Clinical laboratories are accustomed to validating new tests and slotting them into existing protocols. It's a familiar pattern that ordinarily just adds steps to existing processes. But not every diagnostic test belongs in that pattern, and those tests warrant a different conversation. Some tests provide fundamentally different information and do not fit into an existing protocol.

Texas Health Presbyterian Hospital Denton (part of Texas Health Resources) faced this crossroads when its laboratory team began evaluating a rapid host-response diagnostic test for sepsis. Unlike traditional markers that detect pathogens or inflammatory byproducts, host-response tests measure signals from the patient's own immune system, producing a probability of sepsis rather than a downstream indicator.¹ The initial proposal was to add it to the laboratory team’s existing systemic inflammatory response syndrome (SIRS)–based protocol in the emergency department (ED). But this test offered something traditional biomarkers do not: early, actionable data on sepsis risk. It could help clinicians quickly determine whether to escalate or halt sepsis treatment. 

A test that can tell you whether to initiate the entire sepsis response should not be running in parallel with a protocol that has already initiated it. Its value depends on placing it upstream, before the cascade activates, so the result can shape what happens next. That premise became the foundation for a complete workflow redesign.

A different approach to identifying sepsis

The test stratified patients into three bands of sepsis likelihood. Band 1 indicated low probability and supported ruling sepsis out. Band 2 fell into a middle range that required clinical judgment. Band 3 signaled high likelihood and the need for immediate action. 

To make that stratification useful, the workflow had to give each band a clear downstream path. A Band 1 result indicates that the provider should consider an alternative etiology for the patient’s symptoms and not start the sepsis protocol unless there is very high suspicion of sepsis. A Band 2 result indicates that the provider should use their discretion for sepsis treatment. And a Band 3 result triggers a Code Sepsis Alert without waiting on other biomarkers for confirmation. That meant rebuilding the ED protocol around the bands, not adding the bands to the existing protocol.

Rebuilding the ED workflow

In conjunction with ED leadership, lab proposed a new protocol built around the band result. For patients exhibiting signs of sepsis, the workflow began in triage with a focused panel: complete blood count (CBC), comprehensive metabolic panel (CMP), lactic acid, and the host-response test. Blood cultures, antibiotics, and fluid boluses, once automatic for any potentially septic patient, were withheld until the host response test result was returned.

This structure replaced a broad SIRS‑driven approach with a more precise sequence that integrates a host-response sepsis test for any patient suspected of sepsis. It also changed how the lab contributed to the sepsis pathway. Instead of running the same downstream workup on every SIRS-positive patient, an early sepsis test result gave clinicians insights that helped determine whether that workup was needed at all.

Delivering results

In the first six months under the new protocol, the data told a clear story.

• Sepsis activations were cut nearly in half. The daily alert activation rate dropped by 46% for patients not ultimately septic, reducing interruptions and improving efficiency for both ED clinicians and laboratory staff.
• Blood cultures dropped, without compromising care. ED blood cultures decreased by 37%, while ordering among truly septic patients remained stable. Hospital-wide, cultures fell by roughly 30% as admitting teams aligned with the new workflow. For a hospital accustomed to high‑volume cultures driven by SIRS screening, this was a major shift.
• Contamination rates fell sharply. With fewer cultures drawn, the hospital saw an estimated 43% relative reduction in the contamination rate for the ED. Each contaminant can add roughly $4,800 in unnecessary costs due to antibiotics, additional testing, extended observation and delayed discharge, so the financial implications were substantial.³
• Phlebotomy workload stabilized and staffing improved. Previously, phlebotomists were pulled from rounds for every sepsis alert. With fewer alerts and fewer cultures, the lab reallocated staff responsibility improving coverage and job satisfaction.
• Sepsis cases that SIRS would have missed. 43% of Band 3 septic patients did not meet SIRS criteria in the first hour and would not have triggered a sepsis alert under the previous protocol. The host‑response test revealed early sepsis risk that the old protocol would have missed.
• Length of stay decreased. More targeted evaluation contributed to shorter ED and inpatient stays, reflecting a workflow that was both more efficient and more clinically specific.

Texas Health Resources’ (THR’s) experience aligned with the published accuracy data for the host response test: 97% of Band 1 patients were not septic, and Band 3 results strongly correlated with true sepsis.² 

Making the case internally: Cost benefits beyond the lab

A new diagnostic rarely produces line-item savings inside the core lab budget. This one was no exception. The cost of the test itself is a lab expense, but most of the savings show up elsewhere: fewer blood cultures and contaminants in microbiology, fewer unnecessary admissions, shorter stays, and reduced staff time spent responding to sepsis alerts that were never sepsis.

That mismatch is where many lab-led initiatives stall. If a director evaluates the test only against their own budget, the math does not work. If they evaluate it against total cost to the hospital, the math is straightforward.

Lab leaders at THR Denton took the second view from the start. Many laboratory professionals are narrowly focused on their own department, and there are real reasons for that discipline. But when a test increases the lab budget and meaningfully lowers cost for the hospital as a whole, the right answer is to support it. The redesigned workflow at THR Denton produced exactly that result, and that framing is what made the case internally.

What this means for other labs

Not every new test calls for a new protocol. Most do not. But when a diagnostic delivers a fundamentally different kind of information, the question worth asking before validation begins is whether the existing workflow is built to use it.

That question is one that labs are well positioned to raise. Lab directors sit close enough to the data to see when a test is being underused by the protocol around it, and close enough to operations to know what a redesign would actually require. The host-response category is one example. There will be others.

The THR Denton experience does not argue that every lab should redesign its sepsis pathway. It argues that the decision to redesign or absorb should be made deliberately, based on what the test can actually do, rather than by default.

REFERENCES

1. Guillou L, Sheybani R, Jensen AE, et al. Development and validation of a cellular host response test as an early diagnostic for sepsis. PLoS One. 2021;16(4):e0246980. doi:10.1371/journal.pone.0246980.
2. O'Neal HR Jr, Sheybani R, Kraus CK, et al. Cellular host response sepsis test for risk stratification of patients in the emergency department: A pooled analysis. Acad Emerg Med. 2024;31(9):883-893. doi:10.1111/acem.14923. 
3. Geisler BP, Jilg N, Patton RG, Pietzsch JB. Model to evaluate the impact of hospital-based interventions targeting false-positive blood cultures on economic and clinical outcomes. J Hosp Infect. 2019;102(4):438-444. doi:10.1016/j.jhin.2019.03.012.