Table 5.

Assessment of coagulation status and management during neonatal ECMO

Anticoagulation
Administration of UFH: bolus of UFH 50 UI/kg at cannulation, followed by continuous infusion at 25 UI/kg/h
Coagulation monitoring and management
Parameter	Characteristics	Target	Intervention	Advantages	Disadvantages
AT	- Sample: citrated plasma - Endpoint: available AT	80–120%	Consider AT supplementation	- Possible optimization of UFH dose and effect	- Lack of evidence of improved clinical outcome following AT supplementation - Possible increased risk of bleeding and thrombosis
ACT	- Point of care test - Sample: whole blood - Endpoint: clot detection	180–220 s	Titrate UFH infusion, especially at ECMO start	- Small sample size (2–3 whole blood drops) - Low cost - Rapid and easy to perform - Suitable for transport	- Least related to UFH doses and UFH changes - Poor correlation with aPTT at lower UFH (risk of underestimation of heparin effect) - Influenced by hemodilution, thrombocytopenia, platelet dysfunction, hypothermia, age, coagulation factors deficiencies - Analyzer and reagent dependent
aPTT	- Clotting-based assay - Sample: citrated plasma - Endpoint: thrombus detection - Monitors intrinsic and common coagulation pathways (factors XII, XI, IX, X, V, II, fibrinogen)	Ratio 1.5–2.5 times baseline	Titrate UFH infusion Consider fresh-frozen plasma if aPTT is prolonged	- Low cost, widely used, readily available - Suitable for transport - Can detect underlying factor deficiencies (congenital or acquired), vitamin K deficiency, DIC in presence of UFH by using heparinase	- Lack of neonatal and pediatric ranges - Newborns have physiologically longer baseline levels compared to children and adults - Age-dependent effect of UFH on aPTT - Poor correlation with ACT and anti-Xa results in neonates - Mainly responsive to procoagulant drivers, does not reflect in vivo hemostasis - Influenced by UFH contamination of sample, hemodilution, coagulation factor deficiencies, and liver disease increased bilirubin, triglycerides, and plasma free Hb - Large blood sample size - Analyzer and reagent dependent - Risk of pre-analytic errors (i.e., suboptimal tube filling)
Anti-Xa	- Functional assay - Sample: citrated plasma - Endpoint: bound Factor Xa	0.3–0.7 IU/mL	Titrate UFH infusion	- Direct measurement of heparin effect on Factor Xa - Can monitor the effect of LMWH and oral Anti-Xa drugs - Calibration of aPTT reference ranges	- Anti-IIa effect not measured - Influenced by AT levels and assay type (exogenous AT, dextran sulfate additive), hyperbilirubinemia, triglycerides, and elevated plasma free Hb - High costs - Not available in all laboratories - Experienced staff needed
TEG	- Point of care test - Sample: whole blood - Endpoint: clot formation, strength, and breakdown • R time: time to factor IIa generation and fibrin formation; • Angle and K: fibrin mesh formation; • MA: platelet function and platelet fibrin interaction; • LY30: clot lysis 30 min after MA	R times in kaolin should be 2- to 3-fold longer than R times in heparinase (i.e., R times in kaolin 15–25 min)	Titrate UFH infusion and blood products Long R times in heparinase: consider fresh-frozen plasma administration Low ratio R kaolin/R heparinase: consider increase heparin High ratio R kaolin/R heparinase: consider decrease heparin Low MA values: check platelet count and fibrinogen levels and correct	- Small sample size - Rapid and easy to perform - Suitable for transport - Viscoelastic clotting tests with real-time global assessment of hemostasis (clot formation, strength, fibrinolysis) - Can monitor the role of fibrinogen and platelet - Can assess in vitro coagulation with UFH (kaolin) or without UFH (kaolin + heparinase), thus allowing to evaluate native hemostasis	- Influenced by the reagents and plasma free Hb - Lack of neonatal ranges of TEG parameters for anticoagulation during ECMO
Platelets	- Sample: EDTA blood - Endpoint: platelet count	> 80,000–100,000 if high risk of bleeding > 45,000 if low risk of bleeding	Consider administration of platelets (20 mL/kg)	- Low cost, widely used, readily available	- Platelet count does not reflect platelet function - Platelets may stick to the ECMO circuit components, contributing to either circuit deterioration and bleeding risk in patients
Fibrinogen	- Sample: citrated plasma - Endpoint: fibrinogen concentration	> 100–150 mg/dL	Consider administration of fibrinogen concentrate: - 50–70 mg/kg if fibrinogen < 50 mg/dL - 30 mg/kg if fibrinogen 50–100 mg/dL Consider fresh-frozen plasma	- Low cost, widely used, readily available - Role in detecting hypercoagulability and DIC, including the concurrent evaluation of platelet count and D-dimers	- Fibrinogen is usually depleted on ECMO and shows less sensitivity in detecting DIC
D-Dimers	- Sample: citrated plasma - Endpoint: available fibrin split products	< 300 μg/L	If D-dimer levels increase: - Check the circuit for clots - Consider changing the oxygenator	- Monitors fibrinolysis - Role in detecting hyperfibrinolysis and DIC together with fibrinogen status and platelet count trends	- Low specificity
PT	- Clotting-based assay - Sample: citrated plasma - Endpoint: thrombus detection - Monitors extrinsic coagulation pathway	Ratio < 1.5 times baseline	Consider fresh-frozen plasma if PT is prolonged	- Low cost, widely used, readily available - Suitable for transport - Can detect effects of vitamin K inhibitors and Anti-Xa agents	- Does not reflect the UFH effect - Age, analyzer, and reagent dependent - Large blood sample size

AT, antithrombin; UFH, unfractionated heparin; ACT, activated clotting time; aPTT, activated partial thromboplastin time; DIC, disseminated intravascular coagulation; EDTA, ethylenediaminetetraacetic acid; LMWH, low molecular weight heparin; TEG, thromboelastography; PT, prothrombin time

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