Hemostasis testing in patients with liver dysfunction: Advantages and caveats

Table 1 Randomized controlled trials assessing viscoelastic (tests) in patients with cirrhosis undergoing liver transplantation or invasive procedures and for the management of active bleeding

Ref.	VET	Population		n	Exclusion criteria	Intervention in the VET arm	Intervention in the SOC arm	Blood product	Bleeding
Liver transplantation
Wang et al[48], 2010	TEG	Adult patients with cirrhosis undergoing liver transplantation	28 patients (14 in each arm)		Unspecified	FFP titrated to maintain R time < 10 min; 6-8 pooled platelet units if MA < 55 mm; 5 pooled units of cryoprecipitate if alpha angle < 45 degrees	FFP titrated to maintain PT and APTT at less than one and a half times control; Platelets to maintain a platelet count ≥ 50 × 109/L; Cryoprecipitate to maintain fibrinogen > 1 g/L	FFP use: 12.8 units in the TEG arm vs 21.5 units in the SOC arm (P < 0.05); RBC: no difference; Platelets use: no difference; Cryoprecipitate use: no difference	Trend towards reduction in blood loss in the TEG arm (not statistically significant)
Bonnet et al[49], 2019	ROTEM	Adult patients with cirrhosis undergoing orthotopic liver transplantation	82 patients (41 in each arm)		Pregnancy; congenital coagulopathy; patients participating in another study	2 FFP units if EXTEM CT < 110 s; 1 platelet unit if EXTEM MCF < 40 mm or A10 < 35 mm and FIBTEM A10 or MCF > 8 mm; Fibrinogen 3 g if FIBTEM A10 < 8 mm	2 FFP units if PT < 40% at baseline or an hepatic phase or hemorrhage; PT < 30% at declamping or end of surgery and no hemorrhage; 1 platelet unit if platelet count < 50 × 109/L at baseline or an hepatic phase or hemorrhageor if platelet count < 30 × 109/L at declamping or end of surgery and no hemorrhage; Fibrinogen 3 g if fibrinogen ≤ 1 g/L	FFP use: 6 patients in the TEG arm vs 19 patients in the SOC arm (P = 0.002); RBC use: no difference; Platelets use: no difference; Cryoprecipitate use: 29 patients in the TEG arm vs 12 patients in the SOC arm (P < 0.001)	No difference in revision surgery or postoperative hemorrhage at 24 and 48 h
Invasive procedure
De Pietri et al[51],2016	TEG	Adult patients with cirrhosis undergoing invasive procedures with an INR > 1.8 and/or platelet count < 50 × 109/L		60 patients (30 in each arm)	Ongoing bleeding; current thrombotic events; antiplatelets or anticoagulants use; infection or sepsis; hemodialysis	FFP 10 mL/kg if R > 40 min; Platelets if MA < 30 mm	FFP10 mL/kg if INR > 1.8; Platelets if platelet count < 50 × 109/L	16.7% in the TEG arm vs 100% in the SOC arm (P < 0.0001)	1 post procedure bleeding after large volume paracentesis in the SOC arm
Vuyyuru et al[52],2019	TEG	Adult patients with cirrhosis undergoing invasive liver-related procedures with INR > 1.8 and/or < 50 × 109/L		58 patients(29 in each arm)	Cancer; hemophilia; DIC; antiplatelets use; pregnancy; renal failure; blood products in the previous 7 d	FFP if R > 14 min; 6-8 pooled platelet units; if MA < 30 mm	FFP if INR > 1.8; 6-8 pooled platelet units; if platelet count < 50 × 109/L	31% in the TEG arm vs 100% in the SOC arm (P < 0.001)	No bleeding in any group
Rocha et al[53],2020	ROTEM	Adult critically ill patients with cirrhosis undergoing CVC insertion		57 patients (19 per arm)	Acute liver failure; vonWillebrand’s disease; anticoagulants use; patients participating in another study	FFP10 mL/kg if CT EXTEM > 80 s; 1 apheresis platelets unit if A10 EXTEM < 40 mm and A10 FIBTEM ≥ 10 mm; 1 unit/kg of cryoprecipitate if A10 ESTEM < 40 mm and A10 EXTEM < 10 mm	SOC arm: FFP 10 mL/kg if INR > 1.5 or aPTT > 50 s 1 unit/kg of platelets if platelet count < 50 × 109/L; 1 unit/kg of cryoprecipitate if fibrinogen < 150 mg/dL; Restrictive arm: FFP 10 mL/kg if INR > 5; 1 unit/kg of platelets if platelet count < 25 × 109/L	Significantly lower in the restrictive arm (15.8% vs 68.4% in the ROTEM arm; P < 0.006 and vs 73.7%; P < 0.002) in the SOC arm. No difference between ROTEM and SOC arms	No major bleeding in any group
Active bleeding
Kumar et al[55],2020	TEG	Adult patients with advanced liver cirrhosis presenting with nonvariceal upper gastrointestinal bleeding with INR > 1.8 and/or platelet count < 50 × 109/L		96 patients (49 in the TEG arm, 47 in the SOC arm)	Variceal bleed; postvariceal ligation; ulcer bleed, previous or current thrombotic events; anticoagulant therapy at the time of enrollment or that had been discontinued less than 7 d before evaluation for the study; hemodialysis in the previous 7 d; pregnancy; significant cardiopulmonary disease	FFP 10 mL/kg if R > 10 min; 6-8 pooled platelet units if MA < 55 mm; 5 pooled units of cryoprecipitate if α-angle < 45 degrees	FFP 10 mL/kg if INR > 1.8; 6-8 pooled platelet units if plateletcount < 50 × 109/L 5 pooled units of cryoprecipitate if fibrinogen < 80 mg/dL	Patients transfused with all three blood components: 26.5% in TEG vs 87.2% SOC (P < 0.001)	No difference in failure to control bleeding or rebleeding on day 5. No difference in mortality on day 5 and on day 42
Rout et al[56],2020	TEG	Adult patients with cirrhosis presenting with acute variceal bleeding with INR > 1.8 and/or plateletcount < 50 × 109/L		60 patients (30 in each arm)	Malignancy; hemophilia; DIC; antiplatelets use; pregnancy; blood products in the previous 7 d; shock; sepsis; acute-on-chronic liver failure, renal failure, encephalopathy	FFP 5mL/kg if R > 15 min; 3 pooled units of platelets if MA < 30 mm	FFP if INR > 1.8; Platelets if platelet count < 50 × 109/L	13.3% TEG vs 100% SOC (P < 0.001)	No difference in control of bleeding or rebleeding on day 5 between the two groups.Rebleeding on day 42 less in TEG (10%) than SOC (36.7% ; P = 0.012)

A10: Amplitude at 10 min; ACLF: Acute-on-chronic liver failure; aPTT: activated partial thromboplastin time; CCT: Conventional coagulation test; CT: Clotting time; CVC: Central venous catheter; DIC: Disseminated intravascular coagulation; INR: International normalized ratio; FFP: Fresh frozen plasma; MA: Maximum amplitude; R: Reaction time; ROTEM: Rotational thromboelastometry; SOC: Standard of care; TEG: Thromboelastography; VET: Viscoelastic test.