Carlos Bracho, Marjan Wouthuyzen-Bakker, German Salazar, Estuardo Barragan, Mathias Salazar, Edwin Larco.

Response/Recommendation: Yes.  It is recommended to either hold anti-coagulation or change to a less aggressive anticoagulation agent in cases of wound-related problems such as persistent wound drainage, bleeding or hematoma formation.

Strength of Recommendation: Low.

Rationale: Wound-related problems in the postoperative period following orthopedic surgery can be a devastating complication leading to prolonged postoperative morbidity, lower patient-reported outcome scores, revision surgery, and higher overall health care costs^1,2.  Wound-related problems entail a variety of complications that can occur after orthopaedic procedures, and generally include persistent wound drainage, wound infections, bleeding/hematoma formation, and tissue breakdown/dehiscence.  The association between bleeding, persistent wound drainage, hematoma formation and the use of therapeutic anticoagulation has been well studied after knee and hip arthroplasty3–8.  A detailed description on the incidence of wound-related problems per type of VTE prophylaxis is described in the consensus question: “Does the risk of post-operative wound problems in patients undergoing orthopaedic procedures differ between various VTE prophylactic agents?”  Despite the clear association between wound-related problems and the use of certain anticoagulants, none of the reviewed studies described which strategy should be used when wound-related problems occur in patients treated with a certain type of VTE prophylaxis.

Despite the lack of direct evidence for a particular intervention, we recommend that patients who develop wound-related problems after orthopedic procedures undergo tighter dosing of their vitamin K antagonist regimen to reduce an elevated international normalized ratio (INR) to optimal range if supratherapeutic, or reduce the dosage of direct-oral anticoagulants (DOAC), or change the anticoagulation regimen to a less aggressive agent such as aspirin (ASA) or possibly switching to low-molecular-weight heparin (LMWH) if there is a strong indication to maintain more potent anticoagulation over ASA^7–9.  The choice between LMWH or ASA should depend on the indication in which the initial anticoagulant was prescribed (e.g., atrial fibrillation, mechanical heart valve, intracardiac devices, previous thromboembolic events, etc.).  If possible, ASA is preferred above LMWH, as LMWH has been shown to be associated with a higher rate of wound complications compared to ASA.  Kulshrestha et al., demonstrated, in a randomized controlled trial, that 7.9% of patients that underwent total knee arthroplasty and were treated with LMWH developed wound-related complications compared to only 1.0% in patients treated with ASA (p < 0.001)10.  In addition, it has been demonstrated that LMWH is independently associated with prolonged wound drainage after total joint arthroplasty5.  If the patient was not on an anticoagulant for other reasons than primary VTE prophylaxis, temporarily discontinuation of anticoagulation should be considered if wound-related problems occur.  Pitto et al., demonstrated in patients undergoing knee arthroplasty that mobile mechanical compression decreases the rate of hospital readmissions related to bleeding complications, wound infection, and symptomatic VTE¹¹.  In addition, when persistent wound drainage is noted, physiotherapy – specifically articular range of motion – should be temporarily limited.

Switching to a less aggressive anticoagulant appears safe in terms of VTE prevention (Table 1).  A meta-analysis performed by Matharu et al., indicate that ASA does not increase the risk of VTE compared to other anticoagulants¹².  This finding is confirmed in a later meta-analysis specifically comparing ASA with rivaroxaban¹³.  Moreover, wound-related problems are not identified as a risk factor to develop a VTE¹⁴, supporting the safety of changing to a less potent anticoagulant like ASA in this particular patient category.

Table 1.          Safety and Efficacy Outcomes of Anticoagulants Used in Othopaedic Surgery.

Anticoagulant Type	VTE Incidence	Incidence of Bleeding	Reference
Warfarin	21.5%	3.2%	15
Unfractionated heparin	23.0%	3.5%	16
Dalteparin	11.9%	1.5%	17
Enoxaparin	13.5%	1.7%	17
Fondaparinux	6.5%	2.7%	18
Aspirin	0.3%	0.5%	19

VTE=Venous thromboembolism.

References:

1.         Cancienne JM, Awowale JT, Camp CL, et al. Therapeutic postoperative anticoagulation is a risk factor for wound complications, infection, and revision after shoulder arthroplasty. J Shoulder Elbow Surg. 2020;29(7S):S67-S72. doi:10.1016/j.jse.2019.11.029

2.         Abudu A, Sivardeen K a. Z, Grimer RJ, Pynsent PB, Noy M. The outcome of perioperative wound infection after total hip and knee arthroplasty. Int Orthop. 2002;26(1):40-43. doi:10.1007/s00264-001-0301-9

3.         Parvizi J, Ghanem E, Joshi A, Sharkey PF, Hozack WJ, Rothman RH. Does “excessive” anticoagulation predispose to periprosthetic infection? J Arthroplasty. 2007;22(6 Suppl 2):24-28. doi:10.1016/j.arth.2007.03.007

4.         McDougall CJ, Gray HS, Simpson PM, Whitehouse SL, Crawford RW, Donnelly WJ. Complications related to therapeutic anticoagulation in total hip arthroplasty. J Arthroplasty. 2013;28(1):187-192. doi:10.1016/j.arth.2012.06.001

5.         Patel VP, Walsh M, Sehgal B, Preston C, DeWal H, Di Cesare PE. Factors associated with prolonged wound drainage after primary total hip and knee arthroplasty. J Bone Joint Surg Am. 2007;89(1):33-38. doi:10.2106/JBJS.F.00163

6.         Healy WL, Della Valle CJ, Iorio R, et al. Complications of total knee arthroplasty: standardized list and definitions of the Knee Society. Clin Orthop Relat Res. 2013;471(1):215-220. doi:10.1007/s11999-012-2489-y

7.         Jameson SS, Rymaszewska M, Hui ACW, James P, Serrano-Pedraza I, Muller SD. Wound complications following rivaroxaban administration: a multicenter comparison with low-molecular-weight heparins for thromboprophylaxis in lower limb arthroplasty. J Bone Joint Surg Am. 2012;94(17):1554-1558. doi:10.2106/JBJS.K.00521

8.         Gill SK, Theodorides A, Smith N, et al. Wound problems following hip arthroplasty before and after the introduction of a direct thrombin inhibitor for thromboprophylaxis. Hip Int. 2011;21(6):678-683. doi:10.5301/HIP.2011.8842

9.         Zou Y, Tian S, Wang Y, Sun K. Administering aspirin, rivaroxaban and low-molecular-weight heparin to prevent deep venous thrombosis after total knee arthroplasty. Blood Coagul Fibrinolysis. 2014;25(7):660-664. doi:10.1097/MBC.0000000000000121

10.       Kulshrestha V, Kumar S. DVT prophylaxis after TKA: routine anticoagulation vs risk screening approach – a randomized study. J Arthroplasty. 2013;28(10):1868-1873. doi:10.1016/j.arth.2013.05.025

11.       Pitto RP, Hamer H, Heiss-Dunlop W, Kuehle J. Mechanical prophylaxis of deep-vein thrombosis after total hip replacement a randomised clinical trial. J Bone Joint Surg Br. 2004;86(5):639-642. doi:10.1302/0301-620x.86b5.14763

12.       Matharu GS, Kunutsor SK, Judge A, Blom AW, Whitehouse MR. Clinical Effectiveness and Safety of Aspirin for Venous Thromboembolism Prophylaxis After Total Hip and Knee Replacement: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Intern Med. 2020;180(3):376-384. doi:10.1001/jamainternmed.2019.6108

13.       Xu J, Kanagaratnam A, Cao JY, Chaggar GS, Bruce W. A comparison of aspirin against rivaroxaban for venous thromboembolism prophylaxis after hip or knee arthroplasty: A meta-analysis. J Orthop Surg (Hong Kong). 2020;28(1):2309499019896024. doi:10.1177/2309499019896024

14.       Arcelus JI, Kudrna JC, Caprini JA. Venous thromboembolism following major orthopedic surgery: what is the risk after discharge? Orthopedics. 2006;29(6):506-516. doi:10.3928/01477447-20060601-16

15.       Anderson DR, Dunbar MJ, Bohm ER, et al. Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty: a randomized trial. Ann Intern Med. 2013;158(11):800-806. doi:10.7326/0003-4819-158-11-201306040-00004

16.       Mont MA, Jacobs JJ, Boggio LN, et al. Preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Am Acad Orthop Surg. 2011;19(12):768-776. doi:10.5435/00124635-201112000-00007

17.       Turpie AGG, Bauer KA, Eriksson BI, Lassen MR. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med. 2002;162(16):1833-1840. doi:10.1001/archinte.162.16.1833

18.       Freedman KB, Brookenthal KR, Fitzgerald RH, Williams S, Lonner JH. A meta-analysis of thromboembolic prophylaxis following elective total hip arthroplasty. J Bone Joint Surg Am. 2000;82-A(7):929-938. doi:10.2106/00004623-200007000-00004

19.       Raphael IJ, Tischler EH, Huang R, Rothman RH, Hozack WJ, Parvizi J. Aspirin: an alternative for pulmonary embolism prophylaxis after arthroplasty? Clin Orthop Relat Res. 2014;472(2):482-488. doi:10.1007/s11999-013-3135-z