Alexander J. Acuña, Andy Kuo, Giedrius Kvederas, Atul F. Kamath.
Response/Recommendation: There is no concrete data related to this issue. However, because of a potential association between allogeneic blood transfusion and postoperative venous thromboembolism (VTE), we recommend that strategies be in place to reduce intraoperative blood loss and the possible need for allogeneic blood transfusion.
Recommendation: Limited.
Rationale: Despite contemporary advancements in blood conservation strategies, patients undergoing major orthopaedic surgery may experience significant intraoperative blood loss necessitating perioperative blood transfusions1–5. Notably, transfusion rates among modern cohorts undergoing complex total joint arthroplasty (TJA), spine surgery, or revision procedures may reach up to 20%6–13. Despite ongoing efforts to limit perioperative blood loss, it remains unclear whether the incidence of postoperative VTE is influenced by the volume of intraoperative blood loss or by the receipt of blood transfusion in the perioperative period.
While Goel et al., recently analyzed the National Surgical Quality Improvement Program (NSQIP) database and reported a significantly higher risk of VTE among orthopaedic surgery patients receiving perioperative blood transfuions10, analyses on separate cohorts undergoing specific surgical procedures including TJA14–23, spine surgery24–37, pediatric trauma surgery38, and surgery for lower extremity and pelvic fractures39–44 have demonstrated inconsistent results.
There is some evidence from retrospective studies of patients undergoing TJA that a higher volume of blood loss and transfusion requirements may be associated with a higher incidence of VTE15,19,21,22. Notably, in their analysis of 1’721,806 TJA patients, Parvizi et al., identified transfusion as an independent risk factor for postoperative VTE19. However, these findings remain mixed in orthopaedic literature14,16–18,20, with other studies failing to identify an association after controlling for various patient and surgical factors, such as VTE prophylaxis18 and postoperative hemoglobin levels14.
Two meta-analyses27,28 evaluating the relationship between blood loss and postoperative VTE in spine surgery have presented contradictory findings. While Xin et al., identified blood loss to be associated with VTE risk among patients undergoing spine surgery, the majority of included studies primarily conducted univariate analyses without adjusting for confounding factors28. Additionally, while Zhang et al., did not identify a relationship between intraoperative blood loss and VTE incidence, their pooled analysis did identify transfusion as a risk factor for VTE27. Similar to studies evaluating TJA, literature evaluating patients undergoing spine surgery have demonstrated inconsistent results when assessing both blood loss24–26,29–31 and transfusion24,29,30,37,45,46.
However, there is some evidence to suggest that the region of the spine being operated on may affect these relationships, with the majority of lumbar spine studies demonstrating a higher risk of VTE among transfused patients24,37,45,46. Although, Aoude et al., did not find an association between transfusion and VTE incidence among thoracic spinal fusion patients, perioperative blood transfusion was associated with a significantly higher risk of pulmonary embolism (PE) and overall VTE in their lumbar fusion cohort46.
Analyses evaluating the impact of perioperative blood loss and transfusion on VTE risk in patients with lower extremity and pelvic fractures have also demonstrated varying results. While patients suffering from postoperative VTE have been reported to have comparably higher blood loss40–42, it is unclear whether this independently affects the postoperative risk of VTE41,42. Additionally, there is mixed data regarding the relationship between perioperative blood transfusion and deep venous thrombosis (DVT)39,40,43,44. However, it is important to note that other studies utilizing multivariate analyses among patients without malignancy have demonstrated a higher risk of DVT among patients receiving transfusions39,40.
The inconsistencies demonstrated across included studies may be due to methodological limitations of the respective studies exploring this topic. Of note, a large proportion of studies failed to control for patient- and procedure-related VTE risk factors as well as variations in implemented VTE prophylaxis protocols. Similarly, variability in the use of tranexamic acid47–49 or tourniquets50 in certain procedures, as well as the accuracy of estimated blood loss51,52 may contribute to these inconsistent results. Furthermore, although blood transfusion represents a surrogate measure of perioperative blood loss, there is some evidence that red blood cell transfusion itself may induce a hypercoagulable state53–56.
Based on the available literature, there is insufficient evidence to definitively conclude that the incidence of VTE is associated with the volume of intraoperative blood loss or the receipt of perioperative blood transfusions. However, the implementation of perioperative strategies to reduce blood loss and transfusion rates remain essential given their historic relationship with other perioperative complications3,5.
References:
1. Roberts SB, Dhokia R, Tsirikos AI. Blood loss management in major elective orthopaedic surgery. Orthopaedics and Trauma. 2019;33(4):231-238. doi:10.1016/j.mporth.2019.05.005
2. Sambandam B, Batra S, Gupta R, Agrawal N. Blood conservation strategies in orthopedic surgeries: A review. Journal of Clinical Orthopaedics and Trauma. 2013;4(4):164-170. doi:10.1016/j.jcot.2013.11.002
3. Fafalak M, Cushner FD. Blood Loss in Orthopedic Surgery: A Historical Review. In: Techniques in Orthopaedics. Vol 32. Lippincott Williams and Wilkins; 2017:2-11. doi:10.1097/BTO.0000000000000203
4. Lu Q, Peng H, Zhou G, Yin D. Perioperative Blood Management Strategies for Total Knee Arthroplasty. Orthopaedic Surgery. 2018;10(1):8-16. doi:10.1111/os.12361
5. Ponnusamy KE, Kim TJ, Khanuja HS. Perioperative blood transfusions in orthopaedic surgery. Journal of Bone and Joint Surgery – American Volume. 2014;96(21):1836-1844. doi:10.2106/JBJS.N.00128
6. Menendez ME, Lu N, Huybrechts KF, et al. Variation in Use of Blood Transfusion in Primary Total Hip and Knee Arthroplasties. Journal of Arthroplasty. 2016;31(12):2757-2763.e2. doi:10.1016/j.arth.2016.05.022
7. Slover J, Lavery JA, Schwarzkopf R, Iorio R, Bosco J, Gold HT. Incidence and Risk Factors for Blood Transfusion in Total Joint Arthroplasty: Analysis of a Statewide Database. Journal of Arthroplasty. 2017;32(9):2684-2687.e1. doi:10.1016/j.arth.2017.04.048
8. Spahn DR. Anemia and Patient Blood Management in Hip and Knee Surgery. Anesthesiology. 2010;113(2):482-495. doi:10.1097/ALN.0b013e3181e08e97
9. Browne JA, Adib F, Brown TE, Novicoff WM. Transfusion rates are increasing following total hip arthroplasty: Risk factors and outcomes. Journal of Arthroplasty. 2013;28(8 SUPPL):34-37. doi:10.1016/j.arth.2013.03.035
10. Goel R, Patel EU, Cushing MM, et al. Association of perioperative red blood cell transfusions with venous thromboembolism in a North American Registry. JAMA Surgery. 2018;153(9):826-833. doi:10.1001/jamasurg.2018.1565
11. Sershon RA, Fillingham YA, Malkani AL, et al. Independent Risk Factors for Transfusion in Contemporary Revision Total Hip Arthroplasty. Journal of Arthroplasty. 2021;0(0). doi:10.1016/j.arth.2021.03.032
12. Fisahn C, Schmidt C, Schroeder JE, et al. Blood Transfusion and Postoperative Infection in Spine Surgery: A Systematic Review. Global Spine Journal. 2018;8(2):198-207. doi:10.1177/2192568217747572
13. Janssen SJ, Braun Y, Wood KB, Cha TD, Schwab JH. Allogeneic blood transfusions and postoperative infections after lumbar spine surgery. Spine Journal. 2015;15(5):901-909. doi:10.1016/j.spinee.2015.02.010
14. Pedersen AB, Mehnert F, Overgaard S, Johnsen SP. Allogeneic blood transfusion and prognosis following total hip replacement: A population-based follow up study. BMC Musculoskeletal Disorders. 2009;10. doi:10.1186/1471-2474-10-167
15. Jiang T, Song K, Yao Y, Pan P, Jiang Q. Perioperative allogenic blood transfusion increases the incidence of postoperative deep vein thrombosis in total knee and hip arthroplasty. Journal of Orthopaedic Surgery and Research. 2019;14(1):235. doi:10.1186/s13018-019-1270-2
16. Hart A, Khalil JA, Carli A, Huk O, Zukor D, Antoniou J. Blood transfusion in primary total hip and knee arthroplasty. Incidence, risk factors, and thirty-day complication rates. Journal of Bone and Joint Surgery – American Volume. 2014;96(23):1945-1951. doi:10.2106/JBJS.N.00077
17. Frisch NB, Wessell NM, Charters MA, Yu S, Jeffries JJ, Silverton CD. Predictors and complications of blood transfusion in total hip and knee arthroplasty. Journal of Arthroplasty. 2014;29(9 SUPPL.):189-192. doi:10.1016/j.arth.2014.03.048
18. Jackson A, Goswami K, Yayac M, et al. Association of Perioperative Red Blood Cell Transfusion with Symptomatic Venous Thromboembolism Following Total Hip and Knee Arthroplasty. The Journal of Arthroplasty. 2020;0(0). doi:10.1016/j.arth.2020.07.027
19. Parvizi J, Huang R, Rezapoor M, Bagheri B, Maltenfort MG. Individualized Risk Model for Venous Thromboembolism After Total Joint Arthroplasty. Journal of Arthroplasty. 2016;31(9):180-186. doi:10.1016/j.arth.2016.02.077
20. Kim Y-H, Kim VEM. Factors Leading to Low Incidence of Deep Vein Thrombosis After Cementless and Cemented Total Knee Arthroplasty. Clinical Orthopaedics and Related Research (1976-2007). 1991;273.
21. Acuña AJ, Grits D, Samuel LT, Emara AK, Kamath AF. Perioperative Blood Transfusions Are Associated with a Higher Incidence of Thromboembolic Events After TKA: An Analysis of 333,463 TKAs. Clin Orthop Related Res. 2021;479(3):589-600. doi:10.1097/CORR.0000000000001513
22. Miyagi J, Funabashi N, Suzuki M, et al. Predictive indicators of deep venous thrombosis and pulmonary arterial thromboembolism in 54 subjects after total knee arthroplasty using multislice computed tomography in logistic regression models. International Journal of Cardiology. 2007;119(1):90-94. doi:10.1016/j.ijcard.2006.07.056
23. Gangireddy C, Rectenwald JR, Upchurch GR, et al. Risk factors and clinical impact of postoperative symptomatic venous thromboembolism. Journal of Vascular Surgery. 2007;45(2). doi:10.1016/j.jvs.2006.10.034
24. Yang SD, Ding WY, Yang DL, et al. Prevalence and risk factors of deep vein thrombosis in patients undergoing lumbar interbody fusion surgery. Medicine (United States). 2015;94(48). doi:10.1097/MD.0000000000002205
25. Edwards CC, Lessing NL, Ford L, Edwards CC. Deep Vein Thrombosis After Complex Posterior Spine Surgery: Does Staged Surgery Make a Difference? Spine Deformity. 2018;6(2):141-147. doi:10.1016/j.jspd.2017.08.012
26. Pateder DB, Gonzales RA, Kebaish KM, et al. Pulmonary embolism after adult spinal deformity surgery. Spine. 2008;33(3):301-305. doi:10.1097/BRS.0b013e31816245e1
27. Zhang L, Cao H, Chen Y, Jiao G. Risk factors for venous thromboembolism following spinal surgery: A meta-analysis. Medicine. 2020;99(29):e20954. doi:10.1097/MD.0000000000020954
28. Xin WQ, Xin QQ, Ming HL, et al. Predictable Risk Factors of Spontaneous Venous Thromboembolism in Patients Undergoing Spine Surgery. World Neurosurgery. 2019;127:451-463. doi:10.1016/j.wneu.2019.04.126
29. Wang TY, Sakamoto JT, Nayar G, et al. Independent predictors of 30-day perioperative deep vein thrombosis in 1346 consecutive patients after spine surgery. World Neurosurgery. 2015;84(6):1605-1612. doi:10.1016/j.wneu.2015.07.008
30. Kim HJ, Kepler C, Cunningham M, Rawlins B, Boachie-Adjei O. Pulmonary embolism in spine surgery: A comparison of combined anterior/posterior approach versus posterior approach surgery. Spine. 2011;36(2):177-179. doi:10.1097/BRS.0b013e3181cb4717
31. Piper K, Algattas H, DeAndrea-Lazarus IA, et al. Risk factors associated with venous thromboembolism in patients undergoing spine surgery. Journal of Neurosurgery: Spine. 2017;26(1):90-96. doi:10.3171/2016.6.SPINE1656
32. Yoshioka K, Murakami H, Demura S, Kato S, Tsuchiya H. Prevalence and Risk Factors for Development of Venous Thromboembolism after Degenerative Spinal Surgery. Spine. 2015;40(5):E301-E306. doi:10.1097/BRS.0000000000000727
33. Ikeda T, Miyamoto H, Hashimoto K, Akagi M. Predictable factors of deep venous thrombosis in patients undergoing spine surgery. Journal of Orthopaedic Science. 2017;22(2):197-200. doi:10.1016/j.jos.2016.11.014
34. Takahashi H, Yokoyama Y, Iida Y, et al. Incidence of venous thromboembolism after spine surgery. Journal of Orthopaedic Science. 2012;17(2):114-117. doi:10.1007/s00776-011-0188-2
35. Inoue H, Watanabe H, Okami H, Kimura A, Takeshita K. The Rate of Venous Thromboembolism Before and After Spine Surgery as Determined with Indirect Multidetector CT. JBJS Open Access. 2018;3(3):e0015. doi:10.2106/jbjs.oa.18.00015
36. Tominaga H, Setoguchi T, Tanabe F, et al. Risk factors for venous thromboembolism after spine surgery. Medicine (United States). 2015;94(5):e466. doi:10.1097/MD.0000000000000466
37. Johnson DJ, Johnson CC, Cohen DB, Wetzler JA, Kebaish KM, Frank SM. Thrombotic and Infectious Morbidity Are Associated with Transfusion in Posterior Spine Fusion. HSS Journal. 2017;13(2):152-158. doi:10.1007/s11420-017-9545-9
38. Allen CJ, Murray CR, Meizoso JP, et al. Risk factors for venous thromboembolism after pediatric trauma. In: Journal of Pediatric Surgery. Vol 51. W.B. Saunders; 2016:168-171. doi:10.1016/j.jpedsurg.2015.10.033
39. Wu L, Cheng B. Perioperative red blood cell infusion and deep vein thrombosis in patients with femoral and pelvic fractures: a propensity score matching. Journal of Orthopaedic Surgery and Research. 2021;16(1):1-10. doi:10.1186/s13018-021-02510-6
40. Fu YH, Liu P, Xu X, et al. Deep vein thrombosis in the lower extremities after femoral neck fracture: A retrospective observational study. Journal of Orthopaedic Surgery. 2020;28(1). doi:10.1177/2309499019901172
41. Zhang BF, Wei X, Huang H, et al. Deep vein thrombosis in bilateral lower extremities after hip fracture: A retrospective study of 463 patients. Clinical Interventions in Aging. 2018;13:681-689. doi:10.2147/CIA.S161191
42. Feng L, Xu L, Yuan W, Xu Z, Feng Z, Zhang H. Preoperative anemia and total hospitalization time are the independent factors of preoperative deep venous thromboembolism in Chinese elderly undergoing hip surgery. BMC Anesthesiology. 2020;20(1):1-6. doi:10.1186/s12871-020-00983-2
43. Johnston P, Wynn-Jones H, Chakravarty D, Boyle A, Parker MJ. Is perioperative blood transfusion a risk factor for mortality or infection after hip fracture? Journal of Orthopaedic Trauma. 2006;20(10):675-679. doi:10.1097/01.bot.0000249435.25751.e8
44. Mioc ML, Prejbeanu R, Vermesan D, et al. Deep vein thrombosis following the treatment of lower limb pathologic bone fractures – A comparative study. BMC Musculoskeletal Disorders. 2018;19(1):1-5. doi:10.1186/s12891-018-2141-4
45. Sebastian AS, Currier BL, Kakar S, et al. Risk Factors for Venous Thromboembolism following Thoracolumbar Surgery: Analysis of 43,777 Patients from the American College of Surgeons National Surgical Quality Improvement Program 2005 to 2012. Global Spine Journal. 2016;6(8):738-743. doi:10.1055/s-0036-1579553
46. Aoude A, Nooh A, Fortin M, et al. Incidence, Predictors, and Postoperative Complications of Blood Transfusion in Thoracic and Lumbar Fusion Surgery: An Analysis of 13,695 Patients from the American College of Surgeons National Surgical Quality Improvement Program Database. Global Spine Journal. 2016;6(8):756-764. doi:10.1055/s-0036-1580736
47. Fillingham YA, Ramkumar DB, Jevsevar DS, et al. The Efficacy of Tranexamic Acid in Total Hip Arthroplasty: A Network Meta-analysis. Journal of Arthroplasty. 2018;33(10):3083-3089.e4. doi:10.1016/j.arth.2018.06.023
48. Styron JF, Klika AK, Szubski CR, Tolich D, Barsoum WK, Higuera CA. Relative efficacy of tranexamic acid and preoperative anemia treatment for reducing transfusions in total joint arthroplasty. Transfusion. 2017;57(3):622-629. doi:10.1111/trf.13955
49. Lin ZX, Woolf SK. Safety, efficacy, and cost-effectiveness of tranexamic acid in orthopedic surgery. Orthopedics. 2016;39(2):119-130. doi:10.3928/01477447-20160301-05
50. Ahmed I, Chawla A, Underwood M, et al. Time to reconsider the routine use of tourniquets in total knee arthroplasty surgery. The bone & joint journal. 2021;103-B(5):830-839. doi:10.1302/0301-620X.103B.BJJ-2020-1926.R1
51. Nowicki PD, Ndika A, Kemppainen J, et al. Measurement of Intraoperative Blood Loss in Pediatric Orthopaedic Patients: Evaluation of a New Method. JAAOS: Global Research and Reviews. 2018;2(5):e014. doi:10.5435/jaaosglobal-d-18-00014
52. Rothermel LD, Lipman JM. Estimation of blood loss is inaccurate and unreliable. Surgery (United States). 2016;160(4):946-953. doi:10.1016/j.surg.2016.06.006
53. Yu FTH, Armstrong JK, Tripette J, Meiselman HJ, Cloutier G. A local increase in red blood cell aggregation can trigger deep vein thrombosis: Evidence based on quantitative cellular ultrasound imaging. Journal of Thrombosis and Haemostasis. 2011;9(3):481-488. doi:10.1111/j.1538-7836.2010.04164.x
54. Litvinov RI, Weisel JW. Role of red blood cells in haemostasis and thrombosis. ISBT Science Series. 2017;12(1):176-183. doi:10.1111/voxs.12331
55. Silvain J, Abtan J, Kerneis M, et al. Impact of red blood cell transfusion on platelet aggregation and inflammatory response in anemic coronary and noncoronary patients: The TRANSFUSION-2 study (Impact of transfusion of red blood cell on platelet activation and aggregation studied with flow cytometry use and light transmission aggregometry). Journal of the American College of Cardiology. 2014;63(13):1289-1296. doi:10.1016/j.jacc.2013.11.029
56. Zallen G, Moore EE, Ciesla DJ, Brown M, Biffl WL, Silliman CC. Stored red blood cells selectively activate human neutrophils to release IL-8 and secretory PLA2. Shock. 2000;13(1):29-33. doi:10.1097/00024382-200013010-00006