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The role of D-dimer in periprosthetic joint infection: a systematic review and meta-analysis

  • Giovanni Balato , Cristiano De Franco , Fiamma Balboni ORCID logo EMAIL logo , Vincenzo De Matteo , Tiziana Ascione , Andrea Baldini and Giuseppe Lippi
Published/Copyright: May 19, 2021
Diagnosis
From the journal Diagnosis Volume 9 Issue 1

Abstract

Objectives

The current literature on diagnosis of periprosthetic joint infection (PJI) provides controversial evidence on the diagnostic accuracy of D-dimer. Therefore, this critical literature search and meta-analysis was aimed to summarize the diagnostic accuracy of D-dimer for diagnosing PJI.

Content

We searched MEDLINE, Scopus, and Web of Science, for studies on D-dimer for diagnosing PJI, according to the PRISMA flowchart. QUADAS was used for assessing study quality. Sensitivity, specificity, positive (PLR) and negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were analyzed using bivariate diagnostic random-effects model. The area under the receiver-operating curve (AUC-ROC) was calculated. Subgroup analysis and univariate meta-regression were carried out for detecting potential sources of heterogeneity.

Summary

We included 12 articles, totaling 1,818 patients (539 with PJI). The pooled sensitivity and specificity of D-dimer for diagnosing PJI were 0.739 (95% CI: 0.616–0.833) and 0.785 (95% CI: 0.679–0.863). The pooled PLR, NLR, DOR were 3.359 (95% CI, 2.340–4.821), 0.295 (95% CI, 0.180–0.484), and 11.787 (95% CI, 5.785–24.018). The cumulative ROC plot displayed an AUC of 0.688 (95% CI, 0.663–0.713; p<0.001). No threshold effects could be observed. The type of blood sample was identified as possible source of heterogeneity for DOR (p=0.01).

Outlook

Evidence emerged from this meta-analysis suggests that D-dimer displays sufficient diagnostic accuracy to rule out PJI. The type of blood sample (plasma vs. serum) and the study design could influence the results in terms of DOR and sensitivity. However, further perspective studies would be needed to validate its potential diagnostic usefulness.

Keywords: arthroplasty; D-dimer; diagnosis; periprosthetic joint infection
Corresponding author: Dr. Fiamma Balboni, Laboratory Service, Istituto Fiorentino Cura e Assistenza IFCA Florence, Florence, Italy, Phone: +39 0554296368, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Ethical approval: Not applicable.

References

1. Kurtz, SM, Ong, KL, Lau, E, Bozic, KJ, Berry, D, Parvizi, J. Prosthetic joint infection risk after TKA in the Medicare population. Clin Orthop Relat Res 2010;468:52–6. https://doi.org/10.1007/s11999-009-1013-5.Search in Google Scholar PubMed PubMed Central

2. Balato, G, Ascione, T, De Franco, C, De Matteo, V, Verrazzo, R, Smeraglia, F, et al.. Blood loss and transfusion rate in patients undergoing two-stage exchange in infected total knee arthroplasty. J Biol Regul Homeost Agents 2020;34:1–5.Search in Google Scholar

3. Gehrke, T, Alijanipour, P, Parvizi, J. The management of an infected total knee arthroplasty. Bone Joint J 2015;97-B:20–9. https://doi.org/10.1302/0301-620X.97B10.36475.Search in Google Scholar PubMed

4. Balato, G, Ascione, T, Rosa, D, Pagliano, P, Solarino, G, Moretti, B, et al.. Release of gentamicin from cement spacers in two-stage procedures for hip and knee prosthetic infection: an in vivo pharmacokinetic study with clinical follow-up. J Biol Regul Homeost Agents 2015;29:63–72.Search in Google Scholar

5. Ascione, T, Balato, G, Mariconda, M, Rotondo, R, Baldini, A, Pagliano, P. Continuous antibiotic therapy can reduce recurrence of prosthetic joint infection in patients undergoing 2-stage exchange. J Arthroplasty 2019;34:704–9. https://doi.org/10.1016/j.arth.2018.12.017.Search in Google Scholar PubMed

6. Parvizi, J, Tan, TL, Goswami, K, Higuera, C, Della Valle, C, Chen, AF, et al.. The 2018 definition of periprosthetic hip and knee infection: an evidence-based and validated criteria. J Arthroplasty 2018;33:1309–14.e2. https://doi.org/10.1016/j.arth.2018.02.078.Search in Google Scholar PubMed

7. Carli, AV, Abdelbary, H, Ahmadzai, N, Cheng, W, Shea, B, Hutton, B, et al.. Diagnostic accuracy of serum, synovial, and tissue testing for chronic periprosthetic joint infection after hip and knee replacements: a systematic review. J Bone Jt Surg Am 2019;101:635–49. https://doi.org/10.2106/JBJS.18.00632.Search in Google Scholar PubMed

8. Favresse, J, Lippi, G, Roy, P-M, Chatelain, B, Jacqmin, H, Ten Cate, H, et al.. D-dimer: preanalytical, analytical, postanalytical variables, and clinical applications. Crit Rev Clin Lab Sci 2018;55:548–77. https://doi.org/10.1080/10408363.2018.1529734.Search in Google Scholar PubMed

9. Shahi, A, Kheir, MM, Tarabichi, M, Hosseinzadeh, HRS, Tan, TL, Parvizi, J. Serum D-dimer test is promising for the diagnosis of periprosthetic joint infection and timing of reimplantation. J Bone Jt Surg Am 2017;99:1419–27. https://doi.org/10.2106/JBJS.16.01395.Search in Google Scholar PubMed

10. Lu, G, Li, T, Ye, H, Liu, S, Zhang, P, Wang, W. D-dimer in the diagnosis of periprosthetic joint infection: a systematic review and meta-analysis. J Orthop Surg Res 2020;15:265. https://doi.org/10.1186/s13018-020-01761-z.Search in Google Scholar PubMed PubMed Central

11. Zhang, H, Sun, X, Xin, P, Zhu, X, Jie, K, Cao, H, et al.. Diagnostic accuracy of D-dimer in periprosthetic joint infection: a diagnostic meta-analysis. J Orthop Surg Res 2020;15:334. https://doi.org/10.1186/s13018-020-01853-w.Search in Google Scholar PubMed PubMed Central

12. Li, C, Margaryan, D, Ojeda-Thies, C, Perka, C, Trampuz, A. Meta-analysis of serum and/or plasma D-dimer in the diagnosis of periprosthetic joint infection. J Orthop Surg Res 2020;15:298. https://doi.org/10.1186/s13018-020-01808-1.Search in Google Scholar PubMed PubMed Central

13. Wang, Y, Man, Z, Yuan, T, Cao, H, Sun, S. Reliability of d-dimer determination in diagnosis of peri-prosthetic joint infection: a systematic review and meta-analysis. Surg Infect 2021;22:374–82. https://doi.org/10.1089/sur.2020.212.Search in Google Scholar PubMed

14. Yan, J, Xie, K, Jiang, X, Han, X, Wang, L, Yan, M. D-dimer for diagnosis of periprosthetic joint infection: a meta-analysis. J Orthop Sci 2020. https://doi.org/10.1016/j.jos.2020.09.015.Search in Google Scholar PubMed

15. Zhang, Q, Dong, J, Zhou, D, Liu, F. Circulating D-dimer versus fibrinogen in the diagnosis of peri-prosthetic joint infection: a meta-analysis. Surg Infect 2021;22:200–10. https://doi.org/10.1089/sur.2019.298.Search in Google Scholar PubMed

16. Liberati, A, Altman, DG, Tetzlaff, J, Mulrow, C, Gøtzsche, PC, Ioannidis, JPA, et al.. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009;62:e1–34. https://doi.org/10.1016/j.jclinepi.2009.06.006.Search in Google Scholar PubMed

17. Whiting, PF, Rutjes, AWS, Westwood, ME, Mallett, S, Deeks, JJ, Reitsma, JB, et al.. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011;155:529–36. https://doi.org/10.7326/0003-4819-155-8-201110180-00009.Search in Google Scholar PubMed

18. Reitsma, JB, Glas, AS, Rutjes, AWS, Scholten, RJPM, Bossuyt, PM, Zwinderman, AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol 2005;58:982–90. https://doi.org/10.1016/j.jclinepi.2005.02.022.Search in Google Scholar PubMed

19. Shamseer, L, Moher, D, Clarke, M, Ghersi, D, Liberati, A, Petticrew, M, et al.. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015;350:g7647. https://doi.org/10.1136/bmj.g7647.Search in Google Scholar PubMed

20. Fu, J, Ni, M, Chai, W, Li, X, Hao, L, Chen, J. Synovial fluid viscosity test is promising for the diagnosis of periprosthetic joint infection. J Arthroplasty 2019;34:1197–200. https://doi.org/10.1016/j.arth.2019.02.009.Search in Google Scholar PubMed

21. Hu, Q, Fu, Y, Tang, L. Serum D-dimer as a diagnostic index of PJI and retrospective analysis of etiology in patients with PJI. Clin Chim Acta 2020;506:67–71. https://doi.org/10.1016/j.cca.2020.03.023.Search in Google Scholar PubMed

22. Huang, J, Zhang, Y, Wang, Z, Dong, Y, Zhao, Y, Zheng, J, et al.. The serum level of D-Dimer is not suitable for distinguishing between prosthetic joint infection and aseptic loosening. J Orthop Surg Res 2019;14:407. https://doi.org/10.1186/s13018-019-1461-x.Search in Google Scholar PubMed PubMed Central

23. Li, R, Shao, H-Y, Hao, L-B, Yu, B-Z, Qu, P-F, Zhou, Y-X, et al.. Plasma fibrinogen exhibits better performance than plasma D-dimer in the diagnosis of periprosthetic joint infection: a multicenter retrospective study. J Bone Jt Surg Am 2019;101:613–9. https://doi.org/10.2106/JBJS.18.00624.Search in Google Scholar PubMed

24. Qin, L, Li, F, Gong, X, Wang, J, Huang, W, Hu, N. Combined measurement of D-dimer and C-reactive protein levels: highly accurate for diagnosing chronic periprosthetic joint infection. J Arthroplasty 2020;35:229–34. https://doi.org/10.1016/j.arth.2019.08.012.Search in Google Scholar PubMed

25. Pannu, TS, Villa, JM, Patel, PD, Riesgo, AM, Barsoum, WK, Higuera, CA. The utility of serum d-dimer for the diagnosis of periprosthetic joint infection in revision total hip and knee arthroplasty. J Arthroplasty 2020;35:1692–5. https://doi.org/10.1016/j.arth.2020.01.034.Search in Google Scholar PubMed

26. Xiong, L, Li, S, Dai, M. Comparison of D-dimer with CRP and ESR for diagnosis of periprosthetic joint infection. J Orthop Surg Res 2019;14:240. https://doi.org/10.1186/s13018-019-1282-y.Search in Google Scholar PubMed PubMed Central

27. Xu, H, Xie, J, Huang, Q, Lei, Y, Zhang, S, Pei, F. Plasma fibrin degradation product and D-dimer are of limited value for diagnosing periprosthetic joint infection. J Arthroplasty 2019;34:2454–60. https://doi.org/10.1016/j.arth.2019.05.009.Search in Google Scholar PubMed

28. Ackmann, T, Möllenbeck, B, Gosheger, G, Schwarze, J, Schmidt-Braekling, T, Schneider, KN, et al.. Comparing the diagnostic value of serum D-dimer to CRP and IL-6 in the diagnosis of chronic prosthetic joint infection. J Clin Med 2020;9. https://doi.org/10.3390/jcm9092917.Search in Google Scholar PubMed PubMed Central

29. Wang, Y, Li, Y, Qiao, L, Sun, S. Comparison of a comprehensive set of fibrinolytic markers with C-reactive protein and erythrocyte sedimentation rate for the diagnosis of periprosthetic joint infection. J Arthroplasty 2020;35:2613–8. https://doi.org/10.1016/j.arth.2020.04.096.Search in Google Scholar PubMed

30. Grzelecki, D, Walczak, P, Grajek, A, Szostek, M, Dudek, P, Bartosz, P, et al.. Elevated plasma D-dimer concentration has higher efficacy for the diagnosis of periprosthetic joint infection of the knee than of the hip-A single-center, retrospective study. J Orthop Res 2021;39:291–8. https://doi.org/10.1002/jor.24897.Search in Google Scholar PubMed

31. Thachil, J, Lippi, G, Favaloro, EJ. D-dimer testing: laboratory aspects and current issues. Methods Mol Biol 2017;1646:91–104. https://doi.org/10.1007/978-1-4939-7196-1_7.Search in Google Scholar PubMed

32. Lippi, G, Franchini, M, Targher, G, Favaloro, EJ. Help me, Doctor! My D-dimer is raised. Ann Med 2008;40:594–605. https://doi.org/10.1080/07853890802161015.Search in Google Scholar PubMed

33. Lippi, G, Favaloro, EJ. D-dimer measurement in COVID-19: silver bullet or clinical distraction? Thromb Res 2020;196:635–7. https://doi.org/10.1016/j.thromres.2020.09.040.Search in Google Scholar PubMed PubMed Central

34. Pieper, CF, Rao, KM, Currie, MS, Harris, TB, Cohen, HJ. Age, functional status, and racial differences in plasma D-dimer levels in community-dwelling elderly persons. J Gerontol Biol Med Sci 2000;55:M649–57. https://doi.org/10.1093/gerona/55.11.m649.Search in Google Scholar PubMed

35. Zakai, NA, McClure, LA, Judd, SE, Kissela, B, Howard, G, Safford, M, et al.. D-dimer and the risk of stroke and coronary heart disease. The REasons for geographic and racial differences in stroke (REGARDS) study. Thromb Haemostasis 2017;117:618–24. https://doi.org/10.1160/TH16-07-0519.Search in Google Scholar PubMed PubMed Central

36. Nybo, M, Hvas, A-M. Age-adjusted D-dimer cut-off in the diagnostic strategy for deep vein thrombosis: a systematic review. Scand J Clin Lab Invest 2017;77:568–73. https://doi.org/10.1080/00365513.2017.1390783.Search in Google Scholar PubMed

37. Xie, J, Ma, J, Yao, H, Yue, C, Pei, F. Multiple boluses of intravenous tranexamic acid to reduce hidden blood loss after primary total knee arthroplasty without tourniquet: a randomized clinical trial. J Arthroplasty 2016;31:2458–64. https://doi.org/10.1016/j.arth.2016.04.034.Search in Google Scholar PubMed

38. Franchini, M, Liumbruno, GM, Bonfanti, C, Lippi, G. The evolution of anticoagulant therapy. Blood Transfus 2016;14:175–84. https://doi.org/10.2450/2015.0096-15.Search in Google Scholar PubMed PubMed Central

39. Bogut, A, Niedźwiadek, J, Strzelec-Nowak, D, Plewik, D, Mazurkiewicz, T, Marczyński, W, et al.. Characterization of Staphylococcus Epidermidis isolates cultured from patients with infected hip prostheses. Health Probl Civiliz 2018;12:132–8. https://doi.org/10.5114/hpc.2018.75491.Search in Google Scholar

40. Balato, G, de Matteo, V, Ascione, T, Di Donato, SL, De Franco, C, Smeraglia, F, et al.. Laboratory-based versus qualitative assessment of α-defensin in periprosthetic hip and knee infections: a systematic review and meta-analysis. Arch Orthop Trauma Surg 2020;140:293–301. https://doi.org/10.1007/s00402-019-03232-5.Search in Google Scholar PubMed

41. Longstaff, C, Adcock, D, Olson, JD, Jennings, I, Kitchen, S, Mutch, N, et al.. Harmonisation of D-dimer - a call for action. Thromb Res 2016;137:219–20.10.1016/j.thromres.2015.11.031Search in Google Scholar PubMed

42. Lippi, G, Tripodi, A, Simundic, AM, Favaloro, EJ. International survey on D-dimer test reporting: a call for standardization. Semin Thromb Hemost 2015;41:287–93.10.1055/s-0035-1549092Search in Google Scholar PubMed

43. Korte, W, Riesen, W. Latex-enhanced immunoturbidimetry allows D-dimer determination in plasma and serum samples. Clin Chem 2000;46:871–2.10.1093/clinchem/46.6.871Search in Google Scholar

44. Lippi, G, Favaloro, EJ. D-dimer measurement and laboratory feedback. J Emerg Med 2009;37:82–3. https://doi.org/10.1016/j.jemermed.2008.07.033.Search in Google Scholar PubMed

45. Boisclair, MD, Lane, DA, Wilde, JT, Ireland, H, Preston, FE, Ofosu, FA. A comparative evaluation of assays for markers of activated coagulation and/or fibrinolysis: thrombin-antithrombin complex, D-dimer and fibrinogen/fibrin fragment E antigen. Br J Haematol 1990;74:471–9. https://doi.org/10.1111/j.1365-2141.1990.tb06337.x.Search in Google Scholar PubMed

46. Korte, W, Riesen, WF. Comparability of serum and plasma concentrations of haemostasis activation markers. Clin Chem Lab Med 2001;39:627–30. https://doi.org/10.1515/CCLM.2001.101.Search in Google Scholar PubMed

Received: 2021-03-08
Accepted: 2021-04-19
Published Online: 2021-05-19

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. From Camille Nούς to Apollonian and the Dionysian scientists
  4. Review
  5. The role of D-dimer in periprosthetic joint infection: a systematic review and meta-analysis
  6. Mini Reviews
  7. Updated picture of SARS-CoV-2 variants and mutations
  8. Systematic review and cumulative meta-analysis of the diagnostic accuracy of glial fibrillary acidic protein vs. S100 calcium binding protein B as blood biomarkers in observational studies of patients with mild or moderate acute traumatic brain injury
  9. Opinion Papers
  10. The 6C model for accurately capturing the patient’s medical history
  11. Webside manner: maskless communication
  12. Original Articles
  13. Ways that nurse practitioner students self-explain during diagnostic reasoning
  14. Diagnostic reasoning: relationships among expertise, accuracy, and ways that nurse practitioner students self-explain
  15. Perspectives on the current state of pre-clerkship clinical reasoning instruction in United States medical schools: a survey of clinical skills course directors
  16. Use of a structured approach and virtual simulation practice to improve diagnostic reasoning
  17. Analyzing diagnostic errors in the acute setting: a process-driven approach
  18. Morning report goes virtual: learner experiences in a virtual, case-based diagnostic reasoning conference
  19. Stroke hospitalization after misdiagnosis of “benign dizziness” is lower in specialty care than general practice: a population-based cohort analysis of missed stroke using SPADE methods
  20. Discrepancy between emergency department admission diagnosis and hospital discharge diagnosis and its impact on length of stay, up-triage to the intensive care unit, and mortality
  21. Automated capture-based NGS workflow: one thousand patients experience in a clinical routine framework
  22. Short Communication
  23. Characterizing the relationship between diagnostic intensity and quality of care
  24. Case Reports – Lessons in Clinical Reasoning
  25. Lessons in clinical reasoning ‒ pitfalls, myths, and pearls: a case of confusion, disequilibrium, and “picking at the air”
  26. Hickam’s dictum, Occam’s razor, and Crabtree’s bludgeon: a case of renal failure and a clavicular mass
  27. Letters to the Editor
  28. Three learning concepts to improve diagnosis and enhance the practice of medicine
  29. Distributed cognition: a framework for conceptualizing telediagnosis in teams
  30. Performance of Fujirebio Espline SARS-CoV-2 rapid antigen test for identifying potentially infectious individuals
https://doi.org/10.1515/dx-2021-0032
Keywords for this article
arthroplasty; D-dimer; diagnosis; periprosthetic joint infection

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. From Camille Nούς to Apollonian and the Dionysian scientists
  4. Review
  5. The role of D-dimer in periprosthetic joint infection: a systematic review and meta-analysis
  6. Mini Reviews
  7. Updated picture of SARS-CoV-2 variants and mutations
  8. Systematic review and cumulative meta-analysis of the diagnostic accuracy of glial fibrillary acidic protein vs. S100 calcium binding protein B as blood biomarkers in observational studies of patients with mild or moderate acute traumatic brain injury
  9. Opinion Papers
  10. The 6C model for accurately capturing the patient’s medical history
  11. Webside manner: maskless communication
  12. Original Articles
  13. Ways that nurse practitioner students self-explain during diagnostic reasoning
  14. Diagnostic reasoning: relationships among expertise, accuracy, and ways that nurse practitioner students self-explain
  15. Perspectives on the current state of pre-clerkship clinical reasoning instruction in United States medical schools: a survey of clinical skills course directors
  16. Use of a structured approach and virtual simulation practice to improve diagnostic reasoning
  17. Analyzing diagnostic errors in the acute setting: a process-driven approach
  18. Morning report goes virtual: learner experiences in a virtual, case-based diagnostic reasoning conference
  19. Stroke hospitalization after misdiagnosis of “benign dizziness” is lower in specialty care than general practice: a population-based cohort analysis of missed stroke using SPADE methods
  20. Discrepancy between emergency department admission diagnosis and hospital discharge diagnosis and its impact on length of stay, up-triage to the intensive care unit, and mortality
  21. Automated capture-based NGS workflow: one thousand patients experience in a clinical routine framework
  22. Short Communication
  23. Characterizing the relationship between diagnostic intensity and quality of care
  24. Case Reports – Lessons in Clinical Reasoning
  25. Lessons in clinical reasoning ‒ pitfalls, myths, and pearls: a case of confusion, disequilibrium, and “picking at the air”
  26. Hickam’s dictum, Occam’s razor, and Crabtree’s bludgeon: a case of renal failure and a clavicular mass
  27. Letters to the Editor
  28. Three learning concepts to improve diagnosis and enhance the practice of medicine
  29. Distributed cognition: a framework for conceptualizing telediagnosis in teams
  30. Performance of Fujirebio Espline SARS-CoV-2 rapid antigen test for identifying potentially infectious individuals
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