Anticoagulants

  • Xarelto (rivaroxaban)
    • factor Xa inhibitor
    • measure small elevation in INR/PTT; anti-factor Xa level
    • stop 24hrs prior to surgery
    • possible partial reversal with aPCC, may need 12hr re-dosing.
  • Eliquis (apixaban)
    • factor Xa inhibitor
    • measure small elevation in INR/PTT; anti-factor Xa level
    • stop 48hrs prior to surgery
    • possible partial reversal with aPCC, may need 12hr re-dosing.
  • Savaysa (edoxaban)
    • factor Xa inhibitor
    • measure small elevation in INR/PTT
    • stop 24hrs prior to surgery
    • possible partial reversal with aPCC, may need 12hr re-dosing.
  • Pradaxa (dabigatran)
    • direct thrombin inhibitor
    • measure elevated INR/PTT
    • stop 1-2d prior to surgery if CrCl>50ml/min or stop 3-5d prior to surgery if CrCl<50ml/min; may need longer times for major surgery
    • partial reversal with PCC and dialysis
    • full reversal with idarucizumab 2.5g x2 15min apart; immediate onset; lasts 24hrs.
  • Argatroban
    • direct thrombin inhibitor
    • measure elevated INR/PTT
    • stop 4hrs before surgery
    • no reversal
  • bivalirudin
    • direct thrombin inhibitor
    • elevated PTT
    • stop 2hrs before surgery
    • reverse partially with dialysis and rFVIIa
  • fondiaparinux
    • factor Xa inhibitor
    • measure possibly elevated anti-factor Xa level
    • stop 4d before surgery
    • possible partial reversal with aPCC, may need 12hr re-dosing; rFVIIa
  • Deltaparin / Lovenox LMWH
    • indirect thrombin inhibitor
    • measure anti-factor Xa level
    • stop 1d prior to surgery
    • partial reversal with protamine
  • Plavix (clopidogrel)
    • blocks ADP receptor on platelets
    • measure platelet function assay, ROTEM, TEG with platelet mapping
    • stop 7d before surgery
    • partial reversal options include: 10U platelets, DDAVP ug/kg IV re-dosed PRN 8-12hrs, possibly TXA
  • Pletal (cilostazol)
    • phosphodiesterase inhibitor (increases cAMP), reversible platelet aggregation inhibitor
    • no measure
    • unsure, may stop 7d before surgery
    • no reversal
  • Effient (prasugel)
    • blocks ADP receptor on platelets
    • stop 7d before surgery
    • partial reversal options include: 10U platelets, DDAVP ug/kg IV re-dosed PRN 8-12hrs, possibly TXA
  • Brillanta (ticagrelor)
    • reversibly blocks ADP receptor
    • stop 5d before surgery
    • partial reversal options include: 10U platelets, DDAVP ug/kg IV re-dosed PRN 8-12hrs, possibly TXA
  • Ticlid (ticlopidine)
    • blocks ADP receptor on platelets
    • stop 10-14d before surgery
    • partial reversal options include: 10U platelets, DDAVP ug/kg IV re-dosed PRN 8-12hrs, possibly TXA
  • Persantine (dipyridamole)
    • increases cAMP
    • stop 48hrs before surgery
  • Aggrenox (asa/dipyridamole)
    • antiplatelet COX inhibitor and increases cAMP
    • stop 7d before surgery
    • partial reversal options: platelets
  • ReoPro (abciximab)
    • inhibits GP IIb/IIIa
    • stop 36-48hrs before surgery
    • partial reversal options include: 10U platelets, DDAVP ug/kg IV re-dosed PRN 8-12hrs, TXA
  • Integrilin (eptifibatide)
    • inhibits GP IIb/IIIa
    • stop 4-6hrs before surgery
    • partial reversal with DDAVP; wait to give platelets until medication is cleared

References:
individual drug web sites

Antithrombotic Agents Commonly Encountered in the Surgical Setting
AgentMedical indicationMechanism of actionHalf-life, hStrategy for reversalLast dose before operation
Unfractionated heparinArterial embolism or VTE prevention and treatment; treatment of atrial fibrillation with embolization; bridging therapyAntithrombin III mediated selective inhibition of Factor Xa1–2Protamine sulfateIntravenous: 2–6 h; subcutaneous: 12–24 h
Low-molecular-weight heparins; Enoxaparin (Lovenox, Sanofi-Aventis US LLC)DVT treatment and preventionAntithrombin III mediated selective inhibition of Factor Xa2Protamine sulfate (only partially effective)24 h
Warfarin (Bristol-Myers Squibb Co)Stroke prevention in atrial fibrillation or cardiac valve replacement;

DVT/PE treatment and prevention; recurrent MI prevention
Vitamin K antagonist20–60Vitamin K;

4-factor PCC8;

FFP
5 d
Dabigatran etexilate (Pradaxa, Boehringer Ingelheim Pharmaceuticals, Inc)Stroke prevention in atrial fibrillation;

DVT/PE treatment and prevention
Direct thrombin inhibitor8–15Idarucizumab9; hemodialysis; 4-factor PCC1024–48 h
Rivaroxaban (Xarelto, Janssen Pharmaceuticals, Inc)Stroke prevention in atrial fibrillation;

DVT/PE treatment;

DVT/PE prevention
Direct factor Xa inhibitor5–134-factor PCC1124–48 h
Apixaban (Eliquis, Bristol-Myers Squibb Co)Stroke prevention in atrial fibrillationDirect factor Xa inhibitor124-factor PCC1224–48 h
Edoxaban (Savaysa, Daiichi Sankyo, Inc)Stroke prevention in atrial fibrillation; DVT/PE treatment and preventionDirect factor Xa inhibitor10–144-factor PCC1324–48 h
AspirinPrevention of MI, TIA, and CVACyclooxygenase inhibitor3–10Platelet transfusion7 d
Clopidogrel (Plavix, Bristol-Myers Squibb Co and Sanofi-Aventis US LLC)Prevention and treatment of acute coronary syndrome;

secondary prevention of coronary artery and stent thrombosis;

treatment of peripheral arterial disease; prevention of TIA and CVA
Irreversible ADP receptor antagonist8Platelet transfusion (only partially effective)5–7 d
Prasugrel (Effient, Daiichi Sankyo, Inc and Eli Lilly and Co)Secondary prevention of coronary artery and stent thrombosisIrreversible ADP receptor antagonist7Platelet transfusion (only partially effective)5–7 d
Ticagrelor (Brilinta, AstraZeneca Pharmaceuticals, LP)Secondary prevention of coronary artery and stent thrombosis; treatment of peripheral arterial disease; prevention of TIA and CVAReversible and noncompetitive ADP receptor antagonist9Platelet transfusion (more effective)5–7 d

Summary of Guidelines for the Perioperative Management of Antithrombotic Medications

Table 2 Summary of Guidelines for the Perioperative Management of Antithrombotic Medications
Clinical areaGuideline
Preoperative thromboembolic risk stratification
 Nonvalvular atrial fibrillation thromboembolic riskStratify thromboembolic risk using the CHA2DS2-VASc score
 Prosthetic heart valve thromboembolic riskStratify risk according to valve type, location, and individual thromboembolic risk factors (atrial fibrillation, history of thromboembolism).
 Venous thromboembolism thromboembolic riskStratify based on time elapsed since VTE diagnosis and individual risk factors (cancer, thrombophilia); elective operation should be deferred for ≥3 mo after VTE diagnosis.
 Coronary artery disease coronary thromboembolism riskElective operation should be deferred for ≥14 d for balloon angioplasty, 30 d for bare-metal stent placement, and 1 year for drug-eluting stent placement.
 Stroke thromboembolic riskElective operation should be deferred for ≥9 mo after an ischemic stroke.
 Peripheral arterial disease thromboembolic riskPatients presenting for surgical evaluation who receive antithrombotic medication for symptomatic peripheral arterial disease should be managed in close consultation with a vascular specialist or vascular surgeon.
Procedural bleeding risk stratification
 Bleeding risk inherent to patient characteristicStratify risk using the HAS-BLED score.
 Bleeding risk inherent to the procedureLargely a subjective decision on behalf of the operating surgeon; most operations under the purview of the general surgeon will be classified as at least “low risk.”
Perioperative bridging therapy
 Antiplatelet therapyCurrently there is no evidence to suggest a benefit from the use of antiplatelet bridging therapy perioperatively.
 Direct oral anticoagulant therapyCurrently there is no evidence to suggest a benefit from the use of heparin bridging in patients taking DOACs.
Warfarin therapyUse for those classified as high VTE risk; discontinue warfarin 5 d before an elective procedure, and when the INR falls below the patient's therapeutic range, begin LMWH at a therapeutic dose until 24 h before the procedure; reinitiate warfarin 12 to 24 h after operation; reinitiate LMWH 48 to 72 h after operation.
Perioperative antithrombotic medication management strategy
 Unfractionated heparin
IntravenousHold 4 to 6 h before elective operation.
SubcutaneousHold 12 to 24 h before elective operation.
 Low-molecular-weight heparinHold 24 h before operation; resume 48 to 72 h after operation.
 WarfarinHold for 5 d before an elective operation; resume at previous dosing levels 12 to 24 h after operation.
 Dabigatran
Normal renal functionHold for 2 d before high bleeding risk operation and 1 day before low bleeding risk operation; resume 2 to 3 d after high-bleeding risk operation and 1 day after low bleeding risk operation.
Impaired renal functionHold for 4 d before high bleeding risk operation and 2 d before low bleeding risk operation.
 Rivaroxaban, apixaban, edoxabanHold for 2 d before high bleeding risk operation and 1 day before low bleeding risk operation; resume 2 to 3 d after high bleeding risk operation and 1 day after low bleeding risk operation.
 AspirinHold aspirin for 7 to 10 d before high bleeding risk operation in patients who have not had a percutaneous coronary intervention (PCI); resume when bleeding risk has diminished; in patients with recent PCI, consult with cardiologist.
 Clopidogrel, prasugrel, ticagrelorHold 5 to 7 d before low and high bleeding risk operation; resume when bleeding risk has diminished.
Consideration in the nonelective setting
 Vitamin K antagonistAdminister vitamin K and 4-factor PCC to patients with an elevated INR secondary to warfarin who are actively bleeding and/or require urgent operation.
 DabigatranAdminister idarucizumab to patients with evidence of significant dabigatran levels (by history of ingestion or laboratory parameter) who are bleeding or require emergency operation.
 Other DOACAdminister 4-factor PCC transfusion (50 units/kg) for partial reversal in patients with evidence of active factor Xa inhibitor as needed in emergency situation.
 Anti-platelet agentTransfuse 1 pooled unit of platelets immediately before operation and redose as needed for ongoing bleeding.

DOAC, direct oral anticoagulant; LMWH, low-molecular-weight-heparin; PCC, prothrombin complex concentrate; PCI, percutaneous coronary intervention; VTE, venous thromboembolism.


Risk-Stratification for Perioperative Thromboembolism
Risk categoryMechanical heart valveAtrial fibrillationVenous thromboembolism
HighMitral valve prosthesis; caged-ball or tilting disc aortic prosthesis;

stroke or TIA within 6 mo
CHA2DS2-VASc score ≥ 6; stroke or TIA within previous 3 mo; rheumatic valvular heart diseaseVTE within 3 mo; severe thrombophilia
ModerateBi-leaflet aortic valve prosthesis and at least one of the following risk factors: atrial fibrillation, previous stroke or TIA, hypertension, diabetes, congestive heart failure, age > 75 yCHA2DS2-VASc score 4 to 5 or previous stroke or TIA more than 3 mo beforeVTE within 3 to 12 mo; nonsevere thrombophilia†; recurrent VTE; active cancer
LowBi-leaflet aortic valve prosthesis and no other risk factors for strokeCHA2DS2-VASc score 2-3 (assuming no previous stroke or TIA)VTE > 12 mo previous and no other risk factor

Reference: https://www.journalacs.org/article/S1072-7515(18)31331-0/fulltext

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