Platelet and Red Blood Cell Volume Indices in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

Abstract

Alterations in the volume of platelets (mean platelet volume, MPV; platelet distribution width, PDW) and erythrocytes (red blood cell distribution width, RDW) have been reported in rheumatoid arthritis (RA) and might serve as diagnostic biomarkers. We conducted a systematic review and meta-analysis of the MPV, PDW, and RDW in RA patients and healthy controls. Relevant articles were searched in PubMed, Web of Science, Scopus, and Google Scholar from inception to June 2022. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist and certainty of evidence was assessed using GRADE. In 23 studies (2194 RA patients and 1565 healthy controls), the RDW, but not MPV or PDW, was significantly higher in RA patients (standardized mean difference, SMD = 0.96, 95% CI 0.78 to 1.15, p < 0.001; moderate certainty of evidence). The substantial heterogeneity observed (I2 = 75.1%, p < 0.001) was virtually removed in a subgroup of prospective studies. In sensitivity analysis, the magnitude of the effect size was not substantially modified by sequentially removing individual studies. There was no significant publication bias. No significant associations were observed between the effect size and pre-defined study or patient characteristics. The results of our study suggest that the RDW might be a useful biomarker for the diagnosis of RA, and complement the clinical information provided by other patient characteristics and laboratory parameters (PROSPERO registration number: CRD42022349432).

Keywords: biomarkers; mean platelet volume; platelet distribution width; red blood cell width; rheumatoid arthritis.

Figure 1

PRISMA 2020 flow diagram.

Figure 2

Forest plot of studies examining the mean platelet volume in patients with rheumatoid arthritis and healthy controls.

Figure 3

Sensitivity analysis of the association between the mean platelet volume and rheumatoid arthritis. For each study, the displayed effect size (hollow circles) corresponds to an overall effect size computed from a meta-analysis excluding that study.

Figure 4

Funnel plot of studies investigating the association between the mean platelet volume and rheumatoid arthritis. Genuine studies are represented by free circles, respectively.

Figure 5

Forest plot of studies examining the mean platelet volume in patients with rheumatoid arthritis and healthy controls according to study design.

Figure 6

Forest plot of studies examining the mean platelet volume in patients with rheumatoid arthritis and healthy controls according to the country where the study was conducted.

Figure 7

Cumulative meta-analysis of the mean platelet volume based on study design (A) and publication year (B).

Figure 8

Forest plot of studies examining the platelet distribution width in patients with rheumatoid arthritis and healthy controls.

Figure 9

Sensitivity analysis of the association between the platelet distribution width and rheumatoid arthritis. For each study, the displayed effect size (hollow circles) corresponds to an overall effect size computed from a meta-analysis excluding that study.

Figure 10

Forest plot of studies examining the platelet distribution width in patients with rheumatoid arthritis and healthy controls according to study design.

Figure 11

Forest plot of studies examining the platelet distribution width in patients with rheumatoid arthritis and healthy controls according to the country where the study was conducted.

Figure 12

Forest plot of studies examining the red cell distribution width in patients with rheumatoid arthritis and healthy controls.

Figure 13

Sensitivity analysis of the association between the red cell distribution width and rheumatoid arthritis. For each study, the displayed effect size (hollow circles) corresponds to an overall effect size computed from a meta-analysis excluding that study.

Figure 14

Funnel plot of studies investigating the association between the red cell distribution width and rheumatoid arthritis after trimming and filling. Dummy studies and genuine studies are represented by enclosed circles and free circles, respectively.

Figure 15

Forest plot of studies examining the red cell distribution width in patients with rheumatoid arthritis and healthy controls according to study design.

Figure 16

Forest plot of studies examining the red cell distribution width in patients with rheumatoid arthritis and healthy controls according to the country where the study was conducted.