Clinical utility of viscoelastic testing in chronic liver disease: A systematic review

Table 1 Rebalanced haemostasis in chronic liver disease

	Procoagulant factors	Anticoagulant factors
Primary haemostasis	Increased vWF	Thrombocytopenia
	Reduced ADAMTS13	+/- platelet dysfunction
Secondary haemostasis/coagulation	High FVIII	Reduced synthesis of FII, FV, FVII, FIX and FXI
	Reduced protein C, protein S and antithrombin
		Dysfibrinogenaemia
		Low fibrinogen (in end stage disease)
Fibrinolysis	Low plasminogen	Low antiplasmin
		Low TAFI
	High PAI-1	High tPA

ADAMTS13: A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; PAI-1: Plasminogen activator inhibitor-1; TAFI: Thrombin-activatable fibrinolysis inhibitor; tPA: Tissue plasminogen activator; vWF: von Willebrand factor.

Table 2 Comparison of thromboelastography and rotational thrombelastometry parameters

	Measurement	TEG	ROTEM
Period of initial fibrin formation	Time (min) to reach an amplitude of 2 mm	Reaction time (R)	Clotting time
Clot kinetics	Time (min) for clot amplitude to increase from 2 mm to 20 mm	Kinetics time (K)	Clot formation time
Clot kinetics	Angle of tangent line from clot initiation to the slope of the developing curve	Alpha angle (α)	Alpha angle (α)
Maximum clot strength	Peak amplitude (mm)	Maximum amplitude	Maximum clot firmness
Clot stability/fibrinolysis	Percent reduction in curve at 30 and 60 minutes	Lysis 30 (LY30) and lysis 60 (LY60)	Lysis index 30 (LI 30)

TEG: Thromboelastography; ROTEM: Rotational thrombelastometry.

Table 3 Randomised control trials assessing the use of thromboelastography in liver disease

Ref.	Year	No. of patients	Method of TEG	TEG thresholds for transfusion	SOC thresholds for transfusion	Outcomes: Blood product usage	Outcomes: Other
Wang et al[20]	2010	28	TEG 5000	FFP titrated to maintain R time < 10 min	FFP titrated to maintain PT and APTT at less than one and a half times control	Statistically significant reduction in FFP use in TEG group (12.8 units in TEG group vs 21.5 units in control group, P < 0.05)	Trend towards reduction in blood loss in the TEG arm (not statistically significant)
		14 TEG	Kaolin activated
		14 SOC
				SDAP when MA < 55 mm*
				5 pooled units of cryoprecipitate when alpha angle < 45 degrees**	Platelets to maintain a platelet count ≥ 50 × 109	No reduction in RBC, Platelet or cryoprecipitate use	No statistically significant difference in mortality at 3 yr
					Cryoprecipitate to maintain fibrinogen > 1 g/L
De Pietri et al[21]	2016	60	TEG 5000	FFP, 10 mL/kg*** when R time > 40 min1	FFP, 10 mL/kg*** when INR > 1.8	Statistically significant reduction in FFP use in TEG group. (Total amount of FFP transfused in those undergoing a low risk procedure: 4000 mL in TEG group vs 11050 mL in SOC group, P = 0.002) (Total amount of FFP transfused in those undergoing a high-risk procedure: 0 mL in TEG group vs 6500 mL in SOC group)	No statistically significant difference in periprocedural bleeding complications.
		30 TEG	Native blood (no activators)
		30 SOC
				SDAP when MA < 30 mm*	SDAP when platelets < 50 × 109*	Statistically significant reduction in platelets transfused. (6.7% required a platelet transfusion in the TEG arm vs 33.3% in the SOC arm, P = 0.021)	Periprocedural bleeding events were rare with only one patient experiencing post procedure bleeding.
Rout et al[22]	2019	60	MonoTEM-A®	FFP, 5 mL/kg*** when R time > 15 min	FFP, 5 mL/kg*** when INR > 1.8	Statistically significant reduction in FFP use. (13.3% receiving FFP in the TEG group vs 46.7% in the SOC group P = 0.010. 1345 ml LFFP transfused in the TEG group vs 4605 mL in the SOC)	No difference in initial control of bleeding
		30 TEG
			Native (no activators)
		30 SOC
							No difference in rates of re-bleeding at 5 d
				3 pooled units of platelets when MA < 30 mm*	3 pooled units of platelets when platelet count < 50 × 109*
							Statistically significant reduction in rebleeding at 42 d (10% in the TEG group vs 36.7% in SOC, P = 0.012)
						Statistically significant reduction in platelets transfused (10% in TEG group vs 70% SOC group P < 0.001. Total vol. of platelets transfused: 450 mL platelets in the TEG group vs 3450 mL in the SOC)
							No difference in mortality at 6 wk (13.3% in TEG group vs 26.7% in SOC, P = 0.176)
						No difference in RBC transfusion
Kumar et al[23]	2019	96	TEG 5000	FFP, 10 mL/kg*** when R time > 10 min	FFP, 10 mL/kg*** if INR > 1.8	Statistically significant reduction in FFP use (Total FFP transfused 440 mL in TEG vs 880 mL in SOC, P < 0.01)	Statistically significant reduction in transfusion related adverse events (30.6% in TEG group vs 74.5% in SOC P < 0.01)2
		49 TEG	Kaolin activated
		47 SOC
				SDAP when MA < 55 mm*	SDAP when platelets < 50 × 109*	Statistically significant reduction in platelets transfused (Average of 1 SDAP unit per patient in TEG group vs 2 SDAP units in SOC, P < 0.01)
				5 pooled units of cryoprecipitate when alpha angle < 45 degrees**	5 pooled units of cryoprecipitate if fibrinogen < 80 mg/dL**
							Statistically significant reduction in ICU length of stay (median of 2 d in TEG arm vs 3 d in SOC. P = 0.012)
						Statistically significant reduction in amount of cryoprecipitate used. (4 units in TEG group vs 16 in SOC group. P < 0.01)	No difference in failure to control bleeding at day 5 or rebleeding at day 42.
							No difference in 5-d and 42-d mortality
Vuyyuru et al[19]	2019	58	MonoTEM-A®	FFP 5 mL/kg when R time > 14 min***	FFP 5 mL/kg*** if INR ≥ 1.8	No statistically significant difference in the amount of FFP transfused (24.1% requiring FFP in the TEG group vs 27.6% in the SOC, P = 0.764)	No difference in post procedure bleeding complications (0% in both groups)
		29 TEG	Native (no activators)
		29SOC
					3 pooled units of platelets when platelet count < 50 × 109*
				3 pooled units of platelets when MA < 32 mm*
							No difference in pre and post procedure haemoglobin levels (TEG group: 11.3 ± 2.1 g/dL vs 11.2 ± 2.0 g/dL, P = 0.979; SOC group: 10.4 ± 2.1 g/dL vs 10.2 ± 2.0 g/dL, P = 0.205)
						Statistically significant reduction in platelets transfused (10.3% requiring platelet transfusion in the TEG group vs 75.9% in the SOC group, P < 0.001)

*In the above clinical trials, 1 SDAP unit corresponds to 6-8 pooled platelet units from whole blood donation. **When whole blood is used as the source for cryoprecipitate, 5 pooled units of is equivalent to 700 mg of fibrinogen. ***Ideal body weight used.

¹Natural whole blood used without added activators. Normal R time using this TEG method is 12-26 min.

²Higher than expected adverse reaction rate, including TRALI rates, not discussed in the paper. No information given about type of blood components used i.e., leucodepleted vs non-leucodepleted. APTT: Activated partial thromboplastin time; FFP: Fresh frozen plasma; INR: International normalised ratio; MA: Maximum amplitude; PT: Prothrombin time; R: Reaction time; RBC: Red blood cells; SDAP: Single donor apheresis platelets; SOC: Standard of care; TEG: Thromboelastography.