INFECTION DIAGNOSTICS :: SEPSIS


While widely used in clini- cal practice for prognosis of septic patients, unfor- tunately, both SIRS and qSOFA have been shown to have a poor diagnostic value for sepsis.16, 17, 18 In addition to


the


patient’s physical traits, physicians rely heavily on the laboratory for testing to try to pinpoint sepsis. Blood tests, including the complete blood count with differential (CBC- Diff), sputum testing, and urinalysis are commonly done in the ED to look for sepsis. Procalcitonin (PCT) is produced in response to bacterial infection, and high PCT levels can be in- dicative of a serious infec- tion.19


Similarly, levels of


C-reactive protein (CRP), a substance produced in the liver, increase in response to systemic inflammation or infection.20


While CRP


has been shown to be very sensitive, it is not at all specific; increased levels can indicate, among other things, infec- tion, cancer, or heart disease. The variable nature of sepsis diagno- especially early in disease, and the


Figure 1.


and monocyte distribution width (MDW) have been shown to have potential as biomarkers for sepsis. RDW is an erythrocyte index and re-


sis,21


poor predictive value of existing criteria17 and aforementioned biomarkers highlight the importance of the availability of a unique, early sepsis biomarker to aid clinicians in escalating or de-escalating treatment for patients in the ED. While hundreds of studies have been pub- lished on promising sepsis biomarkers, implementing them in clinical practice in already overworked and understaffed emergency departments (EDs) and clini- cal laboratories has been challenging. A valuable sepsis biomarker needs to flag when risk of sepsis is present, not when it is not. It should be easy to collect, inexpensive, and done on patients regardless of previous sepsis suspicion. Recently, there has been renewed interest in using components of the CBC-Diff to find indicators of sepsis. The CBC-Diff is the most ordered test in the ED and comprises 85% of all blood tests ordered in the ED.22


It is easy to perform, has a


rapid turnaround time, and provides a wealth of health information aiding in a differential diagnosis. Three CBC tests: red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR),


flects heterogeneity in the size of circulat- ing RBCs. When used in patients with suspected sepsis, RDW has been shown to have modest value for predicting a positive blood culture, but limited value for diagnosing sepsis.23


Likewise, NLR


has prognostic value similar to that of C-reactive protein.24


In times of physi-


ological stress, neutrophil count increases and lymphocyte count decreases. The decrease in lymphocyte levels in early sepsis has been correlated with poorer outcomes in septic patients,25,26


but neu-


trophil levels can be influenced by chronic health conditions27


and lymphocyte levels


can be decreased by certain syndromes and noninfectious health conditions28 confounding the ratio.


The value of MDW Monocytes are the body’s first line of defense against pathogens. Part of both the innate and acquired immune responses, monocytes are activated in response to pro-inflammatory signals from infectious organisms and pathogen- associated molecular patterns (PAMPs) such as lipopolysaccharide. Monocytes express receptors for PAMPs and respond


with transcriptional changes and down- stream signaling that ultimately recruit leukocytes to the affected area.29


As with


the size variability of RBCs, the mono- cytes’ response to infection causes an acute change in the size distribution.30


The


monocyte distribution width (MDW) pa- rameter, a regulatory-cleared, in vitro di- agnostic measurement, reflects a change in the volume of circulating monocytes (See Figure 2). The initial feasibility study on the di-


agnostic value of the MDW biomarker in adult patients in the ED showed that it alone or in combination with the WBC count could be used to help establish the severity of infection and risk of sepsis in the ED.33


When used in conjunction with


other clinical parameters, the MDW bio- marker has been shown to improve the early detection of sepsis during the initial ED encounter.31


And while the exact mo-


lecular mechanism for changes in MDW is unknown, it is possible that variations in MDW biomarker correspond with the shift from a localized infection to a systemic, septic inflammatory response.33 One of the biggest benefits of the MDW biomarker is that it is part of the CBC-Diff. There are no additional testing require- ments, thus no impact to workflow. The clinical laboratory is central to patient care, and workflow must be executed in a way


MLO-ONLINE.COM DECEMBER 2022 27


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52