91 – Does VTE prophylaxis in patients with chronic liver disease need to be altered when undergoing orthopaedic procedures?

91 – Does VTE prophylaxis in patients with chronic liver disease need to be altered when undergoing orthopaedic procedures?

Filippo Randelli, Emanuele Chisari, Viganò Martino, Claudio Cimminiello.

Response/Recommendation: Chronic liver disease (CLD) alone should not be considered a reason to withhold or alter venous thromboembolism (VTE) prophylaxis. The decision to possibly modify VTE prophylaxis should be multidisciplinary and individualized on individual CLD patients’ risk factors for both VTE and bleeding.

Strength of Recommendation: Consensus.

Rationale: CLD encompasses a broad spectrum of etiologies and ranging from viral diseases and alcohol abuse to hereditary and autoimmune disorders, altogether representing the fifth cause of mortality worldwide1.

CLD patients often present an associated coagulopathy with an increased international normalized ratio (INR). In the past, this acquired coagulopathy led the physicians to the false perception that such patients could be considered “self-anticoagulated”. The known reduction of anticoagulant factors is often balanced by an analog reduction of procoagulant ones.

In a prospective case-control study on hospitalized patients, Gulley et al., found that the rates VTE events were doubled in cirrhotic patients, 1.8% vs. 0.9%2. Smith et al., retrospectively reviewed 410 patients hospitalized with a diagnosis of cirrhosis, founding an overall incidence of VTE events of 0.7%3. In a nationwide cohort study conducted on the Danish population, Jepsen et al., found that the risk for VTE events in the cirrhotic outpatient population was almost doubled with respect to their healthy, matched controls. Moreover, it was also observed that cirrhotic patients, after a VTE, had an increased 90-days mortality4. An increased risk of deep venous thrombosis (DVT) in liver cirrhosis with respect to the general population was also described by Zhang et al., in a systematic review on the prevalence of venous thromboembolism in the Asian population5.

It has been widely recognized that CLD patients have poorer outcome in orthopaedic surgery with an increased risk of disseminated intravascular coagulation, infections, intra-operative bleeding, post-operative anemia requiring blood transfusions, 90-days readmission and hardware failure6-8.

Few studies analyzed VTE in CLD patients undergoing orthopaedic surgery. In several studies, DVT and pulmonary embolism (PE) are included in a broader category of “medical complications” and, even if these resulted as increase in CLD orthopaedic patients, it is not possible to assume a clear increased risk without extrapolated data7,9-14.

Nevertheless, the association between CLD and an increase in VTE in the orthopaedic population is not so straightforward, as some studies in literature report conflicting results12,15-17.

On the other hand, a robust body of works exists analyzing the question of VTE prophylaxis in the patients hospitalized with CLD. One major concern is its safety against bleeding. Literature does not support this concern18-21. The main independent risk factors for bleeding in CLD population were INR and platelets levels21.

There is low-quality evidence on safety profile of direct oral anticoagulants (DOAC) in CLD patients22-24. Recent guidelines25 recommend the preferential use of DOAC over low-molecular-weight heparin (LMWH) in the setting of VTE prophylaxis in orthopaedic surgery, but questions must be raised about such a recommendation in patients with liver disease who undergo orthopaedic surgery. Phase III studies with DOAC did not include subjects with severe liver disease/liver damage26.

Data regarding the efficacy of VTE prophylaxis in reducing VTE rates remain quite conflicting in this specific population. Barclay et al., reported a decreased incidence of VTE events in their cohorts treated with anticoagulants19,24, while other studies failed in retrieving the same results. In a systematic review on VTE prophylaxis in hospitalized patients with CLD, Wonjarupong et al., could not find any difference in thromboembolic events and bleeding events in patients with and without VTE prophylaxis27. In a retrospective analysis, also Moorehead et al., could not demonstrated an association between prophylaxis and a decrease in VTE risk28. Similar, not univocal results have also been reported by many other studies3,19,20.

Even tough not widely investigated throughout literature, CLD patients undergoing orthopaedic procedures not only are not protected by liver coagulopathy, but also show a possibly increased tendency toward VTE events. In this regard, given the acceptable safety of anticoagulants in this group of patients, CLD alone should not be considered a reason to withhold VTE prophylaxis, despite the conflicting results about its efficacy in the literature. The orthopaedic surgeon should anyway seek the advice of a multidisciplinary team of experts in an effort to maximize a thorough pre-operative evaluation and post-operative care. The use of risk scores like the Caprini Risk Assessment model29-33 can help in this population.


 1. Onochie E, Kayani B, Dawson-Bowling S, Millington S, Achan P, Hanna S. Total hip arthroplasty in patients with chronic liver disease: A systematic review. SICOT J. 2019;5:40. doi:10.1051/sicotj/2019037

2.   Gulley D, Teal E, Suvannasankha A, Chalasani N, Liangpunsakul S. Deep vein thrombosis and pulmonary embolism in cirrhosis patients. Dig Dis Sci. 2008;53(11):3012-3017. doi:10.1007/s10620-008-0265-3

3.   Smith CB, Hurdle AC, Kemp LO, Sands C, Twilla JD. Evaluation of venous thromboembolism prophylaxis in patients with chronic liver disease. J Hosp Med. 2013;8(10):569-573. doi:10.1002/jhm.2086

4.   Jepsen P, Tapper EB, Deleuran T, et al. Risk and outcome of venous and arterial thrombosis in patients with cirrhosis: a Danish nationwide cohort study [published online ahead of print, 2021 Jun 16]. Hepatology. 2021;10.1002/hep.32019. doi:10.1002/hep.32019

5.   Zhang Z, Shen B, Yang Lee LH, Gallus A, Jindal R, Wang C, Wu CC. Incidence of Venous Thromboembolism in Asian Populations: A Systematic Review. Thromb Haemost. 2017;117(12):2243-2260. doi:10.1160/TH17-02-0134

6.   Issa K, Boylan MR, Naziri Q, Perfetti DC, Maheshwari AV, Mont MA. The Impact of Hepatitis C on Short-Term Outcomes of Total Joint Arthroplasty. J Bone Joint Surg Am. 2015;97(23):1952-1957. doi:10.2106/JBJS.O.00183

7.   Sequeira SB, Labaran LA, Bell JE, Amin RM, Rao SS, Werner BC. Compensated Cirrhosis Is Associated With Increased Risk of Complications Following Total Hip Arthroplasty in a Large Medicare Database. J Arthroplasty. 2021;36(4):1361-1366.e1. doi:10.1016/j.arth.2020.10.008

8.   Bell JE, Amin R, Labaran LA, Sequeira SB, Rao SS, Werner BC. Impact of Compensated Cirrhosis Etiology on Postoperative Outcomes Following Total Knee Arthroplasty. J Arthroplasty. 2021;36(1):148-153.e1. doi:10.1016/j.arth.2020.07.019

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11. Best MJ, Buller LT, Klika AK, Barsoum WK. Increase in perioperative complications following primary total hip and knee arthroplasty in patients with hepatitis C without cirrhosis. J Arthroplasty. 2015;30(4):663-668. doi:10.1016/j.arth.2014.11.013

12. Rozell JC, Courtney PM, Dattilo JR, Wu CH, Lee GC. Late Complications Following Elective Primary Total Hip and Knee Arthroplasty: Who, When, and How?. J Arthroplasty. 2017;32(3):719-723. doi:10.1016/j.arth.2016.08.037

13. Lu Y, Lin CC, Stepanyan H, et al. Impact of Cirrhosis on Morbidity and Mortality After Spinal Fusion. Global Spine J. 2020;10(7):851-855. doi:10.1177/2192568219880823

14. Grau L, Zachwieja E, Summers SH, et al. Hepatitis C is an Independent Risk Factor for Perioperative Complications and Nonroutine Discharge in Patients Treated Surgically for Hip Fractures. J Orthop Trauma. 2018;32(11):565-572. doi:10.1097/BOT.0000000000001286

15. Deleuran T, Vilstrup H, Overgaard S, Jepsen P. Cirrhosis patients have increased risk of complications after hip or knee arthroplasty. Acta Orthop. 2015;86(1):108-113. doi:10.3109/17453674.2014.961397

16. Takahashi H, Yamamoto N, Nagamoto H, Sano H, Tanaka M, Itoi E. Venous thromboembolism after elective shoulder surgery: a prospective cohort study of 175 patients. J Shoulder Elbow Surg. 2014;23(5):605-612. doi:10.1016/j.jse.2014.01.054

17. Strotman PK, Schmitt DR, Schiff A, Pinzur M. Ankle fusion in patients with chronic hepatitis C. Foot Ankle Surg. 2020;26(2):151-155. doi:10.1016/j.fas.2019.01.001

18. Barclay SM, Jeffres MN, Nguyen K, Nguyen T. Evaluation of pharmacologic prophylaxis for venous thromboembolism in patients with chronic liver disease. Pharmacotherapy. 2013;33(4):375-382. doi:10.1002/phar.1218

19. Yerke J, Bauer SR, Bass S, et al. Effectiveness of venous thromboembolism prophylaxis in patients with liver disease. World J Hepatol. 2019;11(4):379-390. doi:10.4254/wjh.v11.i4.379

20. Intagliata NM, Henry ZH, Shah N, Lisman T, Caldwell SH, Northup PG. Prophylactic anticoagulation for venous thromboembolism in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding. Liver Int. 2014;34(1):26-32. doi:10.1111/liv.12211

21. Reichert JA, Hlavinka PF, Stolzfus JC. Risk of hemorrhage in patients with chronic liver disease and coagulopathy receiving pharmacologic venous thromboembolism prophylaxis. Pharmacotherapy. 2014;34(10):1043-1049. doi:10.1002/phar.1464

22. Intagliata NM, Henry ZH, Maitland H, et al. Direct Oral Anticoagulants in Cirrhosis Patients Pose Similar Risks of Bleeding When Compared to Traditional Anticoagulation. Dig Dis Sci. 2016;61(6):1721-1727. doi:10.1007/s10620-015-4012-25

23. Nisly SA, Mihm AE, Gillette C, Davis KA, Tillett J. Safety of direct oral anticoagulants in patients with mild to moderate cirrhosis: a systematic review and meta-analysis [published online ahead of print, 2021 Mar 16]. J Thromb Thrombolysis. 2021;10.1007/s11239-021-02424-4. doi:10.1007/s11239-021

24. K Steensig, M Pareek, A.L Krarup, P Sogaard, M Maeng, B Tayal, C Torp-Pedersen, G.Y.H Lip, P Holland-Fischer, K.H Kragholm, Reduced stroke risk without increased bleeding risk in patients with atrial fibrillation and complicated liver cirrhosis treated with oral anticoagulation, European Heart Journal, Volume 41, Issue Supplement_2, November 2020, ehaa946.0658,

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27. Wongjarupong, N; Laoveeravat, P; Udompap, P; Vantanasiri, K; Bakker, C. Venous Thromboembolism Prophylaxis in Hospitalized Patients With Chronic Liver Disease and the Bleeding and Thrombosis Risk: A Systematic Review and Meta-Analysis, The American Journal of Gastroenterology: October 2019 – Volume 114 – Issue – p S576-S577 doi: 10.14309/01.ajg.0000593504.66070.e5

28. Moorehead KJ, Jeffres MN, Mueller SW. A Retrospective Cohort Analysis of Pharmacologic VTE Prophylaxis and Padua Prediction Score in Hospitalized Patients With Chronic Liver Disease. J Pharm Pract. 2017;30(1):58-63. doi:10.1177/0897190015611570

29. Bogari H, Patanwala AE, Cosgrove R, Katz M. Risk-assessment and pharmacological prophylaxis of venous thromboembolism in hospitalized patients with chronic liver disease. Thromb Res. 2014;134(6):1220-1223. doi:10.1016/j.thromres.2014.09.031

30. Dauty M, Schmitt X, Menu P, Rousseau B, Dubois C. Using the Risk  Assessment and Predictor Tool (RAPT) for patients after total knee replacement surgery. Ann Phys Rehabil Med. 2012;55:4–15. doi: 10.1016/j.rehab.2011.10.006

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33 .Bateman  DK,  Dow  RW,  Brzezinski  A,  Bar-Eli  HY,  Kayiaros  ST. Correlation of the Caprini score and venous thromboembolism incidence  following  primary  total  joint  arthroplasty-results  of  a single-institution protocol. J Arthroplasty. 2017;32:3735–41. doi: 10.1016/j.arth.2017.06.042

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