Changes in Heme Levels During Acute Vaso-occlusive Crisis in Sickle Cell Anemia.

OBJECTIVE/BACKGROUND: Sickle cell anemia (SCA) is associated with increased levels of extracellular heme, which is a key mediator of inflammation in this condition. Despite abundant evidence supporting this concept in cell and animal models, few studies addressed the association between heme levels and the development and severity of acute vasoocclusive crises (VOC) in humans. METHODS: A cross-sectional study was conducted in patients with acute VOC. Total extracellular heme levels were measured in both plasma and serum at admission and after convalescence, and correlated with other clinical and laboratory markers of SCA severity. RESULTS: A total of 28 episodes of VOC in 25 patients were included. Heme levels were similar between admission and convalescence, and correlated with the difference between pre and post hemoglobin, and SCA severity estimated by a composite score of clinical and laboratory markers. Heme levels were neither associated with VOC severity nor with markers of hemostasis activation, and were similar to those reported in an independent population of SCA patients at steady state. DISCUSSION: Acute VOC are not characterized by significant increases in total extracellular heme levels. Studies measuring the fraction of free extracellular heme unbound to proteins are warranted to further refine our understanding of the role of heme in acute VOC.

Frequency of Interleukins IL1ß/IL18 and Inflammasome NLRP1/NLRP3 Polymorphisms in Sickle Cell Anemia Patients and their Association with Severity Score.

BACKGROUND: Interleukins IL1ß/IL18 and Inflammasome NLRP1/NLRP3 polymorphisms can change the course of multiple human diseases, both inflammatory as infectious. SNPs these proteins were associated with the constructive activation of the Inflammasome and excessive production of IL-1ß induce a serious autoinflammatory disease, as sickle cell anemia (SCA). The present study aims to association of interleukins IL1ß/IL18 and inflammasome NLRP1/NLRP3 polymorphisms in SCA patients in Amazon region and their association with severity score. METHODS: The study was developed at Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM) with 21 patients diagnosed SCA (HbSS) and 50 Healthy Donor´s. Genetic polymorphisms (SNPs) in interleukins IL1ß/IL18 and inflammasome NLRP1/NLRP3 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real time PCR. Simple and multiple logistic regression were performed to investigate association between the polymorphisms and the SCA and severe score. RESULTS: The genotypes C/C (IL18 -137G/C) and C/A (NLRP3, rs35829419) appear to be risk factors for SCA disease (IL18: G/G vs C/C OR=103.500 [95% CI: 8.32-1287.79, p<0.00001]; IL18: G/G vs G/C OR=7.360 [95% CI: 0.85-63.48, p=0.040]; IL18: G/G vs CC+CG OR=14.481 [95% CI: 1.79-117.32, p=0.002; NLRP3: C/C vs C/A: OR=10.967 [95% CI: 2.41-49.89, p=0.0004]). In addition, only allelic C (IL18 -137G/C) and A (NLRP3) appear to be risk factors for SCA disease (IL18: G vs C OR=6.366 [95% CI: 2.73-14.86, p<0.00001]; NLRP3: C vs A OR=8.383 [95% CI: 2.03-34.62, p=0.005]. No associations were observed between genotypes and alleles with the severity score. CONCLUSION: Evidence of association between the IL18 (rs16944) and NLRP3 (rs35829419) polymorphisms with sickle cell anemia were described. Our results suggest that individuals with genotypes evaluated are associated SCA disease even though it does not influence the severe score.

Epidemiological, clinical, and severity characterization of sickle cell disease in a population from the Brazilian Amazon.

OBJECTIVE/BACKGROUND: Sickle cell disease (SCD) is a chronic inflammatory condition caused by a point mutation in the HBB gene. Here we characterized the clinical presentation of SCD in a population from Amazonas State in northern Brazil, in order to evaluate whether the higher Amerindian ancestry observed in this relatively isolated geographic region would influence the clinical presentation of SCD. METHODS: This was a cross-sectional study characterizing the clinical presentation of SCD patients registered at HEMOAM, Amazon, Brazil. Data were obtained using a structured questionnaire, and by a review of the medical records. RESULTS: Of the 236 SCD patients listed in the historical records, 122 were included in this study. The median age was 15 years, with a male to female ratio of 52:70. The population was characterized by a high level of socioeconomic vulnerability, with only 2.1% presenting a family income above five minimum wages. Homozygous HbS (SS) was the most prevalent form of SCD (89.7%), and the diagnosis of SCD was performed in the context of complications in 92.3% of patients. The median frequency of vaso-occlusive crisis in the past 12 months was 2 (0-10). Using a validated clinical severity score based on clinical and laboratory data, no significant difference could be observed when compared to other populations. CONCLUSION: Our results represent the first comprehensive characterization of epidemiological, laboratorial, and clinical data of SCD in the region of the Brazilian Amazon. Despite the higher contribution of Amerindian ancestry previously demonstrated in this region, the main clinical characteristics of SCD seem similar to those reported in other populations.