Platelet Counts and Mean Platelet Volume As Markers of Clinical Severity in Sickle Cell Disease

Introduction:Platelet counts in peripheral blood could possibly be used as prognostic markers in sickle cell disease (SCD), since these blood elements play an important role in the phenomena of vessel occlusion. In this context, the mean platelet volume (MPV) may also reflect the level of platelet activation, a parameter that is already used in the stratification of thrombotic processes in situations such as acute coronary syndromes. Thus, the aim of this study was to evaluate platelet counts and MPV in SCD as possible prognostic markers for the occurrence of clinical complications and their relation with laboratory markers of inflammation and hemolysis.

Methods:A retrospective chart review was performed on two hundred and sixty-six adult SCD patients (median age 40 years, ranging from 14 to 66), followed from 2002 to 2019, distributed as follows: 156 HbSS, 16 HbSβ⁰, 15 HbSβ⁺ and 79 HbSC. Medical records were reviewed for laboratory data at baseline (first visit); clinical data and hospital admissions were recorded for sickle related complications throughout follow-up: acute chest syndrome, retinopathy, avascular bone necrosis, stroke, priapism, leg ulcers and venous thromboembolism.

Results:The median platelet count was significantly different between the different genotypes (Kruskal-Wallis rank sum test, p < 0.001), with SS: 420 (95-1043) x 10³/uL, Sβ⁰: 406.5 (206 -713), Sβ⁺: 362 (87-925) and SC: 295 (84 -927). This difference may be related to the degrees of inflammation and hyposplenia in each genotype. Regardless of the genotypes, platelet counts in peripheral blood tend to decrease with age (Rô = -0.201, p < 0.001). Interestingly, higher platelet counts are associated with the presence of leg ulcers (Wilcoxon rank sum test with continuity correction, p = 0.03), acute chest syndrome (p= 0.047), higher levels of microalbuminuria (p <0.001) and transfusion load accumulated throughout life (p = 0.03), pointing to a marker of disease severity in this specific cohort. In addition, patients with higher platelet counts tend to have lower hemoglobin (Rô = -0.252, p <0.001) and hematocrit levels (Rô = -0.229, p <0.001), as well as higher RDW (Rô = 0.131, p = 0.032), which could be related to the higher reticulocyte count (Rô = 0.333, p <0.001) suggesting higher levels of hemolysis, corroborated by the higher levels of unconjugated bilirubin (Rô = 0.227, p <0.001). There was also a positive relationship between platelet counts and number of total leukocytes (Rô = 0.343, p <0.001), neutrophils (Rô = 0.272, p <0.001), monocytes (Rô = 0.28, p <0.001) and lymphocytes (Rô = 0.257, p <0.001), probably reflecting an association with exacerbated inflammation and hematopoietic response. MPV index was above normal values in only 10 patients (3.75%) and there were no significant variations between the different genotypes. However, MPV seems to predict the occurrence of retinopathy in SC individuals (Wilcoxon rank sum test with continuity correction, p = 0.05). Moreover, there is an inverse relationship between MPV value and hemoglobin levels (Rô = -0.125, p = 0.041) and hematocrit (Rô = -0.156, p = 0.011), though no correlation with any other laboratory marker or clinical complication.

Discussion: In this cohort of Brazilian patients, we observed that, despite the difference in platelet counts between the genotypes, the increase in platelet counts was related to a greater chance of leg ulcers, Acute Chest Syndrome, microalbuminuria and high transfusion load. Furthermore, platelet number was inversely correlated with hemoglobin and hematocrit levels, and was associated with changes in hemolysis and inflammation markers. MPV was related to the presence of retinopathy in HbSC individuals and MPV elevation was also associated with low levels of hemoglobin and hematocrit. Thus, it is important to evaluate the baseline platelet counts of SCD patients as possible predictor of clinical complications and more severe phenotypes. This simple measure has the potential to raise awareness in the care of these specific patients and to direct greater efforts in the prevention of chronic complications, especially in situations of fewer resources, as this is a cheap and easily available marker.