Diagnostic Utility of a Novel Point-of-Care Test of Calprotectin for Revision Total Knee Arthroplasty

Calprotectin is a biomarker closely associated with leucocytes in general, and is present in
high volumes in neutrophil cells. Calprotectin is also produced by infiltrating monocytes and
macrophages, where calprotectin is released upon phagocytosis. In neutrophils, calprotectin
is stored intracellularly and are released upon activation of the cell. The determination of
number of neutrophils and proportion of neutrophils out of total number of inflammatory cells
is a diagnostic strategy commonly used in diagnosis of infection. Upon encounter with a
pathogen, neutrophils have several strategies to fight infections , and produce high-levels
of calprotectin. Activation of neutrophils, and release of calprotectin, can be for any
reason causing activation of the complement system and aseptic Inflammatory responses.
Moreover, Calprotectin is a danger associated molecular patterns (DAMP) signal influencing
the inflammatory responses. The level of activated neutrophils in PJI provide basis of the
presence of calprotectin in the synovial fluid of PJI patients, and thus, for calprotectin as
a potential biomarker for PJI. Calprotectin-levels in the synovial fluid do not merely
reflect the level of leucocytes and neutrophils present in the synovial fluid, but levels are
correlated to the WBC content. Calprotectin is likely to reflect the number of activated
cells and surpass the diagnostic accuracy of total WBC counts and neutrophil percentage for
PJI diagnosis.

A level of calprotectin of 50 mg/L in the synovial fluid has very good diagnostic accuracy
for PJI, supported by area under the curve values of more than 0.9. In a subgroup analysis
for patients with chronic PJI, a NPV of 97% was observed. The excellent NPV may assist in the
orthopaedic clinic to rule out the presence of infection and consider diagnostic alternatives
for aseptic loosening and pain revision of the joint patient. A rapid and accurate
distinction between these two causes is important as PJI and aseptic loosening are managed
differently with regards to surgical Intervention and followup.

Point of Care Test diagnostics by lateral flow devices provides reliable test results within
minutes of sample collection. Currently, Calprotectin can be detected by such lateral flow
devices (developed by Orthogenics, Tromsø, Norway). The speed and ease of use of this test
allows for diagnosis at patient's bed side. These tests can be applied in the physician's
office, operating room, an ambulance, the home, the field, or in the hospital. As the results
are timely they allow rapid diagnostic and identifies treatment alternatives for the patient.
This technology empowers clinicians to make decisions at the "point-of-care" and can have
significant impact on health care delivery and ability to address challenges of health
disparities. However, it is important to validate the diagnostic utility of calprotectin POC
in a diverse set of patients undergoing revision arthroplasty.

Inclusion Criteria:

- Subject is ≥18 years of age

- Patient with a diagnosis of OA (for primary TKA only)

- Subject has had no recent injections or surgeries of the joint (within past 6 weeks)

- Subject has or will have all of the medical tests required to allow MSIS
classification

- Subject signs informed consent form

Exclusion Criteria:

- Subjects with a diagnostic synovial fluid specimen collection within the past 7 days

- Results are not available for medical tests required to perform MSIS classification

- Sample was obtained via lavage

- Quantity not sufficient (at least 1 ml required)