Serum D-Dimer Test Is Promising for the Diagnosis of Periprosthetic Joint Infection and Timing of Reimplantation

TLDR: Serum D-dimer outperformed both ESR and serum CRP, with a sensitivity and specificity of 89% and a specificity of 93%, and may have a great utility for determining the optimal timing of reimplantation.

Abstract: Background:Despite the availability of a battery of tests, the diagnosis of periprosthetic joint infection (PJI) continues to be challenging. Serum D-dimer assessment is a widely available test that detects fibrinolytic activities that occur during infection. We hypothesized that patients with PJI m

Figures

Table 3.

Table 6. Culture results in patients who underwent revision surgery due to periprosthetic joint infection.

Table 7. Periprosthetic joint infections with negative culture. The false-negative laboratory values are marked in yellow (Thresholds are based on the Musculoskeletal Infection Society diagnostic criteria for periprosthetic joint infection. D-dimer’s threshold [850 ng/mL] is calculated based on the results of this study).

Table 2. Demographics of the study groups. Group A: Primary arthroplasty, Group B: Aseptic 365 revisions, Group C: First stage of a two stage exchange revision protocol, Group D: Second stage 366 of a two stage exchange protocol (reimplantation), Group E: Patients with infections other than 367 periprosthetic joint infection. 368 369

Table 4. Performance of the serum tests for diagnosing periprosthetic joint infection. ESR: 383 Erythrocyte Sedimentation Rate, CRP: C-reactive Protein. 384 385

Table 1. Definition of PJI according to the musculoskeletal infection society and the threshold 360 for the minor diagnostic criteria. 361 362

Full text

Thomas Jefferson University Thomas Jefferson University
Jefferson Digital Commons Jefferson Digital Commons
Rothman Institute Faculty Papers Rothman Institute
9-6-2017
Serum D-Dimer Test Is Promising for the Diagnosis of Serum D-Dimer Test Is Promising for the Diagnosis of
Periprosthetic Joint Infection and Timing of Reimplantation. Periprosthetic Joint Infection and Timing of Reimplantation.
Alisina Shahi
Thomas Jefferson University
Michael M. Kheir
Thomas Jefferson University
Majd Tarabichi
Thomas Jefferson University
Hamid R.S. Hosseinzadeh
Rowan University
Timothy L. Tan
Thomas Jefferson University
See next page for additional authors
Follow this and additional works at: https://jdc.jefferson.edu/rothman_institute
Part of the Orthopedics Commons
Let us know how access to this document bene>ts you
Recommended Citation Recommended Citation
Shahi, Alisina; Kheir, Michael M.; Tarabichi, Majd; Hosseinzadeh, Hamid R.S.; Tan, Timothy L.;
and Parvizi, Javad, "Serum D-Dimer Test Is Promising for the Diagnosis of Periprosthetic Joint
Infection and Timing of Reimplantation." (2017).
Rothman Institute Faculty Papers.
Paper 96.
https://jdc.jefferson.edu/rothman_institute/96
This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital
Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is
a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections
from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested
readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been
accepted for inclusion in Rothman Institute Faculty Papers by an authorized administrator of the Jefferson Digital
Commons. For more information, please contact: JeffersonDigitalCommons@jefferson.edu.

Authors Authors
Alisina Shahi, Michael M. Kheir, Majd Tarabichi, Hamid R.S. Hosseinzadeh, Timothy L. Tan, and Javad
Parvizi
This article is available at Jefferson Digital Commons: https://jdc.jefferson.edu/rothman_institute/96

1
Serum D-dimer is a Promising Test for the Diagnosis of Periprosthetic Joint Infection and
1
Timing of Reimplantation
2

2
ABSTRACT:
3
Background: Despite the availability of battery of tests, the diagnosis of periprosthetic joint
4
infection (PJI) continues to be challenging. Introduction of synovial biomarkers has improved
5
the diagnosis, however, obtaining synovial fluid is invasive, occasionally impossible and carries
6
the risk of introduction of infection into the joint. There is a desperate need for a serum marker
7
of PJI. Serum D-dimer is a widely available test that detects fibrinolytic activities that occurs
8
during infection. We hypothesized that patients with PJI may have a high level of circulating D-
9
dimer and that the presence of high levels of serum D-dimer may be a sign of persistent infection
10
in patients awaiting reimplantation.
11
Methods: This prospective study was initiated to enroll patients undergoing primary and revision
12
arthroplasty. Our cohort consists of 245 patients undergoing primary arthroplasty (N=23),
13
revision for aseptic failure (N=86), revision for PJI (N=57), patients undergoing reimplantation
14
(N=29), and a group of patients with infection in a different site than the joint (N=50). PJI was
15
defined using the Musculoskeletal Infection Society criteria. All patients in the study had serum
16
D-dimer, erythrocyte sedimentation (ESR), and C-reactive protein (CRP) measured
17
preoperatively.
18
Results: The median D-dimer was statistically higher (p<0.0001) in PJI patients
19
(1,100ng/mL,range:243-8,487ng/mL) compared to (299ng/mL,range:106-6,381ng/mL) in
20
patients with aseptic failure. Using the Youden’s index, 850ng/mL was determined as the
21
optimal threshold for serum D-dimer for diagnosis of PJI. Serum D-dimer outperformed both the
22
ESR and the serum CRP with a sensitivity of 89% and a specificity of 93%. ESR and CRP had a
23
sensitivity of 73% and 79% and a specificity of 78% and 80%, respectively. The sensitivity and
24

3
specificity of ESR and CRP combined was 84%(95%CI:76-90%) and 47%(95%CI:36-58%),
25
respectively.
26
Conclusion: It appears that the serum D-dimer is a promising marker for diagnosis of PJI. This
27
test may also have a great utility for determining the optimal timing of reimplantation. This study
28
demonstrates that serum D-dimer can be utilized as a screening test for PJI.
29
Level of Evidence: Diagnostic Level II.
30

Frequently asked questions

Q1. How many inflammatory factors have been reported in endothelial cells and monocytes?

25,26 Inducible tissue factor expression has been reported in endothelial 196 cells and monocytes following in vitro augmentation with proinflammatory factors, such as 197 cytokines (IL-1, IL-6, and tumor necrosis factor [TNF]). 

Q2. What were the conditions that were recorded in the study?

91 Sex, age, joint, and comorbid conditions including systemic inflammatory disease such as 92 rheumatoid arthritis, systemic lupus erythrematosus, psoriasis, polymyalgia rheumatica, 93 sarcoidosis, inflammatory bowel disease, gout, hepatitis B and C, lymphocytic leukemia, 94 myelodysplastic syndrome, multiple myeloma were recorded. 

Q3. How many factors can activate the coagulation cascade?

Studies have also shown that coagulation 194 factors that are formed following activation of the coagulation cascade can have 195 proinflammatory effects. 

Q4. What is the role of D-dimer in the prevention of systemic damage?

The increased fibrinolytic activity and 202 generation of byproducts such as D-dimer are believed to localize the infecting organisms or 203 inflammatory cells and thus prevent their systemic damage. 

Q5. What is the common reason for the abandonment of D-dimer?

D-dimer has been traditionally used as a screening test for detecting deep venous thrombosis 71 (DVT) but largely abandoned because of its poor performance. 

Q6. What are the commonly used serum markers for PJI?

Although numerous serum markers 40 for PJI have been evaluated in the past including interlukin-6 (IL-6) and others 1, the most widely 41 used serums tests for diagnosis of PJI are erythrocyte sedimentation rate(ESR) and C-reactive 42 protein(CRP)2. 

Q7. What is the protocol for a revision arthroplasty?

As part of the 99 standard protocol at their institution, surgeons obtain at least three intraoperative tissue culture 100 specimens from patients undergoing revision arthroplasty. 

Q8. how many folds of D-dimer in foals with septic joint disease?

In fact 199 an older study by Ribera et al.14 demonstrated that the concentration of synovial fluid D-dimer 200 increased several folds in foals with septic joint disease, endorsing the fact that D-dimer is 201 involved in mediating inflammation/infection in the joint. 

Q9. How many patients underwent revision 162 surgery?

161 Seventeen patients in their cohort required reoperations (Table 5). 15 patients underwent revision 162 surgery for infection; of which, 10 patients subsequently were reimplanted. 

Q10. How many patients had a serum D-dimer test?

All patients in the study had serum 16 D-dimer, erythrocyte sedimentation (ESR), and C-reactive protein (CRP) measured 17 preoperatively. 

Q11. What were the patients with a history of hypercoagulation disorders?

Patients undergoing 82 primary and revision arthroplasty were included except those with any type of skin ulcer, 83 hematoma, recent trauma or dislocation (within two weeks), visible ecchymosis, prosthetic heart 84 valves, and those with a history of hypercoagulation disorders. 

Q12. what was the mean d-dimer in the primary arthroplasty cohort?

The mean D-dimer was 129 212.5 ng/mL (range: 150-430 ng/mL) in the primary arthroplasty cohort, 399.9 ng/mL (range: 130 106-2,571 ng/mL) in the aseptic revision arthroplasty cohort, 1,634 ng/mL (range: 243-8,487 131 ng/mL) in PJI patients, 806.7 ng/mL (range: 170-6,381 ng/mL) in the reimplantation group, and 132 451 ng/mL (range: 150-1,420 ng/mL) in patients with infection in sites other than a joint (Figure 133 2).