Article Figures & Data
Figures
- Fig 1.
Representation of stage of action of anticoagulants and their reversal agents on a schematic clotting cascade. This diagram is intended to summarise drug actions but does not reflect the complexity of haemostasis believed to occur physiologically, where cell surface molecules regulate initiation, amplification and propagation of thrombus.31 Please see the main text for details on specific drug and reversal agent mechanisms. PCC = prothrombin complex concentrate; LMWH = low-molecular-weight heparin; UFH = unfractionated heparin; → = promotes; = suppresses
Tables
Name Excretion Plasma half-life Warfarin Hepatic metabolism to inactive metabolites excreted in urine Effective half-life 40 h UFH Rapid endothelial cell internalisation (saturateable), slower renal clearance 45–90 min LMWH Predominantly renal 4 h Fondaparinux 70% renal 17–21 h Argatroban Hepatic 45 min Dabigatran 80% renal 13 h Apixaban 25% renal, 75% hepatic 12 h Edoxaban 35% renal, 65% hepatic 10–14 h Rivaroxaban 25% renal, 75% hepatic 5–9 h LMWH = low-molecular-weight heparin; UFH = unfractionated heparin
- Table 2.
Approximate time prior to surgery or invasive procedure for which anticoagulant drug should be stopped. National4 and local guidelines and product literature should be consulted for specific details
Drug Duration between stopping and invasive procedure or surgery Duration before stopping and invasive procedure or surgery in impaired renal function – creatinine clearance <30 Low bleeding risk procedure High bleeding risk procedure Low bleeding risk procedure High bleeding risk procedure Warfarin 5 days UFH 4 hours LMWH Prophylactic dose, 12 hours If used, discuss dose and timing with haematology Treatment dose, 24 hours Fondaparinux 24–42 hours If used, discuss dose and timing with haematology Argatroban 4 hours Dabigatran 24 hours 48 hours Cr Cl > 50 to <80: 24–48 hours Cr Cl > 50 to < 80: 48–72 hours Cr Cl > 30 to <50: 48–72 hours Cr Cl > 30 to <50: 72–96 hours Apixaban 24 hours 48 hours 48 hours 72 hours Edoxaban 24 hours 48 hours 48 hours 72 hours Rivaroxaban 24 hours 48 hours 48 hours 72 hours LMWH = low-molecular-weight heparin; UFH = unfractionated heparin
Drug Drug-specific reversal strategy Agents likely to be available in the future Vitamin K antagonists Vitamin K, four-factor PCC Unfractionated heparin Protamine sulphate Ciraparantag Low molecular weight heparin Protamine sulphate Andexanet alfa, Ciraparantag Fondaparinux Consider recombinant activated factor VII Andexanet alfa, Ciraparantag Dabigatran Idarucizumab Ciraparantag Factor Xa inhibitors Four-factor PCC Andexanet alfa, Ciraparantag PCC = prothrombin complex concentrate
- Table 4.
Effect of direct thrombin antagonists and Xa inhibitors on clotting tests, and drug-specific assays
Drug PT APTT TT Drug specific assay Normal Prolonged Normal Prolonged Normal prolonged Dabigatran Below or within therapeutic levels Supra-therapeutic levels Below or within therapeutic levels Within or above therapeutic levels Likely little or no drug present Cannot interpret Dilute thrombin time or ecarin clotting time Rivaroxaban Therapeutic levels unlikely but cannot be excluded Therapeutic or supratherapeutic levels Therapeutic or subtherapeutic levels Therapeutic or supratherapeutic levels Unaffected Rivaroxaban-specific anti Xa activity Apixaban Insensitive, cannot be assessed with these methods Unaffected Apixaban-specific anti Xa activity Edoxaban Therapeutic levels cannot be excluded Not useful Unaffected Edoxaban-specific anti Xa activity APTT = activated partial thromboplastin time; PT = prothrombin time; TT = thrombin time
