Approach to thromboelastography-based transfusion in cirrhosis: An alternative perspective on coagulation disorders

Table 1 Three phases of coagulation in liver disease

Hemostasis stage	Hypocoagulable state	Hypercoagulable state
Primary hemostasis: Platelet activation and interaction with injured endothelium	Thrombocytopenia: (1) Decreased amount: Splenic sequestration, decreased thrombopoietin levels, bone marrow suppression, autoantibody destruction; and (2) Poor function: Uremia, changes to the vessel wall phospholipid composition, anemia (Hgb < 7 g/dL), decreased margination	Low levels of ADAMTS-13; Increased levels of vWF; Increased number of activated platelets
Secondary hemostasis: Fibrin clot formation	Low levels of factors II, V, VII, IX, X, and XI; Low levels of fibrinogen; Vitamin K deficiency (malabsorption in cholestatic disorders)	Elevated levels of factor VIII; Decreased levels of proteins C and S; Decreased levels of antithrombin, and heparin cofactor II
Fibrinolysis	Accelerated intravascular coagulation and fibrinolysis: (1) Low levels of factor XIII and thrombin-activated fibrinolysis inhibitor; (2) Elevated levels of tPA; (3) Decreased level of α2-antiplasmin; and (4) Dysfibrinogenemia	Low plasminogen levels; Dysfibrinogenemia; High plasminogen activator inhibitor

Hgb: Hemoglobin; tPA: Tissue plasminogen activator; vWF: von Willebrand factor.

Table 2 Thromboelastography components and their clinical implications

Nomenclature	Definition	Function	Significance	Most closely related CCT
Reaction time or R-time	Time (min) to reach an amplitude of 2 mm	Clot initiation	Informs about enzymatic reaction leading to thrombin and fibrin generation. Increased R-time, factor deficiency or reduced function, resulting in hypocoagulability; Shortened R-time, factor hypercoagulability	PT and aPTT
K-time	Time (min) from 2-20 mm amplitude	Clot kinetics	Depicts rate of clot development–fibrin polymerization, cross-linking, and platelet interaction. Long K-time, hypocoagulability; Short K-time, hypercoagulability	Fibrinogen level and platelet count
Angle or α	Slope between R and K	Clot kinetics	Also depicts the kinetics of clot development. Low-angle, hypocoagulability; High-angle, hypercoagulability
MA	Highest level of amplitude achieved by the clot	Clot strength	Provides assessment of overall clot strength	Platelet count and fibrinogen levels
Coagulation index	Composite indicator of coagulation profile		A linear combination of the above parameters serving as a global view of the patient’s hemostatic profile. Increased in hypercoagulable states; Decreased in hypocoagulable states
LY30	Degree of lysis (%) 30 min after MA is reached	Clot stability	Measure of fibrinolysis. Above normal LY30 suggests hyperfibrinolysis	No equivalent test

aPTT: Activated partial thromboplastin time; CCT: Conventional coagulation test; MA: Maximum amplitude; PT: Prothrombin time.

Table 3 Procedural bleeding risk in patients with cirrhosis

High-risk procedures	Intermediate-risk procedures	Lower-risk procedures
Intrabdominal/orthopedic/cardiac surgery	Percutaneous endoscopic gastrostomy	Paracentesis
Brain or spinal surgery	Percutaneous or transjugular liver biopsy	Thoracentesis
Intracranial catheter insertion	Transjugular intrahepatic portosystemic shunt	Central line placement
Endoscopic mucosal resection or endoscopic submucosal dissection	Endoscopy (e.g., percutaneous gastrostomy placement, cystogastrostomy, biliary sphincterotomy)	Endoscopy (e.g., diagnostic, variceal ligation, uncomplicated polypectomy)
Complicated polypectomy	Percutaneous biopsy of extra-hepatic organ or lesions	Cardiac catheterization
Natural orifice transluminal endoscopic surgery	Trans-arterial or percutaneous hepatocellular carcinoma therapies	Hepatic venous pressure gradient measurement
	Lumbar puncture

Table 4 Various types of thromboelastography assays

TEG channel	Activator	Function
Native TEG	None	Theoretically most sensitive to subtle coagulopathic changes and hyperfibrinolysis
Conventional TEG	Kaolin	Activates clotting cascade to expedite results
Rapid TEG	Tissue factor + kaolin	Activates clotting cascade to expedite results
Functional fibrinogen TEG	Glycoprotein IIb/IIIa inhibitor	Inhibits platelets to isolate the contribution of fibrinogen
Heparinase TEG	Heparinase	Inhibits heparin; the presence of heparin (endogenous or exogenous) is suggested when this channel shows improved clotting compared to other channels

TEG: Thromboelastography.

Table 5 Thresholds for coagulation parameters prior to high-risk procedures in patients with cirrhosis

Parameters	EASL 2022	ISTH 2021	AASLD 2021	AGA 2021
PT/INR	Against routine evaluation and correction	Against correction	Against correction	Against routine evaluation and correctiona
Platelet count	Against correctionb	Against correctionb	Against correction	Against routine evaluation and correctiona
Fibrinogen	Against routine correction	Against routine evaluation	Against correction	No specific recommendation
TEG	Against routine evaluationc	Do not use routinely	Do not use routinely	No specific recommendation

^aIn case of severe coagulopathy, prophylactic blood transfusions should be considered on case-to-case basis by evaluating potential benefits and risks in consultation with a hematologist.

^bIf the bleeding cannot be controlled by the local hemostasis method, administration of platelet concentrate or thrombopoietin receptor agonist can be considered if the platelet count is < 50000 × 10⁶/L.

^cMay provide a baseline coagulation status and guide in the case of bleeding events.

AASLD: American Association for the Study of Liver Diseases; AGA: American Gastroenterological Association; EASL: European Association for the Study of the Liver; INR: International normalized ratio; ISTH: International Society on Thrombosis and Hemostasis; PT: Prothrombin time; TEG: Thromboelastography.