Hiding in Plain Sight: The Case for MDW Parameter in Early Sepsis Screening

Issue Writ Large

Hematology tests such as the complete blood count (CBC) often reveal differences in the sizes of red and white blood cells.

While some degree of variability is considered normal, a predominance of cells that are bigger or smaller will cause the size distribution to widen providing important information about potential underlying disease states. Using modern, automated hematology analyzers, such size distributions can be easily determined and rapidly reported in the electronic health record (EHR). The time-tested utility of this is best represented by red cell distribution width (RDW), a parameter that is routinely incorporated into standard CBC reports and used regularly in clinical practice for the diagnosis and differentiation of many forms of anemia. 

With respect to white blood cells, size differences also matter but it's a little more complicated as there are multiple different cell subtypes, each with a differing morphology, making a single white cell distribution width impossible to define. Nonetheless, as an indicator of immune system activation, the white blood cell (WBC) count has long been used as a measure of potential infection with total and cellular subtype counts as well as relative ratios serving as important diagnostic parameters. 

Despite universal acceptance of its role in the diagnosis of infection, the WBC count is recognized as an imperfect biomarker with high false negative and false positive rates. This has led to a growing interest in additional biomarkers to enhance diagnostic accuracy, especially for cases of suspected sepsis, where early intervention may be lifesaving. As the leading cause of hospitalization in the U.S., sepsis is responsible for nearly 350,000 deaths each year and $62 billion in associated healthcare spending. Not surprisingly, patients, providers, payers, healthcare systems, industry partners, and even the US congress (which incorporated specific funding and directives in its recently passed $1.7 trillion Omnibus spending bill) are interested in finding ways to improve sepsis outcomes through better diagnosis and treatment.¹

Solution De Facto?

Virtually all adjuncts for sepsis diagnosis require ordering an additional test, often with a specific tube or sampling time frame. However, many of these tests are not available on existing lab equipment and some even require send-out to an external facility. As such, the ability to enhance the diagnostic yield from existing equipment using routinely obtained tests like the CBC has enormous appeal. Monocytes stand out as the first white cells to get activated upon pathogen exposure, making them an ideal, early indicator of a brewing infection. In response to such activation (Figure), monocytes swell and release inflammatory mediators to prime the immune system. Consequently, the Monocyte Distribution Width (MDW) increases and if persistent, serves as a reliable indicator of developing immune dysregulation – a critical precursor to impending sepsis. Akin to RDW as a biomarker in anemia, MDW serves as a true parameter of cellular response (in this case, to infection), with a high degree of causal specificity. Approved by the US Food and Drug Administration with an established cut-point of 20* units (U), MDW has been shown in more than 21,000 patients globally to be a highly effective early indicator of sepsis and septic shock,^2–6 significantly enhancing diagnostic performance of the CBC itself while displaying better consistency than lactate or c-reactive protein.

 Screening with MDW has a cascade effect, shortening the time to an accurate diagnosis which enables more rapid initiation of appropriate therapy while enhancing throughput and reducing emergency department length of stay – all of which ultimately contribute to better sepsis outcomes. Of septic patients presenting to the emergency department, 31% had normal WBC levels, and the presence of an abnormal MDW value correlated with a 6-fold higher risk of sepsis.² Moreover, improving early identification of sepsis can help to reliably triage patients so that timely care can be administered.⁷ This not only may improve patient satisfaction but also may help the facility appropriately allocate resources leading to decreased crowding in the emergency department⁸ and increased facility revenue.^9,10 

Many hospitals in the US (approximately one out of every four) have the Beckman Coulter Hematology analyzers needed to measure MDW providing potential for a sizeable impact. To implement MDW, the parameter simply has to be activated on the analyzer and results added to standard EHR reporting for a CBC with differential. However, to date just under 30% of MDW-capable hospitals have begun reporting the parameter. Further, only 25% of physicians in locations that have activated MDW report using it regularly for sepsis screening. We must drive knowledge and awareness of this powerful new parameter to improve adoption. 

Carpe Diem

To realize the potential benefit of MDW, a systems change approach is clearly needed. In facilities that currently run CBCs on an MDW-capable Beckman Coulter Hematology analyzer, a simple solution for early identification of sepsis exists that may be hiding in plain sight. By aligning goals of hospital leadership with those of clinicians and laboratory medicine specialists, advancements like MDW can be brought out of the shadows with intentionality and purpose, ensuring that patients with suspected sepsis get the best care possible. 

* 20 U in K2EDTA venous samples; 21.5 U in K3EDTA venous samples

References: 

1. Congress Approves Sepsis Funding and Issues Sepsis Directives in the FY23 Budget in Historic First. January 25, 2023. Accessed March 14, 2023. https://www.prnewswire.com/news-releases/congress-approves-sepsis-funding-and-issues-sepsis-directives-in-the-fy23-budget-in-historic-first-301729624.html
2. Crouser ED, Parrillo JE, Martin GS, et al. Monocyte distribution width enhances early sepsis detection in the emergency department beyond SIRS and qSOFA. J Intensive Care. 2020;8:33. doi:10.1186/s40560-020-00446-3
   
3. Crouser ED, Parrillo JE, Seymour C, et al. Improved early detection of sepsis in the ED with a novel monocyte distribution width biomarker. Chest. 2017;152(3):518-526. doi:10.1016/j.chest.2017.05.039
   
4. Crouser ED, Parrillo JE, Seymour CW, 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
   
5. Malinovska A, Hinson JS, Badaki-Makun O, et al. Monocyte distribution width as part of a broad pragmatic sepsis screen in the emergency department. Journal of the American College of Emergency Physicians Open. 2022;3(2):e12679. doi:10.1002/emp2.12679
   
6. Hausfater P, Robert Boter N, Morales Indiano C, et al. 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. Crit Care. 2021;25(1):227. doi:10.1186/s13054-021-03622-5
   
7. Hinson JS, Martinez DA, Schmitz PSK, et al. Accuracy of emergency department triage using the Emergency Severity Index and independent predictors of under-triage and over-triage in Brazil: a retrospective cohort analysis. Int J Emerg Med. 2018;11(1):3. doi:10.1186/s12245-017-0161-8
   
8. Farley H. Emergency Department Crowding: High Impact Solutions. American College of Emergency Physicians; 2016:1-19.
   
9. Levin S, Toerper M, Hamrock E, et al. Machine-Learning-Based Electronic Triage More Accurately Differentiates Patients With Respect to Clinical Outcomes Compared With the Emergency Severity Index. Ann Emerg Med. 2018;71(5):565-574.e2. doi:10.1016/j.annemergmed.2017.08.005
   
10. Levin S, Toerper M, Hinson J, et al. 294 Machine-Learning-Based Electronic Triage: A Prospective Evaluation. Ann Emerg Med. 2018;72(4):S116. doi:10.1016/j.annemergmed.2018.08.299