Ayesha Abdeen, Maria Jurado, Jaime Mariño, Ernesto Guerra-Farfan.
Response/Recommendation: The incidence of readmission and re-operation for hematomas secondary to chemoprophylaxis for venous thromboembolism (VTE) in patients undergoing total joint arthroplasty (TJA) is low and not definitively related to the choice of anti-coagulant. There is a trend toward increased incidence of hematomas requiring re-operation in patients on enoxaparin in comparison to warfarin or factor Xa inhibitors. Thirty-day readmission rates are higher for all chemotherapeutic agents (low-molecular-weight heparin [LMWH], direct-oral anticoagulant [DOAC], warfarin), in comparison to aspirin (ASA). However, risk stratification practices resulting in higher-risk patients who have complex co-morbidities preferably receiving these more potent agents have not been eliminated as a confounding variable in existing studies.
Risk stratification can be done as per AAPS or ACCP guidelines with further information found in Question xxx.
Strength of Recommendation: Limited.
Rationale: The incidence of unplanned readmission following TJA has been reported to be 2.4 to 8.5% within 30 days and 5.3 to 11.9% at 90 days1–4.
Hematoma has been reported to be between the 3rd to 7th most common reason for readmission following primary TJA5,6 and accounts for up to 6.7% of readmissions following total hip arthroplasty (THA)6 and 8.5% of readmissions for total knee arthroplasty (TKA)2.
A variety of chemoprophylactic agents are used for VTE prevention following TJA including low- and high-dose ASA (81 mg or 325 mg, respectively), LMWH, warfarin, and newer DOAC such as factor Xa and thrombin inhibitors including rivaroxaban, apixaban, dabigatran. There is no universal consensus on the optimal strategy for risk stratification and choice of agent for VTE prevention following primary TJA. While DOAC have been demonstrated to be more effective and convenient for patients than injectable medications7, there remain concerns about increased risk of complications related to bleeding such as wound healing problems and hematomas, which can lead to unplanned readmissions and reoperations.
Multiple randomized control trials have shown that while both enoxaparin and warfarin have good efficacy for VTE prevention in TJA, enoxaparin is associated with a trend towards increased risks of major and minor bleeding. This finding was consistently a trend, but not always statistically significant8,9.
A meta-analysis comparing DOAC and LMWH for DVT prevention in TJA was performed using a dose-response model to evaluate the efficacy and safety of anticoagulation for the prevention of VTE in THA and TKA10. The therapeutic index was used to compare the safety and efficacy of a variety of chemoprophylactic agents. The therapeutic index-defined as a ratio of bleeding/efficacy using major bleeding (defined by the International Society on Thrombosis and Haemostasis) as the reference point for bleeding, and VTE as the reference point of efficacy, was found to be superior for factor Xa inhibitors (apixaban (5 mg/daily), rivaroxaban (10 mg daily), and edoxaban (30 mg daily) in comparison to both low- and high-dose LMWH (enoxaparin 40 mg daily or 30 mg twice a day [BID], respectively). Dabigatran was not found to be superior to enoxaparin for bleeding risk or efficacy. It was found that there is a difference in the efficacy and safety profile based upon regional variations of dosing of enoxaparin used: the 30 mg BID dosing (North American dosing) was associated with increased risk of major bleeding or clinically relevant bleeding compared to 40 mg once daily (European dosing)10.
Conversely, in a retrospective analysis of a prospective database11, use of factor Xa inhibitors was associated with a significantly higher rate of bleeding and wound complication in comparison to those on high-dose ASA in patients undergoing primary THA and TKA (18.7% vs. 0%, p < 0.03). Of the patients with bleeding and wound complications, however, only one developed a hematoma and two were readmitted. Another observational study assessed the incidence of post-operative complications in patients receiving either rivaroxaban or enoxaparin thromboprophylaxis for THA and TKA. There were no significant differences in the readmission rate between rivaroxaban and enoxaparin treated patients, nor in the incidence of minor bleeding (2.0% vs. 0%) and hemorrhagic wound complications (5.0% vs. 1.8%)12.
In a large single-center cohort of 17,784 patients undergoing TKA, the incidence of hematomas requiring re-operation within 30 days of surgery was 0.24%. Patients who had hematomas were compared to those who did not have hematomas (controls). A history of bleeding disorder (von Willebrand disease, or Hemophilia A, or B) was found to be associated with increased risk of hematomas requiring readmission and re-operation; pre-operative anticoagulation and type of post-operative anticoagulant (i.e., no chemoprophylaxis, ASA, LMWH, warfarin) were not found to be risk factors for hematoma formation13,14, although some studies revealed a higher rate of bleeding complications and reoperations following TKA using pre-operative warfarin management15 and pre-operative dalteparin16.
In a case-control series comparing patients who had TJA that developed periprosthetic joint infection (PJI) and controls who did not develop a PJI17, the authors found that patients who had international normalized ratio (INR) > 1.5 on warfarin chemoprophylaxis had an increased risk of PJI following TJA and patients who had PJI had higher rates of reoperation due to hematomas than those who had no infection, of whom the majority had an INR < 1.5.
In a retrospective review including 21,864 primary THA and TKA, it was found that 30-day readmission rates after primary THA were increased when the choice of VTE prophylaxis was any agent other than ASA. However, a major limitation of this study was that anticoagulant selection was mainly based on the discretion of the operative surgeon5.
As for revision TJA, it is thought that it may expose patients to higher VTE risks and for developing bleeding and infection complications. In a retrospective review of a database including 3,178 patients who underwent revision TJA19, administration of ASA to low-risk patients reached a higher efficacy than warfarin to reduce VTE events and reduced the incidence of reoperations for evacuation of post-operative hematomas. In a retrospective cohort study of 1,048 revision TJA19, when administering LMWH (tinzaparin) compared to DOAC (rivaroxaban), higher readmissions (9 vs. 22, p = 0.046) and reoperation rates (0 vs. 9, p = 0.032) were found.
Using a multimodal approach in which the treatment regimen is selected according to patient risk factors may be the best strategy. In a retrospective review of 1,179 consecutive TJA18, reoperations and readmissions due to wound hematomas occurred only in patients being managed with warfarin or LMWH (p = 0.0001), either for prophylaxis (high-risk factors) or for treatment of VTE/pulmonary embolism (PE), compared to those receiving antiplatelet chemoprophylaxis.
1. Workman KK, Angerett N, Lippe R, Shin A, King S. Thirty-Day Unplanned Readmission after Total Knee Arthroplasty at a Teaching Community Hospital: Rates, Reasons, and Risk Factors. J Knee Surg. 2020 Feb;33(02):206–12.
5. Ricciardi BF, Oi KK, Daines SB, Lee Y-Y, Joseph AD, Westrich GH. Patient and Perioperative Variables Affecting 30-Day Readmission for Surgical Complications After Hip and Knee Arthroplasties: A Matched Cohort Study. J Arthroplasty. 2017 Apr;32(4):1074–9.
6. Clement RC, Derman PB, Graham DS, Speck RM, Flynn DN, Levin LS, et al. Risk Factors, Causes, and the Economic Implications of Unplanned Readmissions Following Total Hip Arthroplasty. J Arthroplasty. 2013 Sep;28(8):7–10.
8. Fitzgerald RH, Spiro TE, Trowbridge AA, Gardiner GA, Whitsett TL, O’Connell MB, et al. Prevention of Venous Thromboembolic Disease Following Primary Total Knee Arthroplasty: A Randomized, Multicenter, Open-Label, Parallel-Group Comparison of Enoxaparin and Warfarin. J Bone Jt Surg-Am Vol. 2001 Jun;83(6):900–6.
9. Colwell CW, Collis DK, Paulson R, McCUTCHEN JW, Bigler GT, Lutz S, et al. Comparison of Enoxaparin and Warfarin for the Prevention of Venous Thromboembolic Disease After Total Hip Arthroplasty. Evaluation During Hospitalization and Three Months After Discharge*: J Bone Jt Surg. 1999 Jul;81(7):932–40.
10. Boyd R, DiCarlo L, Mandema J. Direct Oral Anticoagulants Vs. Enoxaparin for Prevention of Venous Thromboembolism Following Orthopedic Surgery: A Dose-Response Meta-analysis: Meta-analysis of DOACs for VTE Prevention. Clin Transl Sci. 2017 Jul;10(4):260–70.
11. Garfinkel JH, Gladnick BP, Roland N, Romness DW. Increased Incidence of Bleeding and Wound Complications With Factor-Xa Inhibitors After Total Joint Arthroplasty. J Arthroplasty. 2018 Feb;33(2):533–6.
12. Galat DD, McGovern SC, Hanssen AD, Larson DR, Harrington JR, Clarke HD. Early Return to Surgery for Evacuation of a Postoperative Hematoma After Primary Total Knee Arthroplasty: J Bone Jt Surg-Am Vol. 2008 Nov;90(11):2331–6.
13. Bern MM, Hazel D, Deeran E, Richmond JR, Ward DM, Spitz DJ, et al. Low dose compared to variable dose Warfarin and to Fondaparinux as prophylaxis for thromboembolism after elective hip or knee replacement surgery; a randomized, prospective study. Thromb J. 2015 Dec;13(1):32.
14. Jameson SS, Rymaszewska M, James P, Serrano-Pedraza I, Muller SD, Hui ACW, et al. Wound Complications Following Rivaroxaban Administration: A Multicenter Comparison with Low-Molecular-Weight Heparins for Thromboprophylaxis in Lower Limb Arthroplasty. J Bone Jt Surg. 2012 Sep 5;94(17):1554–8.
15. Gibon E, Barut N, Anract P, Courpied J-P, Hamadouche M. Ninety-Day Morbidity in Patients Undergoing Primary TKA With Discontinuation of Warfarin and Bridging With LMWH. J Arthroplasty. 2014 Jun;29(6):1185–8.
16. Hull RD. Low-Molecular-Weight Heparin Prophylaxis Using Dalteparin in Close Proximity to Surgery vs Warfarin in Hip Arthroplasty Patients: A Double-blind, Randomized Comparison. Arch Intern Med. 2000 Jul 24;160(14):2199.
18. Deirmengian GK, Heller S, Smith EB, Maltenfort M, Chen AF, Parvizi J. Aspirin Can Be Used as Prophylaxis for Prevention of Venous Thromboembolism After Revision Hip and Knee Arthroplasty. J Arthroplasty. 2016 Oct;31(10):2237–40.
19. Jensen CD, Steval A, Partington PF, Reed MR, Muller SD. Return to theatre following total hip and knee replacement, before and after the introduction of rivaroxaban: A RETROSPECTIVE COHORT STUDY. J Bone Joint Surg Br. 2011 Jan;93-B(1):91–5.
20. Dorr LD, Gendelman V, Maheshwari AV, Boutary M, Wan Z, Long WT. Multimodal Thromboprophylaxis for Total Hip and Knee Arthroplasty Based on Risk Assessment: J Bone Jt Surg-Am Vol. 2007 Dec;89(12):2648–57.