BackgroundThe search for sickle cell disease (SCD) prognosis biomarkers is a challenge. These markers identification can help to establish further therapy, later severe clinical complications and with patients follow-up. We attempted to study a possible involvement of levels of high-density lipoprotein cholesterol (HDL-C) in steady-state children with SCD, once that this lipid marker has been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities, important aspects to be considered in sickle cell disease pathogenesis.MethodsWe prospectively analyzed biochemical, inflammatory and hematological biomarkers of 152 steady-state infants with SCD and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records.ResultsOf the 152 infants investigated had a significant positive association of high-density lipoprotein cholesterol with hemoglobin (P < 0.001), hematocrit (P < 0.001) and total cholesterol (P < 0.001) and a negative significant association with reticulocytes (P = 0.046), leukocytes (P = 0.015), monocytes (P = 0.004) and platelets (P = 0.005), bilirubins [total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and indirect bilirubin (P < 0.001], iron (P < 0.001), aminotransferases [aspartate aminotransferase (P = 0.004), alanine aminotransferase (P = 0.035)], lactate dehydrogenase (P < 0.001), urea (P = 0.030), alpha 1-antitrypsin (P < 0.001), very low-density lipoprotein cholesterol (P = 0.003), triglycerides (P = 0.005) and hemoglobin S (P = 0.002). Low high-density lipoprotein cholesterol concentration was associated with the history of cardiac abnormalities (P = 0.025), pneumonia (P = 0.033) and blood transfusion use (P = 0.025). Lipids and inflammatory markers were associated with the presence of cholelithiasis.ConclusionsWe hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by low HDL-C with hypertriglyceridemia and high VLDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. Additional studies are warranted to test this hypothesis and the probably mechanisms involved in this complex network of markers and their role in SCD pathogenesis.
Alpha-1 antitrypsin (AAT) is an inhibitor of neutrophil elastase and a member of the serine proteinase inhibitor (serpin) superfamily, and little is known about its activity in sickle cell disease (SCD). We hypothesize that AAT may undergo changes in SCD because of the high oxidative stress and inflammation associated with the disease. We have found high AAT levels in SCD patients compared to controls, while mutant genotypes of SERPINA1 gene had decreased AAT levels, in both groups. AAT showed negative correlation with red blood cells, hemoglobin (Hb), hematocrit, high-density lipoprotein cholesterol, urea, creatinine, and albumin and was positively correlated with mean corpuscular Hb concentration, white blood cells, neutrophils, Hb S, bilirubin, lactate dehydrogenase, ferritin, and C-reactive protein. Patients with higher levels of AAT had more infection episodes (OR = 1.71, CI: 1.05–2.65, p = 0.02), gallstones (OR = 1.75, CI: 1.03–2.97, p = 0.02), and had more blood transfusions (OR = 2.35, CI: 1.51–3.65, p = 0.0001). Our data on AAT association with laboratory indices of hemolysis and inflammation suggest that it may be positively associated with SCD severity; the negative correlations with renal parameters suggest a cytoprotective mechanism in SCD patients. In summary, AAT may need to be included in studies related to SCD and in the discussion of further therapeutic strategies.
Background: Sickle cell disease (SCD) is a heredity group of anemia characterized by hemolysis, chronic inflammation, and vaso-occlusive/painful crisis. The heme is a product of erythrocytes' lyses and is increased in hemolytic diseases. Objectives: To investigate associations between hematological/biochemistry biomarkers and total plasma heme levels between SCD patients groups (in crisis and in steady-state) and healthy controls. To identify molecules related to hemolysis, inflammation, hepatic dysfunction, renal and lipid metabolism. Methods: We evaluated a total of 125 SCD steady-state patients, 22 SCD in crisis patients, and 32 healthy individuals age- and sex-matched with patients groups. Hematological analyses were performed by automatic cell counter, and hemoglobin profile by HPLC. Biochemistry analyses of inflammatory and infection markers, as well as lipid, hepatic, and kidney metabolism markers were investigated by immunochemistry assays. Plasma concentration of total free heme was measured by QuantiChrom Heme Assay Kit. Results: SCD patients groups (steady state and crisis) had higher heme concentration when compared to healthy individuals (p < 0.0001). However, significant difference of heme level was not finding in the comparison between SCD in steady state and SCD crisis patients groups. Biomarkers analyses of steady-state SCD patients showed negative correlation between heme levels and: red blood cell (r = -0.36, p<0.0001); hematocrit (r = -0.38, p <0.0001); hemoglobin (r = -0.34, p <0.0001); and HDL-C (r = -0.42, p <0.0001). Heme level showed positive correlation with: platelets (r = 0.35, p <0.0001); lactic dehidrogenase (r = 0.40, p <0.0001); reticulocytes count (r = 0.19, p =0.04); monocytes count (r = 0.36, p <0.0001); HbS concentration (r = 0.54, p <0.0001); total proteins (r = 0.22, p =0.01); AST (r = 0.41, p <0.0001); ALT (r = 0.18, p= 0.04); serum iron (r =0.21, p =0.03); total cholesterol (r = 0.23, p =0.01); LDL-C (r = 0.22, p= 0.02); VLDL-C (r = 0.65, p <0.0001); and triglycerides (r = 0.63, p <0.0001). In steady state SCD patients there was no difference of clinical manifestations history and heme levels. Conclusions: The finding of similar heme concentration between steady state and crisis SCD patients may be explained by the hyperhemolysis phenomenon, showing that even in steady-state, these patients continue to have hemolysis and generate heme and reactive oxygen species. It was also shown that high concentration of free heme increases hemolytic and inflammatory biomarkers, such as LDH, bilirubin's, reticulocytes count, and lipids, contributing to a severe clinical modulation of SCD. Disclosures No relevant conflicts of interest to declare.
Acute colonic pseudobstruction (Ogilvie's syndrome) is a severe, life threatening condition characterized by acute colonic distension without evidence, or mechanical obstructive factor. Prompt detection results in an early colonoscopy treatment, which results in better prognosis. We report the case of a 57 year old female patient, with a previously diagnosed follicular lymphoma which presented with severe abdominal distention, impairing adequate thoracic expansion. The abdominal CT performed showed a significant dilatation of the cecum (13.27cm), with no mechanical obstruction. A decompressive colonoscopy was performed, with immediate clinical response.
Background: Sickle cell disease (SCD) is a group of inherited anemia characterized by heterogeneous clinical outcome, including hemolysis, chronic inflammation, and vaso-occlusive/painful crisis. Aims: We evaluated inflammatory and anti-inflammatory mediators, such as TNFα, IL-10, IL-12, IL-1β, IL-6, and IL-8, TGF-beta, tissue inhibitor of metalloproteinase (TIMP1), matrix metalloproteinase 9 (MMP9), heme, and leukotriene B4 (LTB4), and prostaglandin E2 (PGE2), the last two are products of the eicosanoid synthesis pathways, in SCD patients (in steady-state and in crisis-state) and healthy controls. For the same groups, in order to establish biomarkers of crisis and steady-state, we also investigated association among inflammatory/anti-inflammatory mediators and markers of hemolysis, inflammation, hepatic dysfunction, renal and lipid metabolism. Methods. We assessed 129 SCD steady-state patients (SP), 23 SCD in crisis patients (CP), and 67 healthy individuals (HC) age- and sex-matched with patients groups. Hematological analyzes were performed by automatic cell counter and hemoglobin profile by HPLC. Biochemistry analyses of inflammation and infection markers, as well as lipid, hepatic, and kidney metabolism markers were investigated by immunochemistry assays. Plasma levels of TNFα, IL-10, IL-12, IL-1β, IL-6 and IL-8 were measured using Cytometric Bead Array (CBA) according to the manufacturer's protocol. Plasma concentration of total heme was measured by QuantiChrom Heme Assay Kit. PGE2, LTB4, TGF-beta, TIMP1 and MMP9 levels were estimated in plasma samples and supernatants by ELISA, according to the manufacturer's instructions. Results . Steady-state SCD patients had the highest values of LTB4, PGE2, TIMP1, MMP9, IL-8, and IL-12 concentration compared with CP and HC groups (p < 0.0001). However, crisis-state SCD patients had the highest values of IL-1β, IL-6, IL-10, TNFα compared to HC and SP groups, and had a the lowest levels of LTB4, PGE2,TGF-β, MMP9, IL-8 and IL-12 levels (p < 0.0001 for both analysis). Significant difference of heme levels was not finding among the three groups. The ROC curve showed that LTB4, PGE2 and TGF- β are important markers related to steady state and IL-1β, IL-6, and TNFα are markers of crisis in SCD. Conclusions: The finding of difference in inflammatory markers level in steady state and crisis SCD patients suggest that these markers can be used to monitoring patients and to predict crisis events. The finding of similar heme concentration between steady-state and crisis-state SCD patients may be explained by the hyperhemolysis phenomenon, showing that even in steady-state, these patients continuous to have hemolysis and, consequently, continuous to generate heme and reactive oxygen species. Disclosures No relevant conflicts of interest to declare.
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