General Considerations for Periprocedural Anticoagulation
When evaluating a patient on anticoagulation during the periprocedural period, it is important to review the bleeding risk, both for the procedure and the individual patient, and the thromboembolic risk of the patient. The bleeding risk guides how early to hold anticoagulants prior to the procedure and how long to wait after the procedure to restart anticoagulation. The same patient at high thrombotic risk may require the use of bridging anticoagulation prior to the procedure and, in certain instances, early resumption of anticoagulation after the procedure. The anticoagulant the patient is using may also affect the timing of the procedure to allow for bleeding risk to reach a safe margin. For example, due to the short half-life of heparin IV infusion, using this anticoagulant may decrease the time needed to wait prior to the procedure, whereas using direct oral anticoagulants (DOACs) requires a much longer delay. Lastly, the nature of the procedure, emergent vs elective, should also be considered to weigh the benefits of the procedure against the risk of bleeding and thrombosis.
The exact management of anticoagulation during this period is a balance between the risk of bleeding and the risk of thrombosis. It is important to remind the reader that most of the research and the recommendations found in the ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients with Nonvalvular Atrial Fibrillation guideline are directed toward the management of patients on anticoagulation for atrial fibrillation (AF). In this chapter, the anticoagulant management strategies certainly apply to patients with AF and may apply or may be modified to apply to expanded patient groups as well. Lastly, use of these anticoagulant management strategies will play a significant role in the outcomes during the periprocedural period.
Evaluating Bleeding Risks
Procedure bleeding risks are categorized as low, intermediate, or high and are affected by intricacies such as the level of vascularization at the area of manipulation and the implications of bleeds in that space (e.g., intraspinal/epidural spaces). These bleeding risks are largely driven by expert opinion, as there is a lack of large observational data for most procedures. Nevertheless, common procedures along with their bleeding risk category are available on the online appendix copublished with the ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients with Nonvalvular Atrial Fibrillation. Patient-specific bleeding risks assess the likelihood of bleeding with patient-specific risk factors such as advanced age, hypertension, history of bleeding (increased risk if <3 months from last bleed or bleeding from similar procedure or bridging), liver or renal disease, thrombocytopenia or platelet dysfunction (e.g., uremia), history of stroke, labile or supratherapeutic international normalized ratio (INR), antiplatelet or nonsteroidal anti-inflammatory drug use, or alcohol use. Several risk scores have been studied and developed to assist in quantifying patient-specific bleeding risks, including the HAS-BLED, ATRIA, HEMORR2HAGES, and SAMe-TT2R2 scores. However, a high bleeding risk based on these scores does not directly affect the management of periprocedural anticoagulation because these risk scores may better serve to aid in identifying reversible risk factors that can be attenuated to reduce the patient-specific bleeding risk.
Although major bleeding risks between prophylactic- and therapeutic-dose parenteral anticoagulants are not as different as one would expect, the clinically relevant nonmajor bleeding risks are not well documented. When evaluating a patient’s anticoagulant regimen for bleeding risk, it would still be prudent to consider therapeutic-dose anticoagulation to be a higher risk of a bleed compared with prophylactic-dose anticoagulation.
EVALUATION AND MANAGEMENT OF ANTIPLATELET AGENTS
When caring for patients entering the periprocedural period, careful medication reconciliation must be performed, and any antiplatelet use should be identified because these agents may contribute to the patient’s overall bleeding risk. However, there remains a relative lack of rigorous guidance regarding management of antiplatelet therapy in the periprocedural period, mainly due to the paucity of good clinical trial data. The limited data that is available suggests continuing aspirin for secondary prevention of cardiovascular diseases for most common procedures performed during a modern-day medicine service, such as , :
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Arthrocentesis
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Lumbar punctures
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Paracentesis
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Thoracentesis
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Central venous catheter placements
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Diagnostic gastrointestinal procedures
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Endoscopic retrograde cholangiopancreatography (ERCP) with stent placement
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Percutaneous endoscopic gastrostomy (PEG) placement
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Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA)
Dual antiplatelet therapy confers higher bleeding risk. Therefore, procedures with higher risk of bleeding or risk of a life-threatening bleed will generally require the P2Y 12 inhibitor to be held and potentially substituted with aspirin, if the patient is not already on aspirin. , Ultimately, the decision to continue or withhold antiplatelet therapy is made after carefully assessing important bleeding risk factors such as tissue injury during the procedure, proximity of the procedure to vital organs or vascular structures, whether bleeding can be readily detected and controlled, and the associated morbidity of a bleed (e.g., small bleed in a noncompressible space vs small bleed in an open space). In the event P2Y 12 inhibitors need to be held, ticagrelor and clopidogrel should be held 5 days and prasugrel 7 days prior to a procedure with major bleeding risks. Because of the irreversible nature of most P2Y 12 inhibitors, the lengthier hold period for these agents are to allow time for regeneration of enough unaffected platelets to support a high bleeding risk procedure.
HALF-LIFE AND TIMING OF ANTICOAGULANTS
Another point to consider when evaluating a patient’s procedural bleed risk is the half-life of the anticoagulant and timing of the last dose. The half-life of each anticoagulant dictates the time period that should elapse prior to the procedure. Warfarin is an exception, as the regeneration of thrombin is the rate-limiting step in limiting procedural bleed risk. Nevertheless, the passing of each half-life allows for the elimination of 50% of the anticoagulant. Therefore, only 12.5% of theanticoagulant remains after 3 half-lives, while only 3.125% of the anticoagulant remains after 5 half-lives. This strategy is particularly important when managing DOACs in the preprocedural period, when 2–3 half-lives should elapse prior to low–bleed risk procedures and 4–5 half-lives for intermediate– and high–bleed risk procedures, an approach that was adopted by the PAUSE trial, which studied the periprocedural management of DOACs. , See Table 4.1 for DOAC half-lives.
| Medication | Half-Life (Hours) |
|---|---|
| Dabigatran | 13 |
| Apixaban | 12 |
| Rivaroxaban | 5–9 |
| Edoxaban | 10–14 |
Knowledge of when the last dose was administered allows the practitioner to determine whether the patient is approaching peak anticoagulant activity or the end of the duration of action of the anticoagulant. This approach has been incorporated into the design of the PAUSE trial and is particularly important for subcutaneous anticoagulants with short half-lives such as unfractionated heparin (UFH) and low–molecular weight heparins (LMWH). The concept is used in the ASRA Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy guidelines, which suggest performing neuraxial procedures at the end of the dosing period for patients administered prophylactic doses of heparin and avoiding such procedures near the peak effect of prophylactic doses of LMWH.
LABORATORY MEASUREMENT OF ANTICOAGULANT ACTIVITY
When the timing of the last dose of the anticoagulant is unclear, as commonly happens in the emergency department, anticoagulant activity may be measured to guide the decision-making process for emergency procedures. INR remains the standard for which warfarin activity is measured, and an INR of <1.5 is generally accepted as the threshold for procedures, whereas LMWH activity is measured using an anti-Xa assay. The measurement of DOAC activity is less straightforward because it is dependent on whether specialized assays are available at each institution. When specialized assays with rapid turnaround times are available, dilute thrombin time, ecarin clotting time, or ecarin chromogenic assay should be used to measure dabigatran, and chromogenic anti-Xa assay calibrated for apixaban, rivaroxaban, and edoxaban should be used to measure these DOACs prior to an emergent procedure. When only the standard anti-Xa assay (calibrated to LMWH) is available, it may be used to exclude clinically relevant levels of apixaban, rivaroxaban, and edoxaban. Normal levels or the absence of activity of these specialized assays suggests that the concentration of DOAC is not a clinically relevant contributor to surgical bleed risk, whereas patients with high bleeding risk and a DOAC level of >30 ng/mL may require appropriate reversal.
When specialized assays are not available, normal thrombin time or activated partial thromboplastin time (aPTT) will usually exclude clinically relevant levels of dabigatran, whereas normal prothrombin time (PT) or aPTT are unreliable in excluding clinically relevant levels of apixaban, rivaroxaban, or edoxaban. Patients with prolonged aPTT on dabigatran or prolonged PT on the remaining DOACs are considered to have at least on-therapy levels of DOACs affecting the clotting cascade. These suggestions are summarized in Table 4.2 .
| Anticoagulant | Exclude Clinically Relevant Levels | Does Not Exclude Clinically Relevant Levels | Includes Clinically Relevant Levels |
|---|---|---|---|
| Dabigatran | Normal TT or aPTT | N/A | Prolonged aPTT |
| Other DOACs a | N/A | Normal PT or aPTT | Prolonged PT |
a Includes apixaban, rivaroxaban, and edoxaban. aPTT, activated partial thromboplastin time; DOACs, direct oral anticoagulants; PT, prothrombin time; TT, thromboplastin time.
REVERSIBILITY OF ANTICOAGULANTS
In the event a patient requires reversal of an anticoagulant to facilitate an emergency procedure with a high bleeding risk, knowledge of the availability and reliability of the reversal agent is of utmost importance. This is described in Table 4.3 . The reversal of therapeutic doses of UFH and LMWH may be achieved using protamine. Given the incomplete reversal of anticoagulant effects of LMWH with protamine, therapeutic UFH may be a better option in situations in which an emergency procedure is likely.
| Anticoagulant | First Line | Second Line |
|---|---|---|
| Apixaban | 4FPCC | aPCC |
| Rivaroxaban | 4FPCC | aPCC |
| Edoxaban | 4FPCC | aPCC |
| Dabigatran | Idarucizumab | aPCC or 4FPCC |
| Warfarin | 4FPCC | Plasma |
| IV UFH | Protamine | N/A |
| LMWH | Protamine | N/A |
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