Monocyte Distribution Width As a Predictor of Alloimmunization in Patients Transfused with Red Blood Cells

Introduction:

In patients who require frequent transfusions, providing compatible units becomes challenging or even life-threatening when patients develop new red cell alloantibodies. The underlying mechanisms that cause some individuals to develop alloantibodies while others do not remain poorly understood. Suggested contributing factors include disease state, HLA polymorphisms, and inflammation. During inflammation, possible mediators involved in alloimmunization are CD16+ monocytes. In proinflammatory states, monocyte activation has been measured using a surrogate marker called the monocyte distribution width (MDW). Since the MDW may predict an activated monocyte state, this marker was investigated as a possible alloimmunization predictor in transfused populations.

Methods:

The study was approved by the Atrium Health Wake Forest Baptist Medical Center Institutional Review Board. In this retrospective case control study, adult and pediatric patients who received at least 1 red blood cell (RBC) transfusion were identified and monitored for the development of red cell antibodies. Transfused patients who developed a new alloantibody were classified as cases, and compared to those who did not develop a new RBC alloantibody. Exclusion criteria were patients with sepsis, or never transfused (including pregnant patients with new antibodies identified). Patients were also excluded if pre-and post-transfusion data were not available. The primary outcome was MDW of pretransfusion samples in alloimmunized patients, compared to controls. Secondary outcomes were CBC parameters, which were collected at the time of first transfusion and identified alloimmunization. We also recorded demographic information and medical diagnoses.

Results:

Initially, 184 transfused patients were included; 12 were excluded for sepsis. Patients were excluded for absence of relevant pre-transfusion data in the electronic medical record (n=22) or lack of available MDW (n=83). Potential controls with hematologic malignancies were found to have higher than average MDW (in the 30s); these were also removed as possible confounders (n=24). The current analysis represents data for 11 cases and 32 controls. Of the 11 cases, 64% were males (36% female), with average age of 58.1. Racial demographics included Black (n=4), White (n=6), and Not specified/other (n=1). The most common clinical diagnoses were sickle cell disease (n=2), chronic kidney disease (n=2) and cardiac disease (n=2).

Of the 32 controls, 66% were males (34% female), with average age of 48.1. Racial demographics included Black (n=9), White (n=18), Not specified/other (n=3). The most common clinical diagnoses were solid tumors (n=11), sickle cell disease (n=7), and anemia/renal disease (n=2, respectively). All patients included in the study were non-Hispanic.

Propensity matching based on age, gender, race, and diagnosis classification (autoimmune, malignancy, sickle cell disease, other) was performed on 9 cases and 9 controls. No statistically significant difference in MDW was found (p=0.566). Of the 9 controls, median pretransfusion MDW was 20.63 [Interquartile range 17.93, 27.26]. Of the 9 cases, median pretransfusion MDW was 20.57 [IQR 18.64, 21.95]

Discussion:

This study evaluated use of the MDW to assess risk of new alloimmunization. While no statistically significant difference was found between the case and control groups, this study was limited by a small sample size. Additionally, this study was limited by availability of the MDW parameter on CBC at the time of transfusion, and a wide variety of diseases was represented within the case and control groups. This study serves a foundation for future investigation into the characterization and potential utility of the MDW beyond its current use. Future directions include characterization of MDW by diagnosis (i.e. sickle cell only, hematologic malignancies), in transfused vs. non-transfused populations, or singly transfused vs. chronically transfused populations.

Onwuemene:Sanofi: Honoraria. Maracaja:Beckman Coulter Diagnostics: Research Funding.