Redefining haemostasis: Role of rotational thromboelastometry in critical care settings

Table 1 Advantages of viscoelastic testing over traditional laboratory conventional coagulation testing

	Viscoelastic assays	Standard laboratory conventional coagulation test
Specimen type	Whole blood sample	Platelet-poor plasma
Result turnaround	Rapid results in minutes	Extended turnaround time
Testing site	Assessable and analysable at point of care	Conducted in a central laboratory
Clotting system assessment	Offers a comprehensive view of ex-vivo clotting	Indicates adequacy of thrombin generation, without insights beyond that
Validation for acute bleeding	Efficacy proven in multiple randomized controlled trials for improving patient safety and outcomes	Not validated for predicting bleeding risk or guiding transfusion

Table 2 Rotational thromboelastometry parameters and their clinical significance

ROTEM parameters	Clinical significance
Clot initiation: Clotting time	The time from the beginning of the test until a significant increase in resistance is observed, marking the onset of initial fibrin formation
Clot kinetics: Clot formation time	The duration from CT to reaching a clot firmness of 20 mm, reflecting fibrin polymerization and clot stabilization with the involvement of activated platelets and fibrin-stabilizing factor XIII
Clot kinetics: Alpha angle	The slope during the early phase of clot development, represented by the angle between the tangent line from the baseline to a 20 mm amplitude, indicates the rate of fibrin accumulation and cross-linking
Clot strength: Maximum clot firmness	The highest resistance recorded, due to enhanced clot stabilization by polymerized fibrin, activated platelets, and factor XIII, represents the maximum strength of the clot
Clot strength: Maximum lysis	The percentage decrease in MCF at specific intervals of 30 and 60 minutes, indicating clot stability and breakdown

CT: Clotting time; MCF: Maximum clot firmness; ROTEM: Rotational thromboelastometry.

Table 3 Rotational thromboelastometry delta/sigma and rotational thromboelastometry platelet assays

Assay	Activators and additives	Clinical significance
ROTEM delta/sigma
EXTEM	Calcium chloride + recombinant tissue factor + polybrene	Allow fast assessment of clot formation
		Explores the extrinsic coagulation pathway; VKAs; DOACs
		Increased values indicate need of PCC or FFP
		Not affected by aprotinin
		Sensitive to heparin
FIBTEM	Calcium chloride + recombinant tissue factor + polybrene + platelet inhibitor (cytochalasin D)	Depicts fibrin polymerization
		Assesses the contribution of fibrinogen to clot strength independent of platelets
		May also indicate XIII deficiency
		Used to calculate dose of fibrinogen concentrate or cryoprecipitate
APTEM	Calcium chloride + recombinant tissue factor + polybrene + aprotinin/tranexamic acid	Inhibition of premature lysis by addition of aprotinin/tranexamic acid
		In combination with EXTEM: (1) Rapid confirmation of fibrinolysis; (2) Verifying the effect of antifibrinolytic effect; and (3) Differential diagnosis of clot retraction and XIII deficiency
INTEM	Calcium chloride + ellagic acid	Assessment of clot formation and fibrin polymerization
		Explores the intrinsic coagulation pathway
		Increased values indicate need of FFP
HEPTEM	Calcium chloride + ellagic acid + heparinase	Testing in patients with very high heparin plasma concentrations
		In combination with INTEM
		To see UFH and protamine effects
NATEM	Calcium chloride	Expression of tissue factor on circulating cells, such as monocytes or cancerous cells
ECATEM	Calcium chloride + ecarin	Is sensitive for direct thrombin inhibitors (e.g., hirudin, argatroban, bivalirudin, dabigatran)
		Not sensitive to heparin
ROTEM platelet assays: These tests are used in patients treated with antiplatelet drugs or other medications that may affect platelet function, as well as in patients with suspected platelet dysfunction due to extracorporeal circulation, trauma, sepsis, or other reasons
ARATEM	Arachidonic acid	The platelets are activated with arachidonic acid to assess platelet function, particularly in patients treated with cyclooxygenase inhibitors such as acetylsalicylic acid
		Effects of CPB, trauma and sepsis on platelet function
ADPTEM	Adenosine di-phosphate	Platelets are activated using ADP to assess platelet function in patients treated with ADP receptor antagonists such as clopidogrel
		Effects of CPB, trauma and sepsis on platelet function
TRAPTEM	Thrombin receptor activating peptide-6	Platelets are activated using thrombin receptor activating peptide to evaluate platelet function in patients treated with PAR-1 receptor antagonists like vorapaxar or GP IIb/IIIa receptor antagonists such as abciximab
		Effects of CPB, trauma and sepsis on platelet function

ROTEM: Rotational thromboelastometry; DOACs: Direct oral anticoagulants; VKAs: Vitamin K antagonist; PCC: Prothrombin complex concentrate; FFP: Fresh frozen plasma; UFH: Unfractionated heparin; CPB: Cardiopulmonary bypass; ADP: Adenosine di-phosphate; PAR-1: Protease-activated receptor-1.

Table 4 Monitoring anticoagulant effects using rotational thromboelastometry

Anticoagulant type	ROTEM parameters	Details
Parenteral anticoagulants
UFH	INTEM-CT	Prolonged CT correlates to aPTT levels
	HEPTEM-CT	Normalized if prolonged CT was due to UFH/LMWH
	INTEM/HEPTEM CT-ratio	Correlation with anti-FXa activity > 0.1 IU/mL
LMWH	INTEM-CT	Low sensitivity, but prolonged only if anti-FXa activity is > 0.4 IU/mL
	NATEM/NAHEPTEM CT-ratio	Correlates with anti-FXa activity > 0.1 IU/mL
	TFTEM	Correlates anti-FXa activity
	PiCT	Correlates anti-FXa activity
Fondaparinux	INTEM-CT	Only prolonged in case of supratherapeutic plasma concentrations
Direct thrombin inhibitors	EXTEM-CT	Correlation with plasma concentrations of argatroban and bivalirudin
	ECATEM-CT	Prolongation specific for direct thrombin inhibitors
Oral anticoagulants
VKAs	EXTEM-CT	Correlates with PT-INR
	INTEM and HEPTEM-CT	INTEM and HEPTEM CT values typically remain normal
Dabigatran (correlates with plasma concentration)	ECATEM-CT	Prolonged, specific for direct thrombin inhibitors
	TFTEM/ECATEM CT-ratio < 2	Detects dabigatran effects
	EXTEM and FIBTEM-CT	Prolongation of CT in EXTEM and FIBTEM due to dabigatran
	INTEM and HEPTEM-CT	Prolonged clotting times
Rivaroxaban, edoxaban (correlates with plasma concentration)	TFTEM and EXTEM-CT	Prolongation of CT with rivaroxaban and edoxaban
	TFTEM/ECATEM CT-ratio > 2	Detects rivaroxaban and edoxaban
	INTEM and HEPTEM-CT	Less sensitive to rivaroxaban/edoxaban
	ECATEM-CT	Normal, specific for DTIs
Apixaban (correlates with plasma concentration)	EXTEM and INTEM-CT	Less sensitive to low concentrations of apixaban
	TFTEM/ECATEM CT-ratio > 2	Detects apixaban effects
	TFTEM CT	Sensitive to low concentrations of apixaban
	ECATEM-CT	Normal, specific for DTIs

CT: Clotting time; ROTEM: Rotational thromboelastometry; NATEM: Nonactivated thromboelastometry; TFTEM: Low tissue factor thromboelastometry; PiCT: Prothrombinase-induced clotting time; LMWH: Low-molecular-weight heparin; UFH: Unfractionated heparin; VKAs: Antivitamin K antagonists; ECATEM: Ecarin-activated assay; aPTT: Activated partial thromboplastin time; anti-FXa: Anti-factor X activated; INR: International normalized ratio; PT: Prothrombin time; DTI: Direct thrombin inhibitor.