Synovasure® Alpha Defensin is a Lab Developed Test (LDT) that uses synovial fluid for the diagnosis of joint infection. The test is available in two formats: Synovasure Alpha Defensin test for Periprosthetic Joint Infection (PJI) and Synovasure Alpha Defensin for Native Septic Arthritis (NSA), The Synovasure test includes three measurements: (1) an immunoassay measurement of synovial fluid alpha defensin levels, (2) an immunoassay measurement of synovial fluid CRP, and (3) a measurement of synovial fluid hemoglobin.
Synovial fluid alpha defensin level is highly accurate in diagnosing periprosthetic joint infection (PJI). The sensitivity of synovial fluid alpha defensin levels for PJI is 97% and the specificity of synovial fluid alpha defensin levels for PJI is 96%. The Synovasure Alpha Defensin test for PJI has been validated against the Musculoskeletal Infection Society (MSIS) guidelines for the diagnosis of PJI.
The false positive rate associated with synovial fluid alpha defensin is ~4%. In our studies, we found that these false positive alpha defensin samples could frequently be identified by their concurrently low synovial fluid CRP value (<3mg/L). Therefore, when the scenario of a high alpha defensin levels and a low CRP in the synovial fluid occurs, we report an accompanying warning that the Synovasure® Alpha Defensin result could potentially be a false positive. For these cases, we recommend that the physician consider all clinical information for final diagnosis.
The synovial fluid hemoglobin level is measured as part of the Synovasure® Alpha Defensin test to quantify the level of lysed blood cells that may have resulted from sample acquisition and shipment. This synovial fluid hemoglobin level is used to adjust the diagnostic threshold of the Synovasure Alpha Defensin test. When there is excessive blood cell lysis present, the result is reported as invalid.
In our studies, Synovasure® has outperformed the LE test strip in both accuracy and the ability to provide valid results. Our data and other studies have shown that the sensitivity of the LE test strip is approximately 80%. The leukocyte esterase test strip also yields a high proportion of unreadable samples due to blood contamination in the synovial fluid (up to 30%).
Synovasure® Alpha Defensin is intended to assess an arthroplasty for Periprosthetic Joint Infection (PJI) prior to surgical revision. At this time, there are studies underway to assess the accuracy of Synovasure Alpha Defensin for PJI in the setting of a reimplantation.
Saline washing is not approved as a collection method for Synovasure® Alpha Defensin, as this will dilute the protein levels in the synovial fluid and potentially yield false negative results.
In the 158 patient study described in the Synovasure® white paper, 27% of infected patients had been treated with antibiotics prior to aspiration. All of these patients had a positive Synovasure Alpha Defensin test for PJI, and the mean alpha defensin level was not different when comparing infected patients being treated with antibiotics versus those not on an antibiotic program.
Several studies have evaluated the performance of Synovasure® Alpha Defensin using the Musculoskeletal Infection Society (MSIS) definition of infection as the “gold standard”.
After the test is completed, results can be sent via email or fax, as noted as the preferred method by practice upon enrollment with CD Diagnostics®. Results can also be accessed online.
Synovasure® results are intended to be used in conjunction with other clinical and diagnostic findings to aid a patient’s diagnosis. Synovasure is intended to determine whether there is an infection present in the synovial fluid at a joint arthroplasty. It is not intended to identify a specific type of infection or establish the origin or severity of an infection. It is intended to provide a physician with a specific positive or negative result for the presence of the alpha-defensin biomarker that is released into the synovial fluid by the patient’s cells while fighting an infection.
Synovasure® provides a positive or negative result for alpha defensin. Standard culture methods are available at CD Laboratories® for the identification of the organism. The initial Synovasure result will be reported within 24 hours of sample receipt, but the culture results (if requested) will be reported as “pending” until the test is complete. Culture negative results are reported after they are negative for the full culture period.
The physician’s office can track the shipment using the tracking number on the FedEx return label (or photocopy the label) on the pouch provided.
There are specific instructions on the Test Submission Document to ensure that the samples are picked up and delivered in a timely fashion. To schedule your “prepaid pickup”. Call 1-800-463-3339 (1-800-GOFEDEX) or schedule online through www.fedex.com.
Note: Packages CANNOT be placed in a FedEx dropbox.
Fill out the Synovasure® Enrollment document and fax to CD Diagnostics® at 443-279-8379. Enrollment is typically processed within 24 hours of receipt. Once received, you will be sent kits to have on hand in your office. Next, ask your Zimmer Biomet rep to familiarize your staff with the paperwork and submission process. Finally, make sure you always have 2-3 Synovasure kits readily accessible in your practice or satellite office. If you need more kits, contact CD Diagnostics Customer Service at 888-981-8378. Once you are shipping samples routinely, you will receive kits by auto replenishment.
The Synovasure® kit contains the materials needed to send synovial fluid to CD Laboratories® includes:
- Submission Instructions Sheet
- 95 kPa Specimen Transport Biohazard Bag
- Specimen Tubes
- Test Requisition Form
- Biological Specimen Box
- Prepaid FedEx Pouch for Biological Specimens
- Prepaid FedEx shipping label
Note: Clinical laboratory kits do not include forms or specimen tubes. Forms are provided electronically upon enrollment.
If you aspirate a synovial fluid sample on Friday or over the weekend, please refrigerate the specimen and ship it on Monday for Tuesday delivery. A sample can be refrigerated for up to 3 days.
The cost for the Synovasure® Panel is $93.00. If you opt to have cultures done in addition to Synovasure, the cost is an additional $25 for aerobic and $25 for anaerobic cultures, with additional charges for bacterial identification and antibiotic sensitivity (these differ based on the organism (bacteria vs. fungus) and number of organisms grown in culture).
When you submit a synovial fluid sample, you will also complete a Test Requisition form. This document accompanies the sample to the lab and the patient billing information must be included on the form. Upon performing the test, CD Laboratories® will bill the patient’s insurance. If the insurance declines coverage, the patient is responsible to cover the cost.
When you aspirate a sample of synovial fluid, you will continue to charge for aspiration as you normally would. Upon running the Synovasure® test, CD Laboratories® will bill the patient’s insurance for the tests selected on the Test Requisition form. In cases in which the arthrocentesis is being billed by the hospital, the hospital is required to bill Medicare for the Synovasure test. CD Laboratories is required to charge the hospital for the services performed and the hospital will be paid pursuant to Medicare policies for reimbursement of inpatient or outpatient services. A discount will be provided to hospital laboratories that bill Synovasure tests directly.
Specimen kits are provided free of charge to a practice and include a prepaid FedEx label to ship specimens to CD Laboratories® for testing.
Most claims are reimbursed by insurance, at various rates depending on the patient’s insurance. Occasionally insurance will decline payment due to network requirements or the patient’s deductible.
Synovasure® is exclusively serviced by CD Laboratories®, a subsidiary of Zimmer Biomet. At the laboratory, results are determined and returned to the clinician within 24 hours of receipt. CD Laboratories (CLIA License# 21D0216863) is located in Baltimore, MD.
The Comprehensive Periprosthetic Joint Infection (PJI) panel includes:
- Synovasure® Alpha Defensin test
- Synovasure Neutrophil Elastase test
- Cell Count
Note: Tests are not currently available in the State of New York.
At this time, the Synovasure® Alpha Defensin test for PJI has only been validated for use with total joint replacements. To date, clinical studies to assess performance with partial joint replacements have not been conducted.
In the 158 patient study described in the Synovasure® white paper, 23% of patients had a concurrent diagnosis of an inflammatory condition. Concurrent inflammatory arthritis in patients did not affect the peformance of the Synovasure Alpha Defensin test, nor were the alpha defensin levels significantly different in this population.