Monocyte Distribution Width as a New Indicator of Sepsis in High-Risk Patients
Most septic patients are first encountered in the emergency department, where sepsis detection is often delayed, partly due to a lack of effective biomarkers. The study presented below evaluated the diagnostic accuracy of monocyte distribution width in peripheral blood alone and in combination with white blood cell count evaluation for early sepsis detection.
Introduction
Sepsis is a major cause of hospital mortality and a significant financial burden on healthcare systems worldwide. Delays in diagnosing and treating sepsis are common in acute care due to inadequate detection. Delays in sepsis intervention timing in the earliest stage of this condition correlate with adverse clinical outcomes and higher care costs. Therefore, new protocols and biomarkers are being proposed to improve early sepsis detection. Existing biomarkers, however, have limited utility for early sepsis detection, as they cannot accurately distinguish sepsis from other more common conditions in acute care. As the infection progresses, symptoms of the host's escalating immune response, such as fever, tachycardia, tachypnea, and elevated circulating white blood cell counts, begin to appear.
A recent study demonstrated that acute changes in monocyte size, or monocyte distribution width (MDW), best differentiate sepsis from other acute conditions and further that MDW in combination with white blood cell counts detects early sepsis better than MDW or white blood cell counts alone. The authors of the following study sought to further develop the initial data.
Evaluated Patient Population
This multicenter study included patients aged 18-89 years who had a complete blood count tested in the emergency department and remained hospitalized for at least 12 hours (n = 2158). In the previous study, an MDW cut-off value of 20 U was determined, which had optimal sensitivity and specificity for defined sepsis parameters. Patients were further categorized according to the "sepsis-2" criteria (a 1992 definition including clinical signs and laboratory parameters) and "sepsis-3" criteria (a 2016 definition per SOFA score). The presence of infection in the patient always had to be confirmed.
Results
Out of 2158 patients, 385 met the criteria for diagnosis according to "sepsis-2" (17.8%) and 243 according to "sepsis-3" (11.3%). Monocyte distribution width > 20 U distinguished sepsis from all other conditions included in the "sepsis-2" criteria (AUC 0.79; 95% confidence interval [CI] 0.76-0.82) or in the "sepsis-3" criteria (AUC 0.73; 95% CI 0.69-0.76). Negative predictive values for MDW ≤ 20 U for "sepsis-2" were 93% and for "sepsis-3" 94%. MDW > 20 U in combination with abnormal white blood cell counts further improved sepsis detection (AUC 0.85; 95% CI 0.83-0.88). Normal leukocyte distribution and monocyte width indicated a 6x lower likelihood of a septic condition.
Discussion
MDW could add value to current sepsis detection protocols. Complete blood counts with differential are commonly evaluated for all patients in the emergency department and form part of the initial examination for acute conditions, aiding in differential diagnosis, which may also include decisions regarding sepsis diagnosis. White blood cell counts serve as a laboratory standard for initial detection of serious infections; abnormal white blood cell counts are 88% sensitive for sepsis detection, but their specificity is low.
This study showed that MDW in combination with white blood cell counts accelerates sepsis detection. Unlike other available sepsis biomarkers such as procalcitonin, C-reactive protein, and lactate, whose values are typically determined after the patient is admitted from the emergency department, MDW could be automatically reported with the complete blood count and differential, thus serving to detect possible sepsis already with the first test results for the patient in the emergency department.
Conclusion
Changes in the volume of monocytes in peripheral blood, specifically an increase in monocyte distribution width, effectively identify septic patients and patients with infections at increased risk of progression to sepsis. When combined with the evaluation of white blood cell counts within the assessment of complete blood count and differential, monocyte distribution width accelerates sepsis detection and is expected to improve care decision-making related to early detection and treatment of septic conditions.
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Source: Crouser E. D., Parrillo J. E., Seymour C. W. et al. Monocyte distribution width: a novel indicator of sepsis-2 and sepsis-3 in high-risk emergency department patients. Crit Care Med 2019; 47 (8): 1018-1025, doi: 10.1097/ccm.0000000000003799.
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