Christiaan N. Mamczak, Josh Gary, Mark Walsh.
Response/Recommendation: Although previously validated in other surgical subspecialties to predict venous thromboembolism (VTE), thromboelastography (TEG) has not been adequately trialed within orthopaedic surgical care. However, studies suggest that TEG is a useful adjunct for assessing orthopaedic hypercoagulopathy and VTE after traumatic injury and/or surgical intervention based upon a maximal amplitude (MA) > 65 mm.
Strength of Recommendation: Moderate
Rationale: VTE prevention continues to be a high priority for orthopaedic surgeons. However, VTE is not always preventable despite administration of various chemical and/or mechanical prophylaxis measures, especially in the context of no universal gold standard protocol (i.e., specific medication and duration1–4).
Viscoelastic hemostatic assays (VHA), like TEG or rotational thromboelastometry (ROTEM), offer the most comprehensive method of assessing individual patient coagulopathy. VHA globally assess coagulopathy by providing a graphical representation of the entire clotting cascade from clot initiation through fibrinolysis. Serial TEG of the severe trauma patient demonstrates the transition from index hypocoagulability to postinjury or postsurgical hypercoagulability also validating VTE prevention5,6. Stutz et al., describe the value of VHA assessing the “safe zone” for anticoagulation where patients are neither undertreated and unprotected from VTE or overtreated and at risk for undesirable postoperative hemorrhage and/or wound complications7.
TEG has demonstrated mortality benefit over conventional coagulation tests (CCT: (activated partial thromboplastin time [aPTT] and prothrombin time [PT]/ international normalized ratio [INR]) when guiding initial blood product transfusion for the seriously injured polytrauma patient8. In tandem, orthopaedic literature on the use of VHA also surrounds trauma resuscitation and severe hemorrhage. Modified TEG with platelet mapping demonstrated a reduced ratio of fresh frozen plasma (1 unit) to packed red cells (2.5 units) and platelets (2.8 units) during massive transfusion of severe pelvic fractures9. In a different study, TEG reaction time (R-time) > 6 min was found to be an independent risk factor for death in patients with pelvic fractures (odds ratio [OR] 16; 95% confidence interval [CI] 5.4-53, p=0.0010) with no significant association with CCT10. Another retrospective review of perioperative transfusions during orthopaedic spine procedures, fracture and total joint arthroplasty (TJA) surgery found TEG-guided transfusion therapy reduced and optimized blood components (p<0.05) with improved coagulation function (p<0.05) and decreased hospital length of stay (p< 0.001) as compared to CCT. The risk of bleeding and thrombosis was not specifically studied11.
The progression towards a hypercoagulable state has been shown to occur early in the traumatic or postoperative phase. A prospective cohort polytrauma study found admission TEG hypercoagulability in 582/983 patients, with a doubled rate of deep venous thrombosis (DVT) despite prophylaxis when compared to hypocoagulable TEG patients (p=0.039)12. In a systematic review of 31 studies using TEG in orthopaedics, 17 studies cited MA as a significant predictor of VTE among a total of 6,348 patients13. Within this review, Brown et al., performed a selected meta-analysis of 5 studies with 3,180 patients to determine if an MA > 65 mm predicted VTE; they found an insignificant OR of 1.31 (95% CI, 0.74-2.34, p=0.175). Notably, the cutoff MA value to define hypercoagulability remains inconsistent within the literature and a limiting factor to its predictive value. However, this analysis found TEG consistently demonstrated hypercoagulability beginning soon after surgery. The study by Gary et al.14, and Cotton et al.15, were omitted from this meta-analysis despite being the initial studies indicating that an admission MA > 65 mm was a useful threshold for VTE prediction in orthopaedic trauma patients. In a retrospective cohort of 1,818 trauma patients stratified by extremity abbreviated injury severity scores ≥ 2 (ORTHO group) and <2 (non-ORTHO group), an admission MA > 65 mm constituted an OR of 3.66 for developing VTE, and MA > 72 mm increased the OR to 6.7014. In the prospective The Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial, there were early (< 12 days) and late (> 12 days) VTE events in trauma patients, with the preponderance of early events occurring within 72 hours of hospital admission and increased risk for patients with pelvic and/or femur fractures16.
Fibrinolytic shutdown, which describes the hypercoagulable state associated with the posttraumatic period, has been studied as a VTE prognosticator following orthopaedic trauma. Nelson et al., found fibrinolytic shutdown via TEG on initial assessment of pelvic fractures was not predictive of VTE17. The absence of correlation was not surprising in that the definition of fibrinolytic shutdown was only during the index presentation. It is more likely that prolonged shutdown over a series of hours or days (versus initial fibrinolysis shutdown) is a better predictor of thrombotic risk17,18. Future studies on serial VHA over a period of months following major orthopaedic trauma/surgery might validate the duration of VTE prophylaxis.
The value of serial TEG assays has demonstrated an improved understanding of coagulopathy during the perioperative phase. In a small study of 10 total knee arthroplasty (TKA), 10 total hip arthroplasty (THA) and 10 other lower extremity surgery controls, Okamura et al., found increased MA and coagulation index values 24-hours after TKA and THA surgery as compared to before anesthesia, indicating the early hypercoagulable state that can occur after TJA19. Kim et al., found intraoperative TEG tracings demonstrated increased hypercoagulable findings with decreased R-time and increased alpha angle and MA values (p<0.05) during a review of 45 elderly patients (age > 65) undergoing major orthopaedic surgery. These levels trended towards normal postoperatively when compared to preop TEG20. Finally, serial TEG found hypercoagulability in 250 patients with femoral neck fractures as measured in the preop, immediate postop, and 6-week postop timepoints, validating a correlation with the development of VTE21.
In general, there is a sparsity of orthopaedic literature on the routine use of TEG as an adjunctive test to direct perioperative care when compared to counterparts in other surgical subspecialties. VHA have expanded into more reproducible and less operator-dependent cartridge systems with rapid results. Future orthopaedic controlled trials are necessary to determine the effective role of VHA in predicting patient risk for VTE and their value in assessing the effectiveness and duration of VTE prophylaxis. Orthopaedic surgeons must become increasingly familiar with the tenants of VHA as they pertain to assessing the spectrum of coagulopathy and individualizing surgical care.
1. Rogers FB, Cipolle MD, Velmahos G, Rozycki G, Luchette FA. Practice management guidelines for the prevention of venous thromboembolism in trauma patients: the EAST practice management guidelines work group. J Trauma. 2002;53(1):142-164. doi:10.1097/00005373-200207000-00032
2. Morris RJ, Woodcock JP. Evidence-based compression: prevention of stasis and deep vein thrombosis. Ann Surg. 2004;239(2):162-171. doi:10.1097/01.sla.0000109149.77194.6c
3. Sagi HC, Ahn J, Ciesla D, et al. Venous Thromboembolism Prophylaxis in Orthopaedic Trauma Patients: A Survey of OTA Member Practice Patterns and OTA Expert Panel Recommendations. J Orthop Trauma. 2015;29(10):e355-362. doi:10.1097/BOT.0000000000000387
4. Parvizi J, Azzam K, Rothman RH. Deep venous thrombosis prophylaxis for total joint arthroplasty: American Academy of Orthopaedic Surgeons guidelines. J Arthroplasty. 2008;23(7 Suppl):2-5. doi:10.1016/j.arth.2008.06.028
5. Holley AD, Reade MC. The “procoagulopathy” of trauma: too much, too late? Curr Opin Crit Care. 2013;19(6):578-586. doi:10.1097/MCC.0000000000000032
6. Moore EE, Moore HB, Kornblith LZ, et al. Trauma-induced coagulopathy. Nat Rev Dis Primers. 2021;7(1):30. doi:10.1038/s41572-021-00264-3
7. Stutz CM, O’Rear LD, O’Neill KR, et al. Coagulopathies in orthopaedics: links to inflammation and the potential of individualizing treatment strategies. J Orthop Trauma. 2013;27(4):236-241. doi:10.1097/BOT.0b013e318269b782
8. Gonzalez E, Moore EE, Moore HB, et al. Goal-directed Hemostatic Resuscitation of Trauma-induced Coagulopathy: A Pragmatic Randomized Clinical Trial Comparing a Viscoelastic Assay to Conventional Coagulation Assays. Ann Surg. 2016;263(6):1051-1059. doi:10.1097/SLA.0000000000001608
9. Mamczak CN, Maloney M, Fritz B, et al. Thromboelastography in Orthopaedic Trauma Acute Pelvic Fracture Resuscitation: A Descriptive Pilot Study. J Orthop Trauma. 2016;30(6):299-305. doi:10.1097/BOT.0000000000000537
10. Kane I, Ong A, Orozco FR, Post ZD, Austin LS, Radcliff KE. Thromboelastography predictive of death in trauma patients. Orthop Surg. 2015;7(1):26-30. doi:10.1111/os.12158
11. Zhang Y, Song Y, Zhang Y, Yu L, Zhang K. Thromboelastogram-Guided Transfusion Therapy Reduces Blood-Component Transfusion and Improves Coagulation Function during Orthopedic Surgery. Journal of Nanomaterials. 2021;2021:e8218042. doi:10.1155/2021/8218042
12. Brill JB, Badiee J, Zander AL, et al. The rate of deep vein thrombosis doubles in trauma patients with hypercoagulable thromboelastography. J Trauma Acute Care Surg. 2017;83(3):413-419. doi:10.1097/TA.0000000000001618
13. Brown W, Lunati M, Maceroli M, et al. Ability of Thromboelastography to Detect Hypercoagulability: A Systematic Review and Meta-Analysis. J Orthop Trauma. 2020;34(6):278-286. doi:10.1097/BOT.0000000000001714
14. Gary JL, Schneider PS, Galpin M, et al. Can Thrombelastography Predict Venous Thromboembolic Events in Patients With Severe Extremity Trauma? J Orthop Trauma. 2016;30(6):294-298. doi:10.1097/BOT.0000000000000523
15. Cotton BA, Minei KM, Radwan ZA, et al. Admission rapid thrombelastography predicts development of pulmonary embolism in trauma patients. J Trauma Acute Care Surg. 2012;72(6):1470-1475; discussion 1475-1477. doi:10.1097/TA.0b013e31824d56ad
16. Myers SP, Brown JB, Leeper CM, et al. Early versus late venous thromboembolism: A secondary analysis of data from the PROPPR trial. Surgery. 2019;166(3):416-422. doi:10.1016/j.surg.2019.04.014
17. Nelson JT, Coleman JR, Carmichael H, et al. High Rate of Fibrinolytic Shutdown and Venous Thromboembolism in Patients With Severe Pelvic Fracture. J Surg Res. 2020;246:182-189. doi:10.1016/j.jss.2019.09.012
18. Meizoso JP, Karcutskie CA, Ray JJ, Namias N, Schulman CI, Proctor KG. Persistent Fibrinolysis Shutdown Is Associated with Increased Mortality in Severely Injured Trauma Patients. J Am Coll Surg. 2017;224(4):575-582. doi:10.1016/j.jamcollsurg.2016.12.018
19. Okamura K, Nakagawa I, Hidaka S, Okada Y, Kubo T, Kato T. [Perioperative changes of blood coagulability evaluated by thromboelastography (TEG) in patients undergoing total knee and total hip arthroplasty]. Masui. 2007;56(6):645-649.
20. Kim CJ, Ryu KH, Park SC, Lee J. Perioperative Changes in Thromboelastogram in Elderly Patients Receiving Major Orthopedic Surgery. Korean Journal of Anesthesiology. 2015;50(4):422-427.
21. Wilson D, Cooke EA, McNally MA, Wilson HK, Yeates A, Mollan RA. Changes in coagulability as measured by thrombelastography following surgery for proximal femoral fracture. Injury. 2001;32(10):765-770. doi:10.1016/s0020-1383(01)00139-5