 2020;9(10):3298.
7. Drop JG, Erdem Ö, Wildschut ED, van Rosmalen J, de Maat MPM, Kuiper J-W, et al. Use of rotational thromboelastometry to predict hemostatic complications in pediatric patients undergoing extracorporeal membrane oxygenation: A retrospective cohort study. Res Pract Thromb Haemost. 2021;5(5):e12553.
8. Seeßle J, Löhr J, Kirchner M, Michaelis J, Merle U. Rotational thrombelastometry (ROTEM) improves hemostasis assessment compared to conventional coagulation test in ACLF and Non-ACLF patients. BMC Gastroenterology. 2020;20(1):271.