Transfusion and coagulation management in liver transplantation

Table 1 Risks of transfusion

General risks
Transfusion related immunomodulation	Accumulation of immune mediators in stored blood
Transfusion associated circulatory overload	Acute left ventricular failure or congestive cardiac failure
Transfusion related acute lung injury	Capillary leak and neutrophil extravasation and activation caused by: Immune mediated: Donor antibodies react with recipient white blood cells, forming leukoagglutinate that become trapped in the lung Non-immune mediated: Endothelium suffers initial insult (e.g., sepsis, surgery or trauma), attracting neutrophils that are activated by biologically active compounds in stored blood
Haemolytic transfusion reactions	Immediate: Donor membrane antigens react with antibodies against these present in recipient plasma
	Delayed: Alloimmunised recipient with specific antibodies respond to re-exposure to antigen positive red blood cells
Acute non haemolytic transfusion reactions	Febrile: Donor leucocyte antigens react with recipient white cell antibodies
	Allergic: Soluble donor antigens react in an already sensitised recipient
Post-transfusion purpura	Previous sensitisation produces antibodies which attach donor platelet antigens and additionally destroy their own platelets
Transfusion associated graft vs host disease	Donor lymphocytes proliferate within immunocompromised recipient, attacking host cells as ‘‘foreign’’
Infection	Bacterial 1:2000-1:500000
	Viral: hepatitis B 1:450000; hepatitis C 1:32000000; HIV 1:5000000; human T-cell leukaemia virus 1:12500000

HIV: Human immunodeficiency virus; RBC: Red blood cells.

Table 2 Alterations in both anti- and pro- haemostatic dynamics in liver disease

Haemostasis	Anti-haemostatic	Pro-haemostatic
Primary haemostasis (platelet-vessel wall interaction)	Thrombocytopaenia	Elevated levels of Von Willebrand factor
	Platelet function defects	Decreased levels of ADAMTS-13
	Increased nitric oxide and prostacyclin	Platelet hyper reactivity
Secondary haemostasis (thrombin generation and inhibition)	Low levels of factors II, V, VII, IX, X, XI	Increased factor VIII
	Vitamin K deficiency	Decreased protein C, S, AT-III, alpha 2 macroglobulin, heparin co-factor II
Fibrinolysis	Low levels of alpha 2 anti-plasmin, factor XIII, thrombin activatable fibrinolysis inhibitor	Low levels of plasminogen
	Elevated tissue plasminogen activator	High levels of plasminogen activator inhibitor
	Dysfibrinogenaemia

Table 3 Coagulopathy during transplantation

Stage	Coagulation abnormalities increasing bleeding	Other risk factors for bleeding	TEG
Dissection	Thrombocytopaenia Platelet function defects Increased nitric oxide and prostacyclin Low levels of factors II, V, VII, IX, X, XI Vitamin K deficiency Low levels of alpha 2 anti-plasmin, factor XIII, thrombin activatable fibrinolysis inhibitor Elevated t-PA Dysfibrinogenaemia	Surgical technical difficulty Portal hypertension Oesophago-gastric venous distension secondary to compression and vascular clamping	Prolonged R time Decreased alpha-angle Reduced MA
Anhepatic	Reduced coagulation factor synthesis Reduced clearance of t-PA	Duration greater than 45 min	Increased lysis
Reperfusion	‘‘Heparin like effect’’ Platelet entrapment in sinusoids of donor liver Reduction of all coagulation factors Decreased PAI-1 Decreased antifibrinolytic factors Hyper-fibrinolysis	Acidosis Hypothermia	Virtually ‘‘flat’’ native trace with prolonged R time and significantly reduced MA Heparinase trace required Lysis
Post reperfusion	Accelerated t-PA release Thrombocytopaenia (balanced by increased activation)	Delayed graft function	MA reduced

TEG: Thromboelastography; MA: Maximum amplitude; t-PA: Tissue plasminogen activator; PAI-1: Plasminogen activator inhibitor.

Table 4 Parameters of viscoelastic tests - thromboelastography/rotational thromboelastometry

Parameter	TEG®	ROTEM®	Description
Clotting time	R	CT	Relates to concentration of soluble clotting factors in the plasma, the period of initial fibrin formation (time to reach 2 mm amplitude on the tracing)
Clot kinetics	K (K value) (min)	CFT	Measure the kinetics of clot formation
			Measures the speed to reach a specific level of clot strength (period for amplitude to increase from 2 to 20 mm)
	Alpha angle (angle in degrees) (°)	Alpha	Measures the rate of clot formation, reflects rate of fibrin build up and cross-linking (angle between a tangent to the tracing at 2 mm amplitude and the horizontal midline)
Clot strength	MA (mm)	MCF	Represents the ultimate strength of the clot (platelets and fibrin), maximum dynamic properties of fibrin and platelet bonding via GPIIb/IIIa receptors (greatest vertical width of tracing)
Clot stability	LY30	CLI	Relates to clot stability and lysis, measures the rate of amplitude reduction from MA at 30 min (in per cent)

TEG: Thromboelastography; ROTEM: Rotational thromboelastometry; R: Reaction time; CT: Clotting time; CFT: Clot formation time; MCF: Maximum clot firmness; CLI: Clot lysis index; MA: Maximum amplitude; MCF: Maximum clot firmness; LY30: Lysis at 30 min as a ratio of MA.