201 – What is the optimal management of patients on antiplatelet and/or anticoagulation presenting with acute lower extremity trauma and needing surgery?

201 – What is the optimal management of patients on antiplatelet and/or anticoagulation presenting with acute lower extremity trauma and needing surgery?

Radoicic Dragan, Francisco Chana-Rodríguez, Antonio Benjumea-Carrasco, Jesús Gómez-Vallejo.

Response/Recommendation: The optimal management of patients on antiplatelets and/or anticoagulants presenting with acute lower extremity trauma and needing surgery should involve a risk-benefit assessment weighing the risk of bleeding against the risk of thrombosis. Depending on the degree of urgency, extent of trauma and patient’s coagulation status, the optimal approach may involve postponing the procedure and monitoring the coagulation status, perioperative bridging therapy, or acute reversal of anticoagulation.

            Most studies recommend that patients receiving aspirin (ASA) can undergo surgery safely without delay. In patients taking oral anticoagulants, coagulation tests should be performed. If surgery cannot be delayed, anticoagulant reversal agents should be administered. Recent literature has suggested that the use of reversal agents does not lead to adverse outcomes following lower extremity trauma surgery. In addition, early surgical treatment of hip fractures despite anticoagulation may be prudent in a subgroup of patients.

Strength of Recommendation: Limited.

Rationale: Antithrombotic agents can be broadly subdivided into two classes: anticoagulants and antiplatelet medications1,2. When patients on these agents undergo orthopaedic procedures, management should entail an individualized assessment of the risk of bleeding as well as the risk of thrombosis. Approximately 1 in 10 surgical patients are prescribed chronic anticoagulation or antiplatelet therapy, and majority will require temporary antithrombotic interruption, bridging, or reversal1,3–5. It is widely established that urgent, non-deferrable surgery should not be delayed in patients on antiplatelets, even in those receiving dual antiplatelet therapy6,7. In contrast, given the wide variety of anticoagulation agents available8, there is substantial heterogeneity with regards to the perioperative management of these patients. Not surprisingly, there is still a lack of consensus on this topic within the orthopaedic community9.

The majority of recommendations regarding the interruption of anticoagulant or antiplatelet therapy in trauma patients with a moderate to high risk of bleeding are reflected in the latest clinical guidelines of various professional societies6,10,11. These strategies have largely been developed from general surgical and neurosurgical literature12. As existing guidelines are based on expert opinion, consensus, and retrospective studies, the level of evidence is extremely limited. In addition, most recommendations have been restricted to the safety of neuraxial anesthesia rather than trauma surgery per se6,10,13.

Recent data has shown that hip fracture patients are prone to prolonged elimination half-lives of direct oral anticoagulants (DOAC), with almost 50% of patients still having therapeutic levels at the time of surgery14. Patients on DOAC have increased delays to surgery compared to patients who are not on anticoagulation or those on vitamin K antagonists. The average time to surgery for DOAC patients may range from 35.0 hours to 66.9 hours15,16. King et al.17, concluded that taking DOAC on admission was not a reason to delay hip fracture surgery. Similarly, Bruckbauer et al.18, suggested that early hip fracture surgery should be indicated in DOAC patients. Consistent with these findings, Schuetze et al.19, noted that early surgical care of proximal femur fractures was safe in patients on anticoagulants, as long as preparations for possible intraoperative transfusions were made. In contrast, Gosch et al.20, found that hip fracture patients on oral anticoagulation had higher rates of in-hospital mortality, transfusion (requiring 3 or more packed red cells), major bleeding, hemoglobin drop of 6 g/dL or more, myocardial infarction, stroke, and thromboembolic events, compared to controls who were not on anticoagulation.

Besides hip fractures, data on the management of other lower extremity fractures in patients on antiplatelet or anticoagulation remains scarce. Recent literature has demonstrated a trend away from the routine use of bridging anticoagulation21, with several reports suggesting that the administration of reversal agents may not lead to adverse outcomes in lower extremity trauma surgery22. Ultimately, the risks associated with delaying operative care in lower extremity trauma is fracture- and patient-specific. Depending on the degree of urgency, extent of trauma, and patient’s coagulation status, the optimal approach may involve postponing the procedure and monitoring the coagulation status, perioperative bridging therapy, or acute reversal of anticoagulation.

The following recommendations are brief excerpts from current guidelines and recent literature, which provide an update on the most common antithrombotic reversal strategies or corrective measures. These strategies should be carried out in collaboration with cardiology, anesthesiology, and other specialties.

Warfarin: There is an ongoing debate regarding the perioperative management of trauma patients on warfarin. Some authors advocate a watch-and-wait approach, while others recommend urgent reversal. It is well established that fracture surgery can be expedited by reversing the anticoagulation effect of warfarin with vitamin K23,24. The National Institute for Health and Care Excellence (NICE) guidelines have underscored the importance of prompt surgical management of elderly patients with hip fractures within the first 36 hours, reiterating that delays related to anticoagulation are often unjustified25. Gulati et al.26, and Moores et al.27, advised that the action of warfarin should be reversed in order to expedite hip fracture surgery. This reversal can be achieved with vitamin K, prothrombin complex concentrate ([PCC] Beriplex), fresh frozen plasma (FFP), or recombinant factor VIIa4,28.

For surgeons adopting a watch-and-wait approach, the 2017 American College of Cardiology (ACC) guidelines recommended checking the international normalized ratio (INR) 5 to 7 days before surgery. The INR should then be rechecked within 24 hours of surgery to ensure normalization. Bridging anticoagulation, typically with low-molecular-weight heparin (LMWH), is undertaken in patients at high thrombotic risk, which has been defined as patients with a Congestive heart failure, Hypertension,

Age ≥ 75 years, Diabetes mellitus, prior Stroke or transitory ischemic attack (TIA) or thromboembolism – Vascular disease, Age 65 – 74 years, female Sex category (CHA2DS2-VASc) score of ≥ 7 (greater than 10% annual risk of stroke or embolism) or patients with a thrombotic event within the past 3 months2.

Dabigatran: For procedures with high bleeding risk, ACC guidelines recommend an antithrombotic interruption (ATI) period of 2 days before surgery without the need for bridging anticoagulation. In patients with impaired renal function (creatinine clearance < 50 mL/min), a longer ATI duration of 4 days is recommended2. The fourth edition of the American Society of Regional Anesthesia (ASRA) guidelines suggest only a 34-hour ATI interval before neuraxial block, and 72 to 90 hours in patients with renal impairment29.

In the event of overdose, its effect can be reversed with hemodialysis and antidote administration using idarucizumab (Praxbind)30. The approved dose is two 2.5 g IV bolus infusions administered within 15 min1. In life-threatening bleeding, this can be combined with tranexamic acid (TXA) (1 g. IV). PCC is another option, although there is limited evidence regarding its use in patients on DOAC. The use of FFP is currently restricted to rescue therapy if other alternatives are not available13,31.

Low-molecular-weight heparin (LMWH): For patients on treatment doses of LMWH, surgery under neuraxial anesthesia should be delayed for at least 24 hours. For patients on prophylactic doses of LMWH, this delay can be reduced to 12 hours10.

Oral anticoagulants should be discontinued prior to procedures with a moderate to high risk of bleeding including long bone fractures and hip fractures6. In patients with a low to moderate thrombotic risk, perioperative bridging therapy may not be necessary. However, for patients with a high thromboembolic risk, bridging therapy with LMWH at prophylactic doses can be administered. If urgent surgery is indicated, the use of reversal agents should be considered6,31.

Rivaroxaban: The ACC guidelines recommend a discontinuation period of 2 days before high-risk procedures, with a longer ATI period of 3 days in the setting of renal impairment. The ASRA guidelines recommend discontinuing rivaroxaban 22 to 26 hours before neuraxial block except in the setting of renal impairment, in which case 44 to 65 hours is recommended29.

Rivaroxaban is not removed by hemodialysis. Andexanet alfa (AndexXa) is the first and only antidote for patients taking rivaroxaban (Xarelto), apixaban (Eliquis) or edoxaban (Savaysa)32. Activated charcoal may help to reduce absorption in cases of acute over-ingestion of DOAC and should be administered within 1 – 2 hours of novel oral anticoagulants (NOAC) intake33.

Apixaban: The ACC recommends an ATI period of 2 days. As 27% of the drug is renally cleared, a longer ATI of 3 days is recommended in the setting of renal impairment2. The ASRA guidelines recommend discontinuing apixaban 26 to 30 hours before neuraxial procedures, and 40 to 75 hours in patients with a serum creatinine of 1.5 mg/dL or more29.

Edoxaban: No published studies have investigated the periprocedural safety of continued use of edoxaban, nor the appropriate ATI period for this anticoagulant in the setting of orthopaedic surgery. The ACC recommends an ATI period of 48 hours before surgery in patients with normal renal function and 72 hours in patients with renal impairment2. The ASRA guidelines recommend a 20- to 28-hour interruption period before neuraxial procedures, and 40 to 70 hours for patients with renal impairment29.

Acetyl salicylic acid – Aspirin (ASA): Bleeding risk while taking ASA in the perioperative period has been extensively studied, but conflicting results have been reported4,5. In particular, several studies have demonstrated the safety of continuing ASA during elective hip and knee surgery4,5.

Recent guidelines recommend continuing ASA in patients at moderate to high risk of cardiovascular events and discontinuing ASA 7 to 10 days before surgery in patients at low risk of cardiovascular events, acknowledging that the discontinuation of ASA may carry an increased risk of thrombotic events in patients with strong cardiovascular risk factors5,34.

Surgery should not be postponed in patients receiving ASA as the low risk of bleeding does not justify the surgical delay7,35,36. The ASRA guidelines also recommend continuing ASA regardless of dosage or indication before neuraxial procedures, citing multiple studies demonstrating that ASA does not significantly increase the risk of spinal hematomas following neuraxial blocks29. Notwithstanding, there is a risk of bleeding if ASA is taken in combination with other thromboprophylactic medication, hence ASA may be withheld during inpatient stay unless indicated for unstable angina or recent/frequent transient ischemic attacks23.

Clopidogrel: The 2012 American College of Chest Physicians (ACCP) guidelines recommend stopping clopidogrel or prasugrel 5 days before surgery34. Similarly, the ASRA guidelines recommend discontinuing clopidogrel 5 days before neuraxial procedures. The recent Scottish Intercollegiate Guidelines Network (SIGN) recommend that surgery should not be delayed, and platelets should not be administered prophylactically, although marginally greater blood loss should be anticipated. This is also associated with an increased risk of spinal hematoma when regional anesthesia is employed23. Bridging is not required during temporary clopidogrel discontinuation in the perioperative setting, but ASA should be continued in patients on dual antiplatelet therapy (DAPT) after stent placement37.

The antiplatelet effect of clopidogrel can only be overcome with platelet transfusions, since clopidogrel irreversibly inhibits platelet function and there is no known antidote for this drug. Platelet concentrates may be administered if platelet dysfunction is documented in a patient who requires urgent surgery, suffers continued bleeding, or sustains an intracranial hemorrhage. Desmopressin (0.3 μg/kg) may also be administered in such patients11.

Prasugrel: No data on the safety of continuing prasugrel in the setting of orthopaedic surgery has been published. The AACP recommends stopping clopidogrel or prasugrel 5 days before cardiac surgery34, whereas the ASRA recommends discontinuing prasugrel 7 days before neuraxial block29. No available reversal agent for prasugrel exists.

Ticagrelor: No data exists regarding the continuation of ticagrelor in orthopaedic procedures. Platelet aggregation returns to normal within 5 days of discontinuation of ticagrelor38. Consequently, the ASRA guidelines recommend discontinuing ticagrelor 5 days before any procedure29.

No specific reversal agent exists. PB2452, a monoclonal antibody fragment that binds ticagrelor, is being developed as an antidote for patients requiring urgent surgery or experiencing life-threatening bleeding39,40.

Conclusion: Given the varying indications for antithrombotics, medication diversity and patient heterogeneity, defining the optimal strategy for patients on these medications who present with acute lower extremity trauma and require urgent surgery remains a challenging task. Periprocedural interruption and/or correction of anticoagulant therapy is often a complex risk-benefit intervention, requiring a thorough assessment of the patient’s bleeding and thrombotic risks. The need to reverse the effect of the anticoagulant or antiplatelet drug should be determined by the need to perform surgery urgently. If surgery cannot be delayed, reversal agents or other corrective measures should be administered. Ultimately, orthopaedic surgeons should always strive to manage these patients in collaboration with their colleagues in cardiology, anesthesia, and other medical specialties.


1.         Baron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med. 2013;368(22):2113-2124. doi:10.1056/NEJMra1206531

2.         Doherty JU, Gluckman TJ, Hucker WJ, et al. 2017 ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients With Nonvalvular Atrial Fibrillation: A Report of the American College of Cardiology Clinical Expert Consensus Document Task Force. J Am Coll Cardiol. 2017;69(7):871-898. doi:10.1016/j.jacc.2016.11.024

3.         American Heart Association. http://www.heart.org. Accessed December 2, 2021. https://www.heart.org/en/

4.         Barlow BT, Hannon MT, Waldron JE. Preoperative Management of Antithrombotics in Arthroplasty. J Am Acad Orthop Surg. 2019;27(23):878-886. doi:10.5435/JAAOS-D-17-00827

5.         Hornor MA, Duane TM, Ehlers AP, et al. American College of Surgeons’ Guidelines for the Perioperative Management of Antithrombotic Medication. J Am Coll Surg. 2018;227(5):521-536.e1. doi:10.1016/j.jamcollsurg.2018.08.183

6.         Vivas D, Roldán I, Ferrandis R, et al. Perioperative and Periprocedural Management of Antithrombotic Therapy: Consensus Document of SEC, SEDAR, SEACV, SECTCV, AEC, SECPRE, SEPD, SEGO, SEHH, SETH, SEMERGEN, SEMFYC, SEMG, SEMICYUC, SEMI, SEMES, SEPAR, SENEC, SEO, SEPA, SERVEI, SECOT and AEU. Rev Esp Cardiol (Engl Ed). 2018;71(7):553-564. doi:10.1016/j.rec.2018.01.029

7.         Columbo JA, Lambour AJ, Sundling RA, et al. A Meta-analysis of the Impact of Aspirin, Clopidogrel, and Dual Antiplatelet Therapy on Bleeding Complications in Noncardiac Surgery. Ann Surg. 2018;267(1):1-10. doi:10.1097/SLA.0000000000002279

8.         Riedel MD, Watkins IT, McCormick JR, Van Lancker HP. Anticoagulation Strategies for the Orthopaedic Surgeon: Reversal and Timelines. Arch Bone Jt Surg. 2020;8(3):457-460. doi:10.22038/abjs.2019.44803.2222

9.         Pean CA, Goch A, Christiano A, Konda S, Egol K. Current Practices Regarding Perioperative Management of Patients With Fracture on Antiplatelet Therapy: A Survey of Orthopedic Surgeons. Geriatr Orthop Surg Rehabil. 2015;6(4):289-294. doi:10.1177/2151458515605156

10.       Kozek-Langenecker SA, Ahmed AB, Afshari A, et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology: First update 2016. Eur J Anaesthesiol. 2017;34(6):332-395. doi:10.1097/EJA.0000000000000630

11.       Spahn DR, Bouillon B, Cerny V, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Crit Care. 2019;23(1):98. doi:10.1186/s13054-019-2347-3

12.       Yassa R, Khalfaoui MY, Hujazi I, Sevenoaks H, Dunkow P. Management of anticoagulation in hip fractures: A pragmatic approach. EFORT Open Rev. 2017;2(9):394-402. doi:10.1302/2058-5241.2.160083

13.       Niessner A, Tamargo J, Morais J, et al. Reversal strategies for non-vitamin K antagonist oral anticoagulants: a critical appraisal of available evidence and recommendations for clinical management-a joint position paper of the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy and European Society of Cardiology Working Group on Thrombosis. Eur Heart J. 2017;38(22):1710-1716. doi:10.1093/eurheartj/ehv676

14.       Viktil KK, Lehre I, Ranhoff AH, Molden E. Serum Concentrations and Elimination Rates of Direct-Acting Oral Anticoagulants (DOACs) in Older Hip Fracture Patients Hospitalized for Surgery: A Pilot Study. Drugs Aging. 2019;36(1):65-71. doi:10.1007/s40266-018-0609-4

15.       Frenkel Rutenberg T, Velkes S, Vitenberg M, et al. Morbidity and mortality after fragility hip fracture surgery in patients receiving vitamin K antagonists and direct oral anticoagulants. Thromb Res. 2018;166:106-112. doi:10.1016/j.thromres.2018.04.022

16.       Taranu R, Redclift C, Williams P, et al. Use of Anticoagulants Remains a Significant Threat to Timely Hip Fracture Surgery. Geriatr Orthop Surg Rehabil. 2018;9:2151459318764150. doi:10.1177/2151459318764150

17.       King K, Polischuk M, Lynch G, et al. Early Surgical Fixation for Hip Fractures in Patients Taking Direct Oral Anticoagulation: A Retrospective Cohort Study. Geriatr Orthop Surg Rehabil. 2020;11:2151459320944854. doi:10.1177/2151459320944854

18.       Bruckbauer M, Prexl O, Voelckel W, et al. Impact of Direct Oral Anticoagulants in Patients With Hip Fractures. J Orthop Trauma. 2019;33(1):e8-e13. doi:10.1097/BOT.0000000000001329

19.       Schuetze K, Eickhoff A, Dehner C, Gebhard F, Richter PH. Impact of oral anticoagulation on proximal femur fractures treated within 24 h – A retrospective chart review. Injury. 2019;50(11):2040-2044. doi:10.1016/j.injury.2019.09.011

20.       Gosch M, Jacobs M, Bail H, Grueninger S, Wicklein S. Outcome of older hip fracture patients on anticoagulation: a comparison of vitamin K-antagonists and Factor Xa inhibitors. Arch Orthop Trauma Surg. 2021;141(4):637-643. doi:10.1007/s00402-020-03547-8

21.       Morris JC, O’Connor MI. Anticoagulation Management in Geriatric Orthopedic Trauma Patients. Curr Geri Rep. 2020;9(4):288-295. doi:10.1007/s13670-020-00345-3

22.       Yoo MS, Zhu S, Jiang SF, et al. Association of Reversal of Anticoagulation Preoperatively on 30-Day Mortality and Outcomes for Hip Fracture Surgery. Am J Med. 2020;133(8):969-975.e2. doi:10.1016/j.amjmed.2020.01.002

23.       Ktistakis I, Giannoudis V, Giannoudis PV. Anticoagulation therapy and proximal femoral fracture treatment: An update. EFORT Open Rev. 2016;1(8):310-315. doi:10.1302/2058-5241.1.160034

24.       Tharmarajah P, Pusey J, Keeling D, Willett K. Efficacy of warfarin reversal in orthopedic trauma surgery patients. J Orthop Trauma. 2007;21(1):26-30. doi:10.1097/BOT.0b013e31802c4f3c

25.       Recommendations | Hip fracture: management | Guidance | NICE. Accessed December 2, 2021. https://www.nice.org.uk/guidance/cg124/chapter/Recommendations

26.       Gulati V, Newman S, Porter KJ, et al. Implications of anticoagulant and antiplatelet therapy in patients presenting with hip fractures: a current concepts review. Hip Int. 2018;28(3):227-233. doi:10.1177/1120700018759300

27.       Moores TS, Beaven A, Cattell AE, Baker C, Roberts PJ. Preoperative warfarin reversal for early hip fracture surgery. J Orthop Surg (Hong Kong). 2015;23(1):33-36. doi:10.1177/230949901502300108

28.       Wadhera RK, Russell CE, Piazza G. Cardiology patient page. Warfarin versus novel oral anticoagulants: how to choose? Circulation. 2014;130(22):e191-193. doi:10.1161/CIRCULATIONAHA.114.010426

29.       Horlocker TT, Vandermeuelen E, Kopp SL, Gogarten W, Leffert LR, Benzon HT. Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Fourth Edition). Reg Anesth Pain Med. 2018;43(3):263-309. doi:10.1097/AAP.0000000000000763

30.       Glund S, Stangier J, van Ryn J, et al. Effect of Age and Renal Function on Idarucizumab Pharmacokinetics and Idarucizumab-Mediated Reversal of Dabigatran Anticoagulant Activity in a Randomized, Double-Blind, Crossover Phase Ib Study. Clin Pharmacokinet. 2017;56(1):41-54. doi:10.1007/s40262-016-0417-0

31.       Eikelboom JW, Kozek-Langenecker S, Exadaktylos A, et al. Emergency care of patients receiving non-vitamin K antagonist oral anticoagulants. Br J Anaesth. 2018;120(4):645-656. doi:10.1016/j.bja.2017.11.082

32.       Kustos SA, Fasinu PS. Direct-Acting Oral Anticoagulants and Their Reversal Agents-An Update. Medicines (Basel). 2019;6(4):E103. doi:10.3390/medicines6040103

33.       Mujer MTP, Rai MP, Atti V, et al. An Update on the Reversal of Non-Vitamin K Antagonist Oral Anticoagulants. Adv Hematol. 2020;2020:7636104. doi:10.1155/2020/7636104

34.       Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e326S-e350S. doi:10.1378/chest.11-2298

35.       Keeling D, Tait RC, Watson H, British Committee of Standards for Haematology. Peri-operative management of anticoagulation and antiplatelet therapy. Br J Haematol. 2016;175(4):602-613. doi:10.1111/bjh.14344

36.       Kennedy MT, Roche S, Fleming SM, Lenehan B, Curtin W. The association between aspirin and blood loss in hip fracture patients. Acta Orthop Belg. 2006;72(1):29-33.

37.       Fleisher LA, Fleischmann KE, Auerbach AD, et al. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Developed in collaboration with the American College of Surgeons, American Society of Anesthesiologists, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Anesthesiologists, and Society of Vascular Medicine Endorsed by the Society of Hospital Medicine. J Nucl Cardiol. 2015;22(1):162-215. doi:10.1007/s12350-014-0025-z

38.       Gurbel PA, Bliden KP, Butler K, et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009;120(25):2577-2585. doi:10.1161/CIRCULATIONAHA.109.912550

39.       Bhatt DL, Pollack CV, Weitz JI, et al. Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers. N Engl J Med. 2019;380(19):1825-1833. doi:10.1056/NEJMoa1901778

40.       Nylander S, Pehrsson S, Inghardt T, et al. A specific antidote for ticagrelor. Journal of the American College of Cardiology. 2015;65(10_Supplement):A253-A253. doi:10.1016/S0735-1097(15)60253-4

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: