Leanne Ludwick, Ibrahim Tuncay.
Response/Recommendation: The most critical period for venous thromboembolism (VTE) development is within the first month after orthopaedic surgery, but the risk of VTE may persist for longer than expected.
Strength of Recommendation: Limited.
Rationale: The ideal duration of thromboprophylaxis after orthopaedic surgery is not clear and understanding the timeline of VTE episodes following orthopaedic procedures remains essential for optimizing VTE prophylaxis. Physicians must balance the efficacy of anticoagulation against its safety profile1. Limited data on the time course of VTE episodes following orthopaedic surgery exists. Of the available literature, the majority of studies focused on VTE following joint arthroplasty2–7 and spine8–11 procedures as these subspecialties are known to be associated with a higher risk of VTE.
Many studies have analyzed the timeline of VTE episodes following total joint arthroplasty (TJA) and other major joint procedures. It is well established that the risk of VTE continues long after discharge and approximately 50% to 75% of cases of VTE manifest post-discharge. In a retrospective database study, White et al., found that the median number of days to VTE following total knee arthroplasty (TKA) was 7 days, while the median following total hip arthroplasty (THA) was 14 days2. In their analysis of 19,586 THA and 24,059 TKA, 76% of the VTE diagnoses were after discharge for THA and 47% were after discharge for TKA. The findings of a retrospective study by Shohat et al., on the time to VTE following TKA were similar, with a median time to VTE of 8 days3.
Nevertheless, a prospective study by Dahl et al., found that the onset of deep venous thrombosis (DVT) symptoms occurred at an average of 17 days following TKA, 27 days following THA, and 36 days following hip fracture surgery4. Bjørnarå et al., reported similar timelines to Dahl et al., for TKA, THA, and hip fracture surgery, while also noting that symptomatic pulmonary embolism (PE) occurred earlier than DVT following TKA and hip fracture surgery. The median time to clinical VTE after hip fracture surgery was 24 days for DVT and 17 days for PE; for total hip revision (THR), this was 21 days and 34 days, respectively; for total knee revision (TKR), this was 20 days and 12 days, respectively6. Hu et al., focused on the timing of PE in patients following TJA and reported a median day of diagnosis of 3 days7. Parvizi et al., similarly found that 81% of events in patients on warfarin occurred within 3 days after TJA and 89% of events occurred within one week5.
While the reported numbers of days post-operation may vary, these studies demonstrate that the majority of VTE occurred after hospital discharge, but PE symptoms surfaced earlier compared to DVT. Plante et al., retrospectively investigated risk factors in 346 patients undergoing TKA and reported a mean time to VTE diagnosis of 5.6 days12. Campbell et al., evaluated the effectiveness of different prophylactic agents following hip fracture surgery in a large cohort13. In this study, most VTE events were seen in the first two weeks after surgery. However, despite different thromboprophylaxis methods, VTE continued to occur throughout the first 90 days. Arcelus et al., reported results of patients with VTE after major orthopaedic surgery in a multicenter, prospective study14. The mean time from surgery to VTE was 22 ± 16 days and the percentage of patients who developed VTE during the first 15 days after surgery was 47%. Fukuda et al., evaluated patients 5 days after TKA using an ultrasonography probe, detecting postoperative DVT in 81.3% and symptomatic PE in 1.7% of cases15. Senay et al.,16 aimed to assess the incidence of symptomatic VTE after discharge in patients who underwent TJA. They showed mean time from surgery to symptomatic VTE of 20.4 days (range, 5-84 days), while mean time from surgery to PE was 29.7 days (range, 9-84 days). Warwick et al., suggested a longer duration of prophylaxis in view of their results17. The mean times to VTE were 21.5 days for THA, and 9.7 days for TKA in that study. Kang et al., evaluated East Asian patients who underwent elective THA and reported that symptomatic DVT developed an average of 21 days (range, 10-47 days) after the operation18. In another observational study of 45,968 consecutive procedures, Lapidus et al., reported symptomatic VTE in orthopaedic surgery19. The median time to DVT was 16 days (range, 0–42 days) after surgery with 85% diagnosed after hospital discharge, whereas the median time to PE was 23 days (range,0–42 days) with 80% diagnosed after discharge.
Several studies also examined the time course to VTE in spine procedures. Cloney et al., studied the time to VTE following 6,869 cumulative spine surgeries in a single institution. The study showed that the rate of VTE increased linearly in the first two weeks following a spine procedure before reaching a plateau8. Li et al., performed a time-to-event analysis of VTE in patients undergoing spine surgery and identified a peak incidence in the first postoperative week11. More specifically, McClendon et al., analyzed the time to VTE in patients following spinal fusion greater than or equal to five levels9. They determined a mean time-to-event of 15 days following the operation. Additionally, the study by De le Garza Ramos et al., on the time course of postoperative complications following adult spinal deformity surgery reported a mean time to VTE of 12 days10. With similar time to VTE reported, these studies demonstrate that the majority of VTE events following spine procedures occur within the first two postoperative weeks.
While the time to diagnosis for PE may be earlier compared to the time to diagnosis for DVT, these studies suggest that the majority of VTE events following orthopaedic procedures occur after hospital discharge. By understanding the timeline of VTE events following orthopaedic procedures, physicians and patients can be made aware of critical high-risk periods that may focus efforts for mitigating VTE-related morbidity and mortality. Based on the current literature, the most critical period for VTE ranges from 3 to 27 days after orthopaedic surgery, but the risk for VTE may persist for longer than expected. It remains difficult to predict outcomes as the literature does not report homogenized results in terms of prophylaxis, diagnostic and treatment methods, as well as symptomatic and asymptomatic VTE.
References:
1. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e278S-e325S. doi:10.1378/chest.11-2404
2. White RH, Romano PS, Zhou H, Rodrigo J, Bargar W. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med. 1998;158(14):1525-1531. doi:10.1001/archinte.158.14.1525
3. Shohat N, Ludwick L, Goel R, Ledesma J, Streicher S, Parvizi J. Thirty Days of Aspirin for Venous Thromboembolism Prophylaxis Is Adequate Following Total Knee Arthroplasty, Regardless of the Dose Used. J Arthroplasty. Published online May 8, 2021:S0883-5403(21)00416-2. doi:10.1016/j.arth.2021.05.002
4. Dahl OE, Gudmundsen TE, Haukeland L. Late occurring clinical deep vein thrombosis in joint-operated patients. Acta Orthop Scand. 2000;71(1):47-50. doi:10.1080/00016470052943883
5. Parvizi J, Huang R, Raphael IJ, Maltenfort MG, Arnold WV, Rothman RH. Timing of Symptomatic Pulmonary Embolism with Warfarin Following Arthroplasty. J Arthroplasty. 2015;30(6):1050-1053. doi:10.1016/j.arth.2015.01.004
6. Bjørnarå BT, Gudmundsen TE, Dahl OE. Frequency and timing of clinical venous thromboembolism after major joint surgery. J Bone Joint Surg Br. 2006;88(3):386-391. doi:10.1302/0301-620X.88B3.17207
7. Hu C, Liu C, Wang Y, Ding T, Sun K, Tian S. The Timing of Symptomatic Pulmonary Embolism in Patients With Nonwarfarin Anticoagulants Following Elective Primary Total Joint Arthroplasty. J Arthroplasty. 2020;35(6):1703-1707. doi:10.1016/j.arth.2020.01.024
8. Cloney MB, Hopkins B, Dhillon ES, Dahdaleh NS. The timing of venous thromboembolic events after spine surgery: a single-center experience with 6869 consecutive patients. J Neurosurg Spine. 2018;28(1):88-95. doi:10.3171/2017.5.SPINE161399
9. McClendon J, Smith TR, O’Shaughnessy BA, Sugrue PA, Thompson SE, Koski TR. Time to Event Analysis for the Development of Venous Thromboembolism After Spinal Fusion ≥ 5 Levels. World Neurosurg. 2015;84(3):826-833. doi:10.1016/j.wneu.2015.03.068
10. De la Garza Ramos R, Goodwin CR, Passias PG, et al. Timing of Complications Occurring Within 30 Days After Adult Spinal Deformity Surgery. Spine Deform. 2017;5(2):145-150. doi:10.1016/j.jspd.2016.10.009
11. Li L, Li Z, Huo Y, Yang D, Ding W, Yang S. Time-to-event analyses of lower-limb venous thromboembolism in aged patients undergoing lumbar spine surgery: a retrospective study of 1620 patients. Aging (Albany NY). 2019;11(19):8701-8709. doi:10.18632/aging.102364
12. Plante S, Belzile EL, Fréchette D, Lefebvre J. Analysis of contributing factors influencing thromboembolic events after total knee arthroplasty. Can J Surg. 2017;60(1):30-36. doi:10.1503/cjs.008216
13. Campbell ST, Bala A, Jiang SY, Gardner MJ, Bishop JA. Are factor Xa inhibitors effective thromboprophylaxis following hip fracture surgery?: A large national database study. Injury. 2017;48(12):2768-2772. doi:10.1016/j.injury.2017.10.044
14. Arcelus JI, Monreal M, Caprini JA, et al. Clinical presentation and time-course of postoperative venous thromboembolism: Results from the RIETE Registry. Thromb Haemost. 2008;99(3):546-551. doi:10.1160/TH07-10-0611
15. Fukuda A, Hasegawa M, Kato K, Shi D, Sudo A, Uchida A. Effect of tourniquet application on deep vein thrombosis after total knee arthroplasty. Arch Orthop Trauma Surg. 2007;127(8):671-675. doi:10.1007/s00402-006-0244-0
16. Senay A, Trottier M, Delisle J, et al. Incidence of symptomatic venous thromboembolism in 2372 knee and hip replacement patients after discharge: data from a thromboprophylaxis registry in Montreal, Canada. Vasc Health Risk Manag. 2018;14:81-89. doi:10.2147/VHRM.S150474
17. Warwick D, Friedman RJ, Agnelli G, et al. Insufficient duration of venous thromboembolism prophylaxis after total hip or knee replacement when compared with the time course of thromboembolic events: findings from the Global Orthopaedic Registry. J Bone Joint Surg Br. 2007;89(6):799-807. doi:10.1302/0301-620X.89B6.18844
18. Kang BJ, Lee Y-K, Kim HJ, Ha Y-C, Koo K-H. Deep venous thrombosis and pulmonary embolism are uncommon in East Asian patients after total hip arthroplasty. Clin Orthop Relat Res. 2011;469(12):3423-3428. doi:10.1007/s11999-011-1979-7
19. Lapidus LJ, Ponzer S, Pettersson H, de Bri E. Symptomatic venous thromboembolism and mortality in orthopaedic surgery – an observational study of 45 968 consecutive procedures. BMC Musculoskelet Disord. 2013;14:177. doi:10.1186/1471-2474-14-177