Most of the guidelines are similar in recommending the classification of surgical timing, surgical bleeding risk, patient bleeding risk, and patient thromboembolism risk before deciding on an antithrombotic agent management plan. The AAOS guidelines classify surgical timing as urgent (surgery necessary within 24 h), semi-urgent (within 24 to 72 h), or elective. We will only be discussing the management of elective TJAs in this review, but in general for urgent and semi-urgent procedures, the reversal of anticoagulation is recommended prior to surgery. We refer the reader to other reviews on the management of antithrombotic agents for hip fracture surgery [41]. For elective TJAs, the AAOS guidelines consider the risk of post-operative hemorrhage for the TJA to be intermediate, which is consistent with other guidelines that suggest it is intermediate or high risk. This classification is largely subjective, but we agree with the AAOS guideline determination.

After establishing the surgical timing and surgical bleeding risk, the patient can then be stratified based upon their individual thromboembolism and bleeding risk to make specific antithrombotic management decisions. Thromboembolism risk is classified by multiple guidelines as either high, intermediate, or low, typically based upon the patient’s CHADS₂ [42] or CHA₂DS₂-VASc score [43], prior VTE history, the presence of any heart valves or stents, and other medical risk factors (Table 1). The determination of patient bleeding risk post-operatively is more difficult. The ACC recommends considering the patient’s HAS-BLED score [44], which was developed for assessing bleeding risk in the context of atrial fibrillation. The guidelines note that it is predictive of periprocedural bleeding, but not validated for this purpose. Other elements of the patient’s medical history should be considered when assessing the bleeding risk, such as prior bleeding history and laboratory tests (Table 2). Any risk factors should be mitigated to whatever extent possible prior to surgery.

There is a high degree of consensus among the AAOS, ACCP, ACC, ASRA, and ACS guidelines regarding the perioperative management of warfarin, with minor differences in timing and INR (international normalized ratio) targets. Patients on warfarin undergoing an elective TJA should have warfarin discontinued 5 days before surgery, with a target INR of ≤1.3 according to AAOS, or <1.5 according to ACCP, ASRA, and ACS measured the day before surgery. In refractory cases, vitamin K is recommended as an adjunct to normalize the INR, which typically avoids the need to delay surgery. AAOS recommends oral vitamin K over intravenous (IV) or intramuscular forms; ACCP also recommends oral vitamin K (1 to 2.5 mg), while ACS suggests 1.0 mg IV. The ACC guidelines propose the timing of warfarin interruption based upon INR targets measured 5 to 7 days pre-operatively, interrupting ≥5 days before surgery if the INR is >3.0, 5 days before for INR between 2.0 to 3.0, and 3 to 4 days before for INR 1.5 to 1.9. In any case, individual decisions should be made for patients on higher warfarin maintenance doses or if the INR is known to normalize quickly. According to AAOS, ACCP, ACC, and ACS, warfarin can be resumed at the normal dose the evening of or the morning after surgery if adequate hemostasis has been achieved (12 to 24 h later).

Whether to bridge warfarin with other anticoagulants pre-operatively after its interruption, or post-operatively prior to its re-initiation requires further consideration. The guidelines vary in whether or not they recommend a specific bridging regimen when bridging is indicated. The AAOS guidelines recommend outpatient LMWH for bridging, largely due to its efficacy and cost-effectiveness, unless the patient is pregnant or has renal failure, in which case unfractionated heparin (UFH) is recommended. Other guidelines, such as those by the ACCP, do not recommend specific bridging regimens. According to ACCP, examples of bridging regimens include, for therapeutic dosing: enoxaparin 1 mg/kg BID (twice per day) or 1.5 mg/kg daily; dalteparin 100 IU/kg BID or 200 IU/kg daily; tinzaparin 175 IU/kg daily; IV UFH to achieve an aPTT (activated partial thromboplastin time) target of 1.5 to 2 times control; or SC heparin 250 IU/kg BID without aPTT monitoring; and for prophylactic dosing: enoxaparin 30 mg BID or 40 mg daily; dalteparin 5000 IU daily; or UFH 5000–7500 IU BID.

There is consensus from the AAOS, ACCP, ACC, ASRA, and ACS guidelines that a patient’s thromboembolism risk stratification dictates the need for post-operative bridging for patients on warfarin. For patients with a high risk of thromboembolism (>10% risk per year) and CHA₂DS₂-VASc 7–9, bridging, such as with therapeutic LMWH (1 mg/kg BID), is recommended when the INR is subtherapeutic (generally <1.8 according to AAOS; in non-valvular atrial fibrillation, the ACC guidelines recommend bridging when the INR is <2.0). LMWH should be stopped 24 h before surgery, while UFH should be stopped 4 to 6 h pre-operatively. If the patient is also at high bleeding risk, clinical judgment in consultation with vascular medicine, cardiology, and/or anesthesia is recommended regarding the need to bridge, bridging strategy, or if an inferior vena cava (IVC) filter is indicated. Warfarin can be resumed the evening after surgery at the pre-operative maintenance dose; a loading dose is not recommended by the AAOS or ACC guidelines. For intermediate or low bleeding risk, a bridge with therapeutic LMWH can begin when wound hemostasis is achieved (typically within 24 to 48 h of surgery) and stopped when the INR is therapeutic (AAOS recommends INR ≥ 1.8, ACC recommends >2.0 for non-valvular atrial fibrillation). For patients at a high bleeding risk, the guidelines present a few options: a bridge with prophylactic dose LMWH (30–40 mg subcutaneous BID) can be considered according to AAOS, bridging could be delayed to 48 to 72 h post-operatively according to ACS, or in some scenarios it may be better not to bridge according to ACC.

For patients with an intermediate risk of thromboembolism (5% to 10% risk per year) and CHA₂DS₂-VASc 5 to 6, the AAOS, ACCP, and ACS guidelines recommend clinical judgement as to whether or not to bridge with therapeutic anticoagulants. The AAOS guidelines suggest that an IVC filter can be considered in this scenario. The ACC guidelines offer more specific guidance, informed in part by the randomized controlled BRIDGE (Bridging Anticoagulation in Patients Who Require Temporary Interruption of VKA Therapy for an Elective Invasive Procedure or Surgery) trial [45]: if the patient is at a high bleeding risk, bridging should typically be avoided, while if they are at a lower bleeding risk but have a history of stroke, transient ischemic attack (TIA), or systemic embolization, bridging is typically indicated. Regardless, in this scenario prophylactic antithrombotic agents are recommended for VTE prophylaxis, such as LMWH, until 12 h prior to surgery and restarted the night of surgery until the INR is therapeutic.

For patients with a low risk of thromboembolism (<5% risk per year) and CHA₂DS₂-VASc ≤ 4, bridging is not recommended by the AAOS, ACCP, ACC, or ACS guidelines. Pharmacologic VTE prophylaxis is still indicated as for the intermediate thromboembolism risk group.

The ASRA guidelines apply to surgeries being performed under spinal anesthesia. In some centers, the TJA is performed under spinal anesthesia instead of general anesthesia. These guidelines were first published in 2012 and updated in 2018. Due to the anatomy of the spinal canal, even a small amount of bleeding that results in a spinal hematoma can cause significant morbidity, which makes neuraxial anesthesia a high bleeding risk procedure. For warfarin, the ASRA guidelines recommend an INR target of <1.5 before inserting or removing a spinal catheter. UFH should be discontinued 4 to 6 h prior to a spinal block or prior to catheter removal, with normal coagulation studies verified, similar to TJA. Patients may be re-heparinized one hour after placement or removal. Prophylactic dose LMWH should be discontinued 12 h before and therapeutic dose of LMWH 24 h before catheter insertion or removal, again similar to TJA. The re-initiation of prophylactic LMWH should be delayed at least 12 h after catheter placement and 4 h after removal, while therapeutic LMWH should be delayed 24 to 72 h after catheter placement depending on the bleeding risk.

Only the ACC, ACS, and ASRA guidelines discuss the perioperative management of chronic direct oral anticoagulant (DOAC) therapy. DOAC management is typically simpler than the management of warfarin, mainly due to their shorter half-lives, shorter interruption intervals, and because laboratory monitoring is not required. The exact timing for DOAC interruption depends on the agent’s half-life and the patient’s renal function (Table 3). For therapeutic dosing, holding DOACs for a 4 to 5 half-life interval is recommended by the ACC guidelines before beginning an intermediate or high bleeding risk procedure such as a TJA, while a 2 to 3 half-life interval is acceptable for patients on prophylactic dosing. For the re-initiation of DOAC therapy, the ACC recommends waiting 24 to 72 h post-operatively (depending on the patient bleeding risk) and for wound hemostasis to be achieved, at which point therapy can be resumed at the full prior dose, without a loading dose. For low patient bleeding risk where a DOAC is being re-started within 24 h of the procedure, a reduced initial dose can be considered according to the ACC guidelines.

DOAC interruption generally does not require bridging due to the short half-lives of these medications. In the scenario where a patient is at a high post-operative bleeding risk, needs another procedure, or cannot yet tolerate oral medications, the ACC guidelines propose that UFH or LMWH may be temporarily used to bridge to a DOAC, though this is an uncommon scenario.

Most DOACs carry a black box warning for spinal epidural hematoma in the setting of neuraxial anesthesia, lending special consideration for their use in TJAs performed under spinal anesthesia. The ASRA guidelines recommend interruption of Factor Xa inhibitor therapy (apixaban, edoxaban, and rivaroxaban) for 72 h prior to catheter insertion, and that the catheter be removed at least 6 h before the first post-operative dose (Table 3). For dabigatran, a 72-h interruption interval may be used for patients with normal renal function (creatinine clearance (CrCl) ≥ 80 mL/min), but longer intervals are recommended in the setting of reduced renal function (Table 3).

The ASRA guidelines also present interruption intervals for unanticipated procedures, which generally does not apply to elective TJAs. A prior review has suggested that the interruption intervals presented by ASRA for the prophylactic dosing of DOACs in unanticipated neuraxial procedures be used to guide management in TJAs, though we disagree given that an elective TJA is planned and therapeutic DOAC dosing is typically used for chronic anticoagulation [46]. If shorter intervals are being considered for any of the DOACs, a dilute thrombin test (dTT, for dabigatran) or anti-Xa level (for the Factor Xa inhibitors) can be considered.

There is generally consensus among the AAOS, ACCP, ACC, and ACS guidelines on the pre-operative intervals at which to hold aspirin and the antiplatelet agents (clopidogrel, prasugrel, and ticagrelor). For most patients, aspirin should be discontinued 7 to 10 days pre-operatively and the anti-platelet agents 5 to 7 days pre-operatively. The ACCP guidelines recommend that patients at moderate or high cardiovascular risk undergoing surgery continue aspirin perioperatively. Similarly, the ACS guidelines recommend holding aspirin pre-operatively so long as there is no history of percutaneous coronary intervention (PCI).

For patients who have undergone cardiac stenting, surgery should be delayed at least 6 months after a drug-eluting stent and at least 3 months for bare-metal stents, according to the 2010 AAOS guidelines. At this point, aspirin and the antiplatelet agents may be discontinued as above, and restarted when post-operative hemostasis has been achieved.

In the case of procedures performed under spinal anesthesia, the ASRA guidelines recommend a 5 to 7 day pre-operative interruption interval for clopidogrel and ticagrelor, but 7 to 10 days for prasugrel. Antiplatelets can be restarted 24 h post-operatively, or immediately after catheter removal so long as a loading dose is not being used.