Periodontitis and circulating blood cell profiles: a systematic review and meta-analysis

Periodontitis is a chronic inflammatory disease with local and systemic implications. Evidence suggests consistent hematologic changes associated with periodontitis. Our aim was to critically appraise the available evidence on hemogram, leukogram, and thrombogram alterations in otherwise healthy patients suffering from periodontitis when compared with controls. For this systematic review (SR), we searched MEDLINE, Web of Science, EMBASE, and the Cochrane Library (CENTRAL) for studies published up to June 2020. Both observational and interventional studies with baseline standard hematologic levels were included. Outcomes of interest were baseline hemogram, leukogram, and thrombogram values and the impact of periodontitis treatment on these outcomes. Upon risk of bias assessment, data extraction and both qualitative and quantitative (standardized mean differences) analyses were performed. Random-effects meta-analyses were performed to provide pooled estimates. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed (PROSPERO Reg. No. CRD42020164531). A total of 45 studies, eight intervention and 37 case-control studies, were identified after the final search of 3,012 titles. Following quality assessment, 43 articles were deemed to have low risk of bias, and two articles moderate risk. Meta-analyses confirmed that periodontitis was associated with both white and red cell lineages. Severe chronic periodontitis was associated with greater white blood cell counts (mean difference [MD] = 0.53, 95% confidence interval [CI]: 0.26-0.79) when compared with controls. Periodontitis was associated with a larger number of neutrophils (MD = 7.16%, 95% CI: 5.96-8.37) and lower mean platelet volume (MD = 0.30 fL, 95% CI: 0.49 to -0.10) compared with healthy participants. Nonsurgical periodontal treatment was associated with a decrease in white blood cell (WBC) levels (MD = 0.28 10⁹/L, 95% CI: -0.47 to -0.08) in patients with chronic periodontitis. Periodontitis is associated with hematologic changes (Strength of Recommendation Taxonomy [SORT] A recommendation). Higher WBC levels, higher neutrophil levels, higher erythrocyte sedimentation rate, and lower mean platelet volumes are the most common blood count findings. The association between periodontitis and WBC could be causal in nature. Further assessment to determine whether periodontitis causes changes in circulating blood cells and to identify the molecular mechanisms underlying these associations is warranted.