Jourdan M. Cancienne, Brian C. Werner.

Response/Recommendation:

Perioperative management of patients on warfarin and those with conditions placing them at high risk for venous thromboembolism (VTE) remains challenging. Patients on warfarin undergoing elective orthopaedic surgery should not routinely be bridged with unfractionated heparin (UFH) or low-molecular-weight heparin (LWMH) as several studies identify a significant increase in bleeding-related complications during this time period. In patients with comorbid conditions, such as a mechanical heart valve, where risks of thromboembolic events may outweigh the risk of bleeding, bridging to warfarin should be considered.

Strength of Recommendation: Limited.

Rationale: Management of patients who require long-term oral anticoagulation with warfarin due to conditions causing a high-risk for VTE is challenging in the perioperative period of elective total joint arthroplasty (TJA) surgery^1–4.  In order to balance the risks of VTE with cessation of warfarin, and the increased bleeding risks of continuing it, bridging chemoprophylactic agents are commonly utilized. The decision to bridge a patient is typically made by the treating surgeon based on the patient’s individual risk for VTE. Although multiple studies outside of the orthopaedic literature have investigated the effect of bridge therapy in vascular and general surgery, extrapolating such data to assess a patient’s individual complication risk for total knee arthroplasty (TKA) and total hip arthroplasty (THA) is difficult¹. Furthermore, little data is available that focuses on specific thromboembolic and bleeding-related complications in patients undergoing TJA who are bridged to warfarin to help guide decision-making.

Haighton et al., performed a retrospective cohort study of all patients undergoing primary THA or TKA in a 4-year period who underwent bridging therapy with either therapeutic UFH or LMWH according to a protocol and were compared to patients who received standard postoperative prophylactic LMWH postoperatively². Patients on bridging therapy had a significantly higher complication risk compared to patients receiving standard thrombosis prophylaxis.  The majority of complications were bleeding-related, and no thromboembolic events were reported in either bridging group. The group concluded that the risks of bleeding and thromboembolic complications have to be carefully balanced and patients must be counseled ad monitored postoperatively.

Simpson et al., performed a similar retrospective study examining 32 patients on chronic warfarin who were bridged with heparin perioperatively and compared them to patients treated with warfarin and other chemoprophylactic agents without bridging³. Patients who were bridged experienced significantly higher rates of deep infection and excessive wound drainage. Ultimately the authors’ concluded that going forward, the challenge will be to identify which patients on chronic warfarin treatment can do without therapeutic anticoagulation perioperatively. In those patients who require bridging therapy, such as those with prosthetic valves or pro-coagulant disorders, the goal will be to optimize the risks of thrombosis with the bleeding and infection risks of surgery. Furthermore, there are two large multi-center randomized trials being conducted to examine the safety and efficacy of bridging therapy with LMWH in high-risk and low-risk patients respectively³. However, at this time it is incumbent upon the orthopaedic surgeon in conjunction with the consultants to weigh the risk of thrombosis versus bleeding and infection for each patient in order to determine the optimal perioperative anticoagulant regimen.

Jørgensen et al., studied 649 patients on vitamin K antagonist treatment undergoing THA and TKA⁵. Of these, 430 patients were bridged, and 215 patients had their vitamin K antagonist paused. No statistically significant differences were found in regard to arterial or venous thromboembolic events or major bleeding events. However, there was a higher number of thromboembolic events in paused patients and a higher number of major bleeding events in bridged patients.

Leijtens et al., identified 13 patients receiving LMWH bridging during THA or TKA according to the American College of Clinical Pharmacy guidelines⁴. Of these, 12 patients experienced bleeding complications with an intervention required in nine. Seven patients required a blood transfusion, nine a developed hematoma, and two periprosthetic joint infection. However, no thromboembolic were observed in any patients. This study demonstrated an alarmingly high complication rate in patients being bridged with LMWH bridging during elective TJA surgery, with all complications related to bleeding.

The study of bridging anticoagulation as it relates to THA and TKA is somewhat limited, however, in the broader medical literature, there have been more inquiries into its efficacy1. Multiple recent studies evaluating bridging strategies have found that major bleeding occurs more frequently than VTE, and that the bleeding to thrombosis ratio is 13:1 in patients who are bridged as compared to 5:1 in those without bridging1. While major bleeding may be acceptable in order to avoid VTE, there is currently no evidence of a meaningful decrease in thromboembolic events when bridging is used. However, this data is admittedly somewhat limited as it does not stratify the VTE rates in low- vs. high-risk patients. With the known increased risk of thromboembolic events in patients without anticoagulation, it is not acceptable to abort bridging strategies altogether, especially in patients with high-risk conditions. Rather, the decision should be on an individualized level with a multi-disciplinary effort.

References:

1.         Tan CW, Wall M, Rosengart TK, Ghanta RK. How to bridge? Management of anticoagulation in patients with mechanical heart valves undergoing noncardiac surgical procedures. J Thorac Cardiovasc Surg. 2019;158(1):200-203. doi:10.1016/j.jtcvs.2018.06.089

2.         Haighton M, Kempen DHR, Wolterbeek N, Marting LN, van Dijk M, Veen RMR. Bridging therapy for oral anticoagulation increases the risk for bleeding-related complications in total joint arthroplasty. J Orthop Surg Res. 2015;10:145. doi:10.1186/s13018-015-0285-6

3.         Simpson PMS, Brew CJ, Whitehouse SL, Crawford RW, Donnelly BJ. Complications of perioperative warfarin therapy in total knee arthroplasty. J Arthroplasty. 2014;29(2):320-324. doi:10.1016/j.arth.2012.11.003

4.         Leijtens B, Kremers van de Hei K, Jansen J, Koëter S. High complication rate after total knee and hip replacement due to perioperative bridging of anticoagulant therapy based on the 2012 ACCP guideline. Arch Orthop Trauma Surg. 2014;134(9):1335-1341. doi:10.1007/s00402-014-2034-4

5.         Jørgensen CC, Kehlet H, Lundbeck Foundation Center for Fast-Track Hip and Knee Replacement Collaborative Group. Thromboembolic and major bleeding events in relation to perioperative bridging of vitamin K antagonists in 649 fast-track total hip and knee arthroplasties. Acta Orthop. 2017;88(1):55-61. doi:10.1080/17453674.2016.1245998