Since DOACs exhibit a similar pharmacokinetic profile as LMWH, the use of parenteral bridging is generally not a recommended strategy for perioperative management. For high risk procedures, it is recommended that DOACs be held 3-5 half-lives to achieve maximal drug clearance.
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• Should patients on DOACs be perioperatively managed with LMWH and how long should DOACs be held for high risk procedures such as epidural pain injections?
• Should a patient with a history of recurrent VTE be bridged with LMWH?
Recent literature has shifted the landscape on how perioperative bridging should be approached. In most cases bridging with LMWH is associated with more risk of bleeding than prevention of VTE. Instances where bridging could be considered are:
1. Active cancer
2. Recent VTE (within 3 months)
3. Strong Thrombophilia (APS, protein C/S def or antithrombin deficiency)
4. Previous therapeutic failure or VTE during short term interruption
5. Patient undergoing procedure with high thrombotic risk
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• Should the dose of apixaban be reduced in the very elderly who do not meet two of the three dose reduction criteria (Age >80yo, sCr >1.5, <60kg WT)?
Recent publications have highlighted that “off-label” DOAC dose reductions correspond with higher incidence of thromboembolic events. Presently, “off-label” dose reductions should be avoided.
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• Should the dose of DOACs be reduced in patients who are prescribed amiodarone?
Amiodarone is a MODERATE interaction, and dose adjustment recommendations are in reference to strong interactions with the understanding that recommendations to reduce the dose are based on pharmacokinetic assumptions and not on hard data or experience in the trials.
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• Can DOACs be used for VTE treatment and secondary prevention in patients with Antiphospholipid syndrome?
It is best to avoid the use of DOACs in patients with APLS. Warfarin or LMWH should remain first line options until more data becomes available.
Recommendations from the International congress of Antiphospholipid Antibodies Task Force:
“The taskforce recommends that warfarin or other VKA remains the mainstay of anticoagulation in thrombotic APS. Oral direct inhibitors can be considered in APS patients with a first or recurrent VTE occurring off or on subtherapeutic anticoagulation, only when there is known VKA allergy/intolerance or poor anticoagulant control. There are no data to recommend ODI (oral direct inhibitors) in APS patients with recurrent VTE occurring on therapeutic anticoagulation or with APS-related arterial thrombosis”
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• Should an anticoagulated patient undergoing major orthopedic surgery (total hip or knee replacement) be perioperatively managed with low molecular weight heparin?
Recent studies such as the BRIDGE trial have demonstrated that there is a net harm associated with LMWH bridging. Consideration for bridging should be reserved for patients who are at high risk for thromboembolism such as:
1. Patients with any thromboembolism during past interruptions of anticoagulation, or while on therapeutic anticoagulation
2. Patients with a cerebrovascular accident or transient ischemic attack in the past 3 months
3. Patients with recent (within 1 month) evidence of mural thrombus or left atrial appendage clot
4. Patients with a mitral mechanical valve
5. Patients with older caged ball or tilting disc mechanical valves
6. Patients with VTE in the past 3 months
7. Patients with VTE and a properly diagnosed hypercoagulable state, including antiphospholipid antibody syndrome,
8. Protein C or Protein S deficiency, or antithrombin3 deficiency.
9. CHADS2 score of 5-6 or CHADS2VASc score of 7-9
Additional guidance is available from the American College of Cardiology at:
American College of Cardiology Periprocedural Guidance
In patients undergoing major orthopedic surgeries who do not require bridging, it is still necessary to consider post-operative VTE prophylaxis, due to the high risk of thromboembolism associated with major orthopedic surgeries, until full dose anticoagulation is cleared by the orthopedic surgeon.
In very high risk patients in whom full dose bridging is deemed necessary, it is recommended risks and benefits be discussed with the proceduralist to determine the best course of action for the patient.
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• Can DOACs be used in superficial vein thrombosis?
The CHEST guidelines provide recommendations for lower extremity SVT (not upper). If the SVT is >5cm, recommendations are to utilize prophylactic dosing of fondaparinux.
Patients with superficial venous thrombosis of the lower limb of at least 5 cm in length. Suggest the use of a prophylactic dose of fondaparinux or LMWH for 45 days over no anticoagulation.
Currently, none of the DOACs have FDA approval to treat SVT, however a recent study showed a 45 day course of rivaroxaban 10mg was noninferior to fondaparinux at preventing serious complications in high risk SVT.
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• When should anticoagulation be restarted after a GI bleed?
Literature suggests patients who have experienced warfarin associated GIB, the benefits of resuming anticoagulant therapy will outweigh the risks (RETREAT). While the data varies as to exactly when anticoagulation should be restarted, available evidence indicates that waiting ∼14 days may best balance the risk of recurrent bleeding, thromboembolism, and mortality after gastrointestinal tract bleeding (WITT ASH Education Book December 2, 2016 vol. 2016 no. 1 620-624).
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