Monocyte distribution width (MDW) performance as an early sepsis indicator in the emergency department: comparison with CRP and procalcitonin in a multicenter international European prospective study

Abstract

Background: Early sepsis diagnosis has emerged as one of the main challenges in the emergency room. Measurement of sepsis biomarkers is largely used in current practice to improve the diagnosis accuracy. Monocyte distribution width (MDW) is a recent new sepsis biomarker, available as part of the complete blood count with differential. The objective was to evaluate the performance of MDW for the detection of sepsis in the emergency department (ED) and to compare to procalcitonin (PCT) and C-reactive protein (CRP).

Methods: Subjects whose initial evaluation included a complete blood count were enrolled consecutively in 2 EDs in France and Spain and categorized per Sepsis-2 and Sepsis-3 criteria. The performance of MDW for sepsis detection was compared to that of procalcitonin (PCT) and C-reactive protein (CRP).

Results: A total of 1,517 patients were analyzed: 837 men and 680 women, mean age 61 ± 19 years, 260 (17.1%) categorized as Sepsis-2 and 144 patients (9.5%) as Sepsis-3. The AUCs [95% confidence interval] for the diagnosis of Sepsis-2 were 0.81 [0.78-0.84] and 0.86 [0.84-0.88] for MDW and MDW combined with WBC, respectively. For Sepsis-3, MDW performance was 0.82 [0.79-0.85]. The performance of MDW combined with WBC for Sepsis-2 in a subgroup of patients with low sepsis pretest probability was 0.90 [0.84-0.95]. The AUC for sepsis detection using MDW combined with WBC was similar to CRP alone (0.85 [0.83-0.87]) and exceeded that of PCT. Combining the biomarkers did not improve the AUC. Compared to normal MDW, abnormal MDW increased the odds of Sepsis-2 by factor of 5.5 [4.2-7.1, 95% CI] and Sepsis-3 by 7.6 [5.1-11.3, 95% CI].

Conclusions: MDW in combination with WBC has the diagnostic accuracy to detect sepsis, particularly when assessed in patients with lower pretest sepsis probability. We suggest the use of MDW as a systematic screening test, used together with qSOFA score to improve the accuracy of sepsis diagnosis in the emergency department. Trial Registration ClinicalTrials.gov (NCT03588325).

Keywords: C-reactive protein; Emergency department; MDW; Monocyte volume distribution width; Procalcitonin; Sepsis.

Fig. 1

Flow diagram describing patient screening and enrollment. MDW, monocyte distribution width; SIRS, systemic inflammatory response syndrome; CBC-DIFF, complete blood count with differential; ED, Emergency Department; PCT, procalcitonin; CRP, C-reactive protein; TAT, Turnaround time

Fig. 2

Box plots of MDW baseline values conforming to sepsis classification by Sepsis-2 criteria (A) and Sepsis-3 criteria (B). MDW, monocyte distribution width; SIRS, systemic inflammatory response syndrome

Fig. 3

MDW, WBC and MDW + WBC performance for sepsis diagnosis. A Sepsis-2. B Sepsis-3. C Sepsis-2, low pretest probability population (CRP or PCT not ordered by emergency physician). MDW, monocyte distribution width; WBC, white blood count

Fig. 4

Added value of MDW on sepsis posttest probabilities according to WBC range at presentation. A Sepsis-2 (sepsis pretest probability = 0.17). B Sepsis-3 (pretest 0.09). C Sepsis-2, low pretest probability population (CRP or PCT not ordered by emergency physician. Sepsis pretest probability = 0.065). Cutoff: WBC < 4,000/mm³ or WBC > 12,000, MDW > 21.5, and PCT > 0.25 µg/L. D low pretest probability population per Sepsis-3 (pretest = 0.043). MDW, monocyte distribution width; WBC, white blood count; PCT, procalcitonin; CRP, C-reactive protein

Fig. 5

Sequential assessment of sepsis probabilities according to WBC, MDW and PCT results. Cutoff: WBC < 4,000/mm³ or WBC > 12,000/mm³, MDW > 21.5, PCT > 0.25 µg/L, CRP > 22 mg/L). Pretest probabilities were 0.17 for sepsis-2 and 0.09 for sepsis-3. A PCT by Sepsis-2. B PCT by Sepsis-3. C CRP by Sepsis-2. D CRP by Sepsis-3. MDW, monocyte distribution width; WBC, white blood count; PCT, procalcitonin; CRP, C-reactive protein