Table 1 Anticoagulant Agents
From: Current and future strategies to monitor and manage coagulation in ECMO patients
Anticoagulant | Mechanism | Typical dosing | Monitoring | Half-life | Elimination | Reversal agent (Antidote) | Administration | Advantages | Disadvantages | Ref |
|---|---|---|---|---|---|---|---|---|---|---|
Heparin | Enhance the AT activity to inactivate thrombin; Inhibiting anti-FXa and AT | A bolus initial dose of 40–100 U/kg followed by a continuous infusion of 10–50 U/kg/hr, targeted to an aPTT or Anti-Xa level | Anti-factor Xa, ACT, aPTT, ROTEM/TEG, AT assay | 90 min | Renal and hepatic | Protamine | Intravenous (IV) | ● Well known mechanism of action ● Easy to monitor ● Easy titration ● Ease of reversibility with protamine ● Inexpensive | ● Non-linear dose–response relationship ● HIT induction ● Heparin resistance ● Depends on the level of AT | [61] |
Bivalirudin | Reversible direct thrombin inhibitor | It can be used with or without a bolus; A bolus initial dose of 0–0.75 mg/kg and a maintenance dose of between 0.025 and 0.5 mg/kg/h | Plasma level of drug, ECT, aPTT, diluted thrombin time (dTT), ACT | 25 min | Renal (20%) and hepatic (80%) | None | IV | ● No HIT induction ● Short half-life ● Independent of AT levels | ● Bivalirudin resistance requiring dose escalation ● Interferes with fibrin production, platelet aggregation, and factor XII activation ● Prolonged half-life and drug accumulation in renal failure | [62] |
Argatroban | Reversible direct thrombin inhibitor | Typically, no bolus loading is required (However, some centres use 100–200 \(\mathrm{\mu g}/\mathrm{kg}\)) A maintenance infusion of rate between 0.1 and 2 \(\mathrm{\mu g}/\mathrm{kg}/\mathrm{min}\) | aPTT, diluted thrombin time, ACT, ECT, ROTEM/TEG | 39 to 51 min; depending on hepatic function | Hepatic | None | IV | ● No HIT induction ● Fewer transfusions than heparin ● Independent of AT levels | ● Increased dose required to maintain therapeutic range over time ● Less familiar to most clinicians ● Long onset of action ● Interferes with fibrin production, platelet aggregation and factor XII activation ● Prolongs the aPTT, ACT, PT/INR results | [63] |
Danaparoid | Factor Xa inhibitor | 200–300 U/hr | Anti‐factor Xa assay | 19‐25 h | Renal | None | IV and subcutaneous | ● Recommended for HIT situation ● Some anti-thrombin activities | ● Has been unavailable for several years due to manufacturing issues | [64] |
Fondaparinux | Factor Xa inhibitor | 2.5–10 mg/day | Anti‐factor Xa assay | 17–21 h | Renal | None | IV and subcutaneous | ● High level of activity ● Recommended for HIT situation ● Its activity is 20 times greater than the danaparoid | ● Does not inhibit thrombin ● Major bleeding in HIT patients ● Restricted usage in renal dysfunction situation ● Not for use while actively undergoing ECMO | [65] |
Nafamostat mesylate | Inhibits many procoagulant factors including thrombin, factors XIIa, Xa, and antifibrinolytic and anti-platelet action | 0.26–0.93 mg/kg/hr | ACT, aPTT | 8 min | Renal | None | IV | ● Short half-life | ● Limited published data on its safety and efficacy | [66] |
Warfarin | Inhibits vitamin K-dependent clotting factors (II, VII, IX, X) | Initial dose of 10 mg and maintenance dosage of 1–2 mg per day | INR | 20–60 h | Mainly hepatic and minor enzymatic | Vitamin K, prothrombin complex concentrates (PCC) and fresh frozen plasma (FFP) | IV or orally | ● Long-term anticoagulation after ECMO ● Easy administration ● Reversibility | ● Not for use while actively undergoing ECMO ● Not a good choice for acute HIT situation ● High drug interactions and dose adjustment required | [67] |
Dabigatran | Reversible direct thrombin inhibitor | 75–150 mg per day | ACT, aPTT, ECT and thrombin time (TT) | 12–17 h, up to 34 h in renal failure | Renal | Idarucizumab (Praxbind) | Oral | ● Does not require frequent laboratory monitoring due to its low drug–drug and drug–food interactions ● Reversibility | ● Induces dyspepsia ● High cost ● Limited published data on its safety and efficacy ● Limited application in ECMO due to long onset of action | [68] |
Rivaroxaban | Factor Xa inhibitor | 15–20 mg per day | Prothrombin time, Anti‐factor Xa assay | 5–9 h in healthy young people and 11 to 13 h in elderly people | Both renal and hepatic | Andexanet alfa | Oral | ● Does not require frequent laboratory monitoring ● Reversibility | ● Limited information about using DOACs in ECMO patients due to long onset of action and prolonged half-life | [69] |