Sickle cell disease is based on the presence of hemoglobin S that develops due to a mutation in the six codon β-globin gene (Piel et al., 2017). Among them, the most common observed type is sickle cell anemia with homozygous hereditary condition causing mutation in hemoglobin (Laurence et al., 2006). Sickle cell anemia incidence is reported as 7 % of the world population (Naoum & Domingos, 1997). According to the reports of the Global Burden of Disease Study, 3.2 million people live with sickle cell disease per year, 43 million people have sickle cell mutation and 176,000 people die due to sickle cell disease-related complications (GBD, Risk Factors Collaborators et al., 2013, 2015). Ischemic complications originating from severe hypoxia are the main reason for mortality and morbidity in patients with sickle cell anemia (Darbari et al., 2013).

Briefly, polymerization of deoxygenated-hemoglobin S is the underlying mechanism of "sickling" of red blood cells, vaso-occlusion, ischemia-reperfusion injury, chronic hemolytic anemia and recurrent vaso-occlusive crises (Lonergan et al., 2001). Patients with sickle cell anemia have progressive organ damage which reduces their life expectancy (Sundd et al., 2019). It has been reported that painful crises and general pathophysiological conditions in these patients are associated with increased inflammatory cytokines such as interleukin-1 beta, tumor necrosis factor-α, interleukin-6, interleukin-17, interleukin-18 as well as oxidative stress markers (Barbu et al., 2020, Castilhos et al., 2017). Additionally, iron, hemoglobin, ferritin and high-sensitivity C-reactive protein (hs-CRP) are critical parameters found in serum which deteriorate in patients with sickle cell anemia in relation to the existing chronic inflammation (Brownell et al., 1986, Krishnan et al., 2010). Hs-CRP is a parameter that shows inflammatory burden and is considered as a biologically relevant biomarker related to sickle cell anemia by reflecting endothelial and coagulation activity (Krishnan et al., 2010). Ferritin is an acute phase reactant and reflects primary iron storage protein in tissues (Wang et al., 2010). Ferritin levels were elevated in the presence of infection and chronic inflammation which reflects the iron balance status in crisis episodes in sickle cell anemia (Brownell et al., 1986, Koerper et al., 1978).

Periodontal diseases have been associated with different systemic diseases through several inflammatory pathways (Akcalı et al., 2015, Matarese et al., 2012, Sari et al., 2022). Patients with sickle cell anemia are vulnerable to infections, therefore, it is claimed that patients are more susceptible to periodontal diseases that are associated with the existing systemic inflammatory status (Kornman et al., 1997). Periodontal diseases can associate with systemic inflammation via circulating pro-inflammatory cytokines (Loos, 2005) and acute phase biomarkers such as hs-CRP (Gomes-Filho et al., 2011), ferritin (Guo et al., 2018).

The main determinants of periodontal diseases are the interaction between the dysbiotic microbiota, and host response through pro-inflammatory markers involved in gingival inflammation and periodontal bone destruction (Martellacci et al., 2019, Matarese et al., 2015). It has been suggested that the amount of periodontal inflamed tissue might be associated with inflammatory mediators as well as bacterial level entering the systemic circulation (Nesse et al., 2009). Clinical attachment level and probing pocket depth (PPD) are linear measures, which cannot calculate the exact amount of inflamed periodontal tissue. In this direction, periodontal inflamed surface area (PISA) was developed as an indicator of disease (Schoffer et al., 2021). PISA values are expressed as the amount of inflamed periodontal tissue by quantifying the surface area of bleeding pocket epithelium in square millimeters (Nesse et al., 2008). Thus, it is suggested that the inflammatory burden due to periodontitis could be quantified by PISA values (Nesse et al., 2008).

The cause of acute painful crisis in sickle cell anemia mainly originates from erythrocyte microvascular occlusion and tissue hypoxia which necessitate hospitalization (Charache et al., 1995). Sickle cell anemia with phenotypic pleiotropy requires complex therapy leading to neglect of oral care due to the prioritization of patients’ vitals. On the other hand, oral health is highly important in this specific cohort, as they are prone to infections and oral infections may worsen the pre-existing condition. However, according to a recent systematic review a guideline is still lacking on the management of oral diseases of patients with sickle cell anemia (Chekroun et al., 2019) meaning more data is needed about the prevalence of periodontal disease in patients with sickle cell anemia. The hypothesis of this study is that the prevalence of periodontal disease and levels of PISA values are similar in patients with sickle cell anemia and systemically healthy individuals. Therefore, the aim of the present study was to evaluate the association between periodontal status, periodontal inflamed surface area and serum acute phase biomarkers levels in patients with sickle cell anemia.