Hematological abnormalities in liver cirrhosis

Table 1 Comparison between the definitions of the values reported in thromboelastography and rotational thromboelastometry[34,120]

Section	Parameter	Definition and function
Clot initiation	ROTEM: CT	Measures from test start until fibrin begins to be formed (clot reaches a 2 mm diameter) and reflects time to fibrin formation. Low clotting factors and/or low fibrinogen level, vitamin K antagonists, heparin and DOAC use prolong this measurement. Recommended therapy: Fresh frozen plasma/prothrombin complex concentrate may be considered
	TEG: RT
Clot kinetics or fibrin polymerization	ROTEM: CFT	Reflects the speed at which fibrin is formed and how well it binds to platelets. It is the time it takes until the clot reaches 20 mm (arbitrary size). α angle is defined as the slope between section 1 and 2 and is a measure of the rapidity of fibrin polymerization. This parameter is dependent on sufficient fibrinogen, fibrin cross-linking and platelet number and function
	TEG: KT
	Both: Α angle
Clot strength or stiffness	ROTEM: MCF	It is the maximum clot diameter in millimeters and is a combined assessment of fibrinogen and platelet interactions. To differentiate their effects, the standard trace should be compared with the fibrinogen trace. For the clinician, this is the most useful parameter since it represents both primary and secondary hemostasis. Recommended therapy: Platelets (if normal fibrinogen assay), cryoprecipitate or fibrinogen concentrate (if low fibrinogen assay)
	TEG: MA
Clot breakdown or fibrinolysis	ROTEM: CL-30	As platelet retraction is a normal phenomenon, some clot strength diminution is expected. It is usually presented as a percentage reduction in the clot strength measure compared to maximal measurement at a given time (30 minutes after CT). Recommended therapy: Consider anti-fibrinolytic agent or reperfusion (if liver transplantation surgery)
	TEG: LY30

CT: Clotting time; RT: Reaction time; ROTEM: Rotational thromboelastometry; CFT: Clot formation time; TEG: Thromboelastography; KT: Kinetics time; MCF: Maximum clot formation; MA: Maximum amplitude; CL-30: Clot lysis at 30 minutes; LY30: Lysis at 30 minutes; PCC: Prothrombin complex concentrate; DOAC: Direct oral anticoagulant.

Table 2 Summary of blood products and/or drugs recommendations in bleeding in cirrhosis

Choice of agent	Recommendations			Guidelines/evidence
Platelet transfusion	Prophylaxis	Common gastrointestinal procedures1	AGA suggests against the routine use of blood products for bleeding prophylaxis	AGA[116,121]
		High risk procedures	Decisions about prophylactic blood transfusions should include discussions about potential benefits and risks in consultation with a hematologist. Threshold: > 50 × 109/L
	Acute bleeding	Platelet transfusions should not be administered based on platelet count targets because there is no evidence of benefit of such transfusions in AVH		AASLD[122]
		In patients with cirrhosis and active bleeding (out of the setting of AVH), thrombocytopenia (if platelet count < 50 × 109/L)		Clinical Gastroenterology and Hepatology[123], 2023
TPO-RA	Prophylaxis	Common gastrointestinal procedures1	AGA suggests against the routine use of TPO-RAs for bleeding prophylaxis	AGA[121]
		High risk procedures	Patients who place a high value on the uncertain reduction of procedural bleeding events and a low value on the increased risk for PVT can reasonably select a TPO-RA
	Acute bleeding	Not appropriate for acute setting		Clinical Gastroenterology and Hepatology[123], 2023
FFP	Prophylaxis	Common gastrointestinal procedures1	AGA suggests against the routine use of blood products for bleeding prophylaxis	AGA[121]
		High risk procedures	Decisions about prophylactic blood transfusions should include discussions about potential benefits and risks in consultation with a hematologist
	Acute bleeding	Fresh frozen plasma should not be administered based on INR because there is no evidence of benefit of such transfusions in AVH		AASLD[122]
		Restricted to hemorrhagic shock to compensate blood loss		Clinical Gastroenterology and Hepatology[123], 2023
Fibrinogen	Prophylaxis	No routine preprocedure correction		AASLD[89]
	Acute bleeding	The following transfusion thresholds for management of active bleeding or high-risk procedures may optimize clot formation in advanced liver disease: Fibrinogen > 120 mg/dL		AGA[116]
rFVIIa	Not recommended for bleeding episodes in patients with Child-Pugh A cirrhosis. Efficacy of rFVIIa was considered uncertain in bleeding episodes in patients with Child-Pugh B and C cirrhosis			European Consensus Critical Care[124], 2006
PCC	The role of PCC is not yet defined. Limited data based on retrospective studies			AGA[116]
Desmopressin	The agent lacks a sound evidence-based foundation but may be useful in patients with concomitant renal failure			AGA[116]
Antifibrinolytic agents	Anti-fibrinolytic therapy may be considered in patients with persistent bleeding from mucosal oozing or puncture wound bleeding consistent with impaired clot integrity			AGA[125]
	RCT shows tranexamic acid reduces failure to control bleeding and rebleeding in advanced cirrhosis with UGIB. However, further studies and robust evidence are needed to make a definitive recommendation			Hepatology[125], 2024

¹Paracentesis, thoracentesis, variceal banding.

FFP: Fresh frozen plasma; TPO-RA: Thrombopoietin receptor agonists; INR: International normalized ratio; AVH: Acute variceal hemorrhage; PCC: Prothrombin complex concentrates; rFVIIa: Recombinant activated factor VII; RCT: Randomized controlled trial; UGIB: Upper gastrointestinal bleeding; AGA: American Gastroenterological Association; AASLD: American Association for the Study of Liver Disease; PVT: Portal vein thrombosis.