Ability of plasma-based or serum-based assays of D-dimer and FDP for diagnosing periprosthetic joint infection: protocol for a prospective single-centre, parallel comparative study

HX, JX and JZ are joint first authors.

Strengths and limitations of this study

• This is a prospective study with enough sample size.

• All related indicators used to diagnose periprosthetic joint infection will be collected.

• This is a single-centre study.

• The diagnostic value of enrolled biomarkers for the patients with inflammatory arthritis and venous thromboembolic disease needed to be further evaluated in the future.

Introduction

Periprosthetic joint infection (PJI) is a catastrophic complication after total hip arthroplasty (THA) or total knee arthroplasty (TKA). It increases hospitalisation costs, prolongs treatment and increases risk of morbidity and mortality.^{1 2} PJI incidence is increasing with the growing number of primary total joint arthroplasties (TJAs).^{3 4} Infection should be detected as early as possible, and certainly before revision surgeries, because it substantially affects planning of treatment and management aimed at preserving the implanted prosthesis and joint function. Detection of PJI is also important for managing patients’ expectations.⁵

One possibility for diagnosing PJI is to assay blood or synovial fluid for appropriate biomarkers.⁶ Blood tests on patients with suspected infection are important because they can be rapidly performed in advance of joint aspiration. A reliable, sensitive biomarker can reduce the rate of missed infections, but the two inflammatory biomarkers currently recommended for diagnosing PJI according to the 2013 International Consensus Meeting (ICM) criteria, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR), are not highly sensitive. Both indices can be normal in infections of certain weakly virulent pathogens, such as Propionibacterium acnes.^6–8

Alternative biomarkers for diagnosing PJI from blood tests may be D-dimer and fibrin degradation product (FDP), both products of fibrinolysis.^{9 10} Levels of D-dimer in plasma have already proven to be a useful marker of lethality for very early-stage blood-borne infections.¹¹ Several studies subsequently reported the diagnostic values of D-dimer and FDP for diagnosis PJI,^{9 12 13} though currently these biomarkers are used in the clinic primarily to exclude venous thromboembolism¹⁴ and monitor postoperative fibrinolysis.¹⁵ And the 2018 revision of ICM criteria had recommended the levels of serum D-dimer as a reference biomarker for diagnosing PJI alongside CRP.¹⁶

Unfortunately, the evidence supporting D-dimer levels as a biomarker of PJI may not be entirely reliable.¹⁷...