Clinical and Laboratory Predictors for Renal Damage in Sickle Cell Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3252-3252
Author(s):  
Santosh L Saraf ◽  
Robert Molokie ◽  
Johara Hassan ◽  
Michel Gowhari ◽  
James Lash ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Reticulocyte Count ◽  
Female Gender ◽  
P Value ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Indirect Bilirubin ◽  
Laboratory Variables

Abstract Abstract 3252 Renal failure is an independent marker for developing other forms of chronic organ damage and for early mortality in sickle cell disease (SCD). We conducted a retrospective, cross-sectional chart review of 292 adults with SCD (type SS or S-beta thal) treated at the University of Illinois Medical Center to assess the prevalence and factors related to kidney damage. Data was recorded from a clinic visit at least four weeks from a vaso-occlusive pain episode or red blood cell transfusion. The glomerular filtration rate (GFR) was calculated using the modification of diet in renal disease formula. Hemoglobinuria was defined by dipstick urinalysis showing trace, small, or moderate blood and <2 RBC/high power field. Urine albumin to creatinine ratios of 30 to 300 mg/g and >300 mg/g were categorized as microalbuminuria and macroalbuminuria, respectively. The median age was 33 years and 46% of patients were on hydroxyurea. We observed microalbuminuria in 41%, macroalbuminuria in 20%, hemoglobinuria in 41% and GFR <90 mL/min in 20% of adults with SCD. Univariate associations with GFR <90 mL/min are summarized in Table 1. By logistic regression, macroalbuminuria (OR 7.5, 95% CI: 2.5–22.2; p<0.0001) and age (OR 1.11, 95% CI: 1.06–1.16; p <0.0001) were independent predictors of GFR <90 mL/min (r2 = 0.23). Given the strong correlation of macroalbuminuria with GFR <90 mL/min, we explored factors related to degree of albuminuria. Univariate associations with degree of albuminuria are shown in Table 2. Logistic regression showed that independent predictors for macroalbuminuria were the presence of hemoglobinuria (OR 93.7, 95% CI: 15.2–576.5; p<0.0001) and age (OR 1.07, 95% CI: 1.01–1.14; p=0.03) (r2=0.28, p<0.0001). We further explored predictors of hemoglobinuria given its independent association with macroalbuminuria. By logistic regression, the strongest predictor of hemoglobinuria was the natural log LDH (OR 32.4; 95% CI: 8.4–124.9; p<0.0001) (r2=0.22), but other markers of hemolysis including higher absolute reticulocyte count, greater indirect bilirubin concentration and lower hemoglobin concentration were also associated with hemoglobinuria in univariate analyses. In summary, increasing age and macroalbuminuria were independent factors associated with GFR < 90mL/min in this cohort of adults with SCD, and intravascular hemolysis as reflected in hemoglobin-positive urine dipstick with negative microscopy was associated with macroalbuminuria. Further research is needed to determine if measures to decrease intravascular hemolysis and to prevent the development of macroalbuminuria can preserve renal function in patients with SCD. Investigation is also needed to identify genomic and genetic markers that put patients at risk for kidney disease and might serve as targets for preventive and therapeutic interventions. Table 1: Correlation of GFR to clinical and laboratory variables. Variable N >90 N <90 p-value Age (years) 234 30 (25–39) 58 45 (37–54) <0.0001 Female gender 234 141 (60%) 58 38 (65%) 0.63 MAP 231 86 (90–93) 58 91 (86–98) <0.0001 HU therapy 110 48 (44%) 30 16 (53%) 0.35 Hemoglobin (g/dL) 234 8.9 (7.9–10) 58 8.1 (7.4–8.9) <0.0001 LDH (u/L) 146 309 (235–425) 41 375 (251–481) 0.11 Absolute Reticulocyte Count (×103/μL) 111 332 (234–444) 29 302 (197–368) 0.001 Hgb F (%) 218 5.5 (2.9–9.8) 52 5.5 (2.5–9.8) 0.98 Albuminuria: Microalbuminuria Macroalbuminuria 112 46 (41%) 30 11 (36.7%) 0.001 15 (13%) 13 (43.4%) Table 2: Correlation of Albuminuria to clinical and laboratory variables. Variable N Normal N Micro-albuminuria N Macro-albuminuria p-value Age (years) 57 32 (26–42) 58 38 (28–48) 28 35 (27–45) 0.20 Female gender 57 43 (75%) 58 34 (59%) 28 18 (64%) 0.16 MAP (mmHg) 56 86 (80–97) 58 88 (84–92) 28 91 (84–98) 0.24 HU therapy 56 24 (42.9%) 57 24 (42.1%) 28 17 (60.7%) 0.22 Hemoglobin (g/dL) 57 8.9 (8.1–10.3) 58 8.1 (7.5–9.4) 28 8.5 (6.9–9.4) 0.008 LDH (u/L) 54 270 (212–358) 49 363 (251–434) 27 377 (355–488) <0.0001 Indirect bilirubin (mg/dL) 56 1.7 (1.2–2.5) 57 2.4 (1.4–3.3) 28 2.0 (1.3–4.3) 0.03 Absolute reticulocyte count (×103/μL) 57 256 (213–399) 56 332 (243–448) 28 369 (276–466) 0.06 Hgb F (%) 52 6.6 (2.7–9.7) 56 5.1 (2.8–11.7) 26 7.8 (3.7–13) 0.54 Hemoglobinuria 53 3 (5.7%) 54 29 (53.7%) 26 22 (84.6%) <0.0001 Disclosures: No relevant conflicts of interest to declare.

Predictors of Adverse Outcomes in Hospitalized Adult Patients with Sickle Cell Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3197-3197
Author(s):  
Fahd Rahman ◽  
Roy N. Gay ◽  
Samir K. Ballas ◽  
Juan C. Zubieta ◽  
Zekarias Berhane ◽  
...  
Keyword(s):  
At Risk ◽  
Logistic Regression ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Acute Pain ◽  
Reticulocyte Count ◽  
Laboratory Data ◽  
Adverse Outcomes ◽  
Acute Chest Syndrome ◽  
Cell Disease

Abstract The identification of patients with sickle cell disease at risk of serious complications at the time of hospital admission can help stratify patients who will need aggressive management. We identified predictors associated with adverse outcomes such as frequent hospitalizations, acute pain crises and acute chest syndromes. To that end, we retrospectively reviewed medical records of 265 adult sickle cell disease patients, hospitalized between 1/1/98 and 2/3/05 at Mercy Catholic Medical Center, with complete clinical and laboratory data. 195/73.6% had HbSS and the rest had HbSC, HbSβ-thal0,HbS-βthal+or HbSOarab disease. 59 variables were considered including demographic, hematological, biochemical, clinical and treatment data. Logistic regression models were used to obtain associations between variables, and to adjust for confounding effects. Analysis showed that adverse events during admission included acute pain crises in 249/94%, acute chest syndromes in 25/9.4% and strokes in 5/1.9% patients. Other outcomes were a greater than 2 hospitalizations per year 82/31.9%, more than 2 pain crises per year 145/54.7%, transfusion required during admission 72/27.2%, length of hospital stay more than 5 days 105/39.6% and death during hospitalization 13/4.9%. Multivariate logistic regression analysis revealed 21 factors with statistically significant associations. A reticulocyte count greater than 1.5 (OR 3.98, CI 1.48–10.69, P.006) and employment status (OR .31, CI .13-.75, P.009) were associated with more admissions per year. History of acute chest syndrome (OR 5.33, CI 1.7–16.77, P.004), reticulocyte count greater than 1.5 (OR 3.46, CI .91–13.11, P.067) and care provided by a nonhematologist (OR 5.04, CI 1.7–14.95, P.0035) were linked with more pain crises per year. Pain crises during admission were associated with HbSS disease (OR 9.31, CI 2.17–39.9, P.01) and out patient folate therapy(OR 6.23, CI 1.45–26.84, P.003). Patients with leukocytosis (OR 3.41, CI 1.2–9.67, P.02) and a higher serum glucose level (OR 7.54, CI 2.6–21.86, P.0002) were linked to more acute chest syndromes. Females (OR .1, CI .03–.37, P.0004) were at lower risk of having acute chest syndromes. Outpatient folate therapy (OR .07, CI .007–.69, P.02) was associated with lower numbers of acute neurological events. Patients with initial hemoglobin levels less than 7 g/dL (OR 1.99, CI 1–4, P.0007) and prolonged hospitalization (OR 7.06, CI 3.63–13.74, P.0001) frequently required transfusions. Variant diseases (OR .28, CI .13–.58, P.05) required fewer transfusions. Deaths during hospitalization were lower with folate therapy (OR .18, CI .05–.63, P.007) and a transfusion requirement during admission (OR 5.07, CI 1.45–17.64, P.01) predicted more deaths. HbSS patients (OR 2.52, CI 1.1–5.8, P.03), substance abusers (OR 2.93, CI 1.21–7.08, P.01), those requiring antihistamines during admission (OR 3.33, CI 1.38–8.03, P.007), or requiring more than 2 hospitalizations per year (OR 2.62, CI 1.26–5.43, P.009) had hospital stays longer than 5 days while in females odds were low for this outcome (OR .30, CI .15–.59, P.0005). In conclusion, simple tools like a complete history, physical examination, demographic and laboratory data can help clinicians and health care providers to gauge severity of the illness and deliver tailored management protocols targeting these “at risk” sickle cell disease patients.

Elevated Tricuspid Regurgitant Jet Velocity In Lebanese Patients With Sickle Cell Disease Is Associated With Severe Disease and Is Clustered In Families

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4684-4684
Author(s):  
Rouba Abdennour ◽  
Mariam Arabi ◽  
Paul Nietert ◽  
Sarah Keyrouz ◽  
Ruby Khoury ◽  
...  
Keyword(s):  
Young Adults ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Rate Ratio ◽  
Reticulocyte Count ◽  
Severe Disease ◽  
P Value ◽  
Cell Disease ◽  
Familial Clustering ◽  
The Mean

Introduction Pulmonary hypertension (PHT) is a known complication of sickle cell disease (SCD), and it is indirectly assessed by measurement of the tricuspid regurgitant jet velocity (TRV). Despite the fact that PHT was found to be associated with early mortality in adults SCD patients, the association between elevated TRV and SCD severity and mortality is still controversial particularly in children and adolescents. The objective of this study was to investigate the relationship between elevated TRV and parameters of disease severity in children, adolescents and young adults with SCD. Methods The study is a retrospective review of medical records of patients with SCD followed at the comprehensive sickle cell clinic at the American University of Beirut Medical Center between April 2002 and January 2012. These include 115 patients with homozygous hemoglobin S disease, 8 with sickle β0-thalassemia, and 24 with sickle β+-thalassemia who have had at least one echocardiogram done as part of their routine medical care. All echocardiograms were done at steady state, at least four weeks after the last vasoocclusive crisis (VOC) or acute chest syndrome (ACS). Elevated TRV was defined as peak TRV of 2.5 meters per second or higher. Disease severity was assessed by comparing hemolysis biomarkers, rate of transfusions, VOCs and ACS and other SCD complications. In patients with sequential echocardiograms, changes in hydroxyurea (HU) doses were examined against TRV variation. Results 147 patients were studied over a mean number of 3.77 ± 1.96 years. The mean age was 15.07 ± 8.62 years, ranging from 18 to 43.4 years, with 66% being below 18 years of age. Elevated TRV was found in 57 patients (38.8%). T-tests and chi-square tests did not show any statistically significant differences between the patients with normal and elevated TRV with respect to age, gender, SCD subtype, time of follow-up, presence of stroke, AVN, ulcers and splenectomy. In addition, hemoglobin (mean=9.43±1.46 in normal TRV group versus 9.20±1.19 in high TRV, p=0.309) mean corpuscular volume (MCV, mean=93.04±16.96 vs. 96.56±15.03, p=0.203), reticulocyte count (mean= 9.51 ± 4.81 vs 9.97±5.55, p=0.596), bilirubin (indirect bilirubin mean=1.40±1.28 vs. 1.44±1.04, p=0.883) and lactate dehydrogenase (LDH, mean=423.20±192.00 vs. 451.40±399.40, p=0.398) did not show any significant differences between the two groups. Among patients with elevated TRV, 71.9% were on HU at a mean dose of 16.27 mg/kg/day compared to 70% of patients with low TRV who were on a mean HU dose of 15.13 mg/kg/day. HU was started in both groups for indications including pain crises, ACS and low hemoglobin but not TRV alone. Initially markers of hemolysis including MCV, reticulocyte count, bilirubin and LDH were significantly higher and hemoglobin lower in patients with elevated TRV, but these differences between the two groups were no longer evident after the dose of HU was optimized. In the 99 patients with 2 or more echocardiograms, no trend in TRV variation was observed after HU dose adjustment and sequential TRV readings. The mean transfusion rate per patient did not differ between the two groups. However, RBC alloimmunization was found in 6.2% of patients with normal TRV compared to 15% of patients with elevated TRV. Results of the Poisson models demonstrated that the VOC rate was 1.4 times higher among subjects with TRV ≥ 2.5 compared to subjects with TRV < 2.5 (rate ratio = 1.4; 95% CI = 1.04 to 2.02; p=0.029). Additionally, ACS rate was almost 3 times higher among subjects with high TRV (rate ratio = 2.8; 95% CI = 1.3 to 6.2; p=0.01). No deaths were reported in either study groups. Fisher's exact test and the generalized linear mixed model (GLMM) both indicated the presence of familial clustering of elevated TRV (Fisher's p-value: 0.009; GLMM p-value: 0.026). Conclusion The overall prevalence of elevated TRV in our study population was 38.8%. Despite improvement in hemolyis after introducing and optimizing hydroxyurea doses, patients with elevated TRV still had more severe disease as defined by higher rates of VOC, ACS and alloimmunization. Familial clustering of elevated TRV was observed in our highly consanguineous population. These findings suggest that elevated TRV is a marker that defines patients with more severe SCD even among children and young adults. Disclosures: No relevant conflicts of interest to declare.

Hypocholesterolemia in a Large Sickle Cell Cohort: Correlations of Serum Lipids to Markers of Intravascular Hemolysis and Vascular Dysfunction

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 123-123
Author(s):  
Suzana M. Zorca ◽  
Lita A. Freeman ◽  
Patricia L. Littel ◽  
Gregory J. Kato
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Total Bilirubin ◽  
Reticulocyte Count ◽  
Vascular Dysfunction ◽  
Healthy Controls ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Cholesterol Levels ◽  
The Mean

Abstract Background: Hypocholesterolemia in sickle cell disease (SCD) has been documented in small cohorts from Nigeria, Cameron, Iran and the United States. Although not uniformly consistent, these studies found decreased total plasma cholesterol levels, HDL- cholesterol (HDL-C) and LDL-cholesterol (LDL-C), when compared to healthy controls. Consistent with the low levels of LDL-C, atherosclerosis is largely absent in SCD patients. However, vascular dysfunction is prevalent, and higher-than-average triglyceride (TG) levels, a known risk factor for vascular diseases, have also been reported in SCD populations. Methods: In a large SCD cohort, consisting of 405 SCD patients with normal and mildto- significantly elevated pulmonary artery pressures (tricuspid regurgitant jet velocities (TRVs) ranging from 1 to 4.9) as well as 32 healthy African American controls, we determined mean serum lipid levels for total cholesterol, HDL-C, LDL-C and TG. We also determined apolipoprotein levels, ApoA-I, ApoB and the ratio ApoA-I/ApoB. We then investigated the correlations between plasma serum lipids and apolipoproteins against a battery of markers of intravascular hemolysis and vascular dysfunction. Results: In our large cohort, we observe significantly lower mean total cholesterol levels in SCD patients versus healthy controls (135.2 and 187.5 mg/dL, respectively, p&lt;0.001). Total serum cholesterol was negatively correlated to markers of intravascular hemolysis (absolute reticulocyte count, p&lt;0.0001; total bilirubin, p&lt;0.0001, indirect bilirubin, p&lt;0.0001), and positively associated with hemoglobin and hematocrit (p=0.0036 and p=0.0028, respectively). Mean HDL-C levels were statistically significantly lower in the SCD cohort versus healthy controls (41.27 and 58.91, respectively, p&lt;0.0001), and were also negatively correlated to absolute reticulocyte count (p&lt; 0.0001), total bilirubin (p&lt;0.0001) as well as to LDH, another well-known marker of intravascular hemolysis (p&lt;0.0001). Mean LDL-C levels were significantly lower in SCD patients than in control subjects (78.22 and 117.1 mg/dL, respectively, p&lt;0.0001), and were negatively correlated to reticulocyte count (p=0.0002), and total bilirubin (p= 0.0025). In contrast, mean triglyceride levels were significantly higher in the SCD cohort than in healthy subjects (123.2 vs. 76.42 mg/dL respectively, p&lt;0.0001), and were inversely correlated to hemoglobin (p= 0.0005) and hematocrit (p= 0.0003). TGs were also significantly positively correlated to markers of hemolysis: plasma hemoglobin (p= 0.0004), LDH (p= 0.0005), and with arginase (p=0.003), ornithine (p&lt; 0.0001), and SE selectin (p= 0.0386). Moreover, when the SCD cohort was divided among low-TRV (&lt;2.5), moderate-TRV (2.5–2.9) or high-TRV (&gt;2.9) cohorts, the mean plasma TG levels were significantly different between the low and high TRV groups. Specifically, for low-TRV patients (TRV&lt;2.5, n=197), the mean plasma TG level was 110.5 mg/dL (95% confidence interval 102.5–118.6, median 102.0); for moderate-TRV patients (TRV=2.5–2.9, n=103) the mean TG level did not differ significantly from the low-TRV group (TG=115.3 mg/dL, 95% CI 104.6–126.1; median 105.0); however, for high TRV patients (TRV&gt;2.9, n = 58), the TG mean was significantly higher (153.4, 95% CI 131.4–175.5, median=136.0). Interestingly, ApoA-I levels were also low in SCD patients, and there was a trend towards lower ApoA-I levels in the higher TRV patient groups, but this trend did not achieve statistical significance. Lastly, ApoA-I levels were significantly positively correlated with NTProBNP, a marker of pulmonary hypertension (p= 0.0026). Conclusions: To our knowledge, this constitutes the first evidence that hypocholesterolemia in sickle cell disease is correlated with markers of intravascular hemolysis and vascular dysfunction. Further study is needed to explore the mechanistic basis for these correlations; however, one possibility is that the fatty acids carried by triglycerides may become oxidized in SCD patients with hemolytic oxidative stress and serve as signaling molecules, or alternatively, hemolytic oxidative stress may coordinately regulate these pathways. Our findings provide a link between plasma lipids, particularly triglyceride levels, and vascular dysfunction in sickle cell disease.

European Ancestry Is Associated with Acute Chest Syndrome in Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4051-4051
Author(s):  
Ken Batai ◽  
Taimur Abbasi ◽  
Maggie Parker ◽  
Xu Zhang ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Phenotypic Variability ◽  
European Ancestry ◽  
Ancestral Population ◽  
Acute Chest Syndrome ◽  
P Value ◽  
Cell Disease

Abstract Background: Acute chest syndrome (ACS) is a major cause of morbidity and mortality in patients with sickle cell disease (SCD). The elucidation of genetic modifiers and mechanisms responsible for the phenotypic variability in ACS and SCD would have important clinical implications such as the identification of individuals at high risk for ACS complications and the potential for use of individualized preventive and therapeutic strategies that could ultimately improve outcomes for patients with SCD. We hypothesize that the development of ACS is significantly influenced by ancestry. Methods: Autosomal SNPs were genotyped with the Affymetrix PanAFR array in a University of Illinois cohort and with the Illumina 6.0 platform in the NIH Walk-PHaSST cohort. We merged the two GWAS datasets and there were 100,079 SNPs available after removing SNPs with > 2 alleles and Hardy-Weinberg Equilibrium (HWE) P<0.001. From HapMap Phase 3 genotype data, we selected 5,000 SNPs that exhibit large frequency differences between YRI and CEU (P < 1.57 x 10-29). Five hundred and fifteen of these SNPs were identified in the 100,079 SNPs genotyped in both GWAS arrays. After removing 152 SNPs with FST < 0.3 and 9 SNPs linked to other SNPs with r2>0.2, the total number of SNPs available for ancestry estimates was 354. Genetic ancestry was estimated using HapMap YRI and CEU genotypes as ancestral population (K=2) using STRUCTUR 2.1. We ran STRUCTURE under the admixture model using prior population information and assuming allele frequencies among populations, with a burn-in length of 30,000 for 70,000 repetitions. Logistic regression was used to examine the association between European ancestry (EA) and Acute Chest Syndrome. Age, gender, hemoglobin genotype (HbSS/HbSβ0 vs. others), and use of hydroxyurea were additionally considered during modeling. Results: Seven hundred and thirty patients (UIC= 233, Walk-PHaSST = 497) were included in the analysis (Table 1). In binary logistic regression analysis adjusting for age, gender, Hb genotypes (severe vs. mild) and hydroxyurea use, EA was associated with and increase in ACS risk in both cohorts and when the cohorts where combined (UIC P=0.02, Walk-PHaSST P=0.001, combined P<0.001). A similar trend was observed when degree of EA was stratified (Table 2). Summary: Population structure and admixture influence the risk of ACS. European ancestry is associated with an increased ACS risk. Abstract 4051. Table 1. Characteristics of study subjects UIC Walk-PHaSST Pooled ACS no-ACS ACS no-ACS ACS no-ACS Number 195 38 299 198 494 236 Mean Age (SD) 36.1 (12.1) 40.4 (12.5)a 38 (13.4) 36 (12.7) 37 (12.9) 37 (12.7) No. females (%) 113 (58%) 23 (61%) 163 (54%) 109 (55%) 276 (56%) 132 (56%)a HbSS /HbSβ0 (%) 153 (79%) 21 (55%)b 242 (81.5%) 136 (70.8%)b 395 (80.4%) 157 (68.2%)b % European Ancestry (SD) 22 (9.9) 20 (7.4) 20 (13.5) 17 (12.5)a 21 (12.3) 18 (11.9) % West African Ancestry (SD) 78 (9.9) 80 (7.4) 80 (13.5) 83 (12.5)a 79 (12.3) 82 (11.9) aP<0.05 comparing ACS to non-ACS within site bP<0.002 comparing ACS to non-ACS within site Table 2. European Ancestry Strata and ACS Risk UIC Walk-PHaSST Pooled OR (95% CI) P-value OR (95% CI) P-value OR (95% CI) P-value Ancestry Strata Less than 14.3% Ref. Ref. Ref. 14.3% to 23.2% 0.59 (1.2 - 21) 0.339 1.05 (0.7 - 1.6) 0.831 1.28 (0.9 - 1.9) 0.206 Greater than 23.2% 1.21 (0.4 - 3.9) 0.741 1.65 (1.1 - 2.6) 0.028 2.03 (1.4 - 3.0) 0.005 Disclosures No relevant conflicts of interest to declare.

scholarly journals Vitamin D and Nonskeletal Complications among Egyptian Sickle Cell Disease Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Mona Hamdy ◽  
Niveen Salama ◽  
Ghada Maher ◽  
Amira Elrefaee
Keyword(s):  
Vitamin D ◽  
Sickle Cell Disease ◽  
Vitamin D Deficiency ◽  
Sickle Cell ◽  
Standard Of Care ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Disease ◽  
P Values ◽  
Indirect Bilirubin ◽  
Deficient Group

Lower levels of vitamin D have been documented in many patients with sickle cell disease (SCD), but data are still inconclusive regarding the association between vitamin D deficiency (VDD) and the occurrence or the severity of various SCD complications. Our study aimed to detect the prevalence of vitamin D deficiency among Egyptian patients with SCD and to associate it with the clinical course of the disease. We measured the level of 25-hydroxy vitamin D in 140 children (age from 4.3 to 15.5years), 80 patients with SCD and 60 controls using enzyme-linked immunosorbent assay. Vitamin D was deficient in 60% of SCD compared to 26.7% of controls. Severe VDD was significantly higher in SCD patients than controls. Patients were divided into 2 groups; Normal group (32 patients) and Deficient group (48 patients). There were statistically significant differences between the 2 groups regarding their age, height percentile, the presence of clinical jaundice, and osseous changes (P values 0.043, 0.024, 0.001, and 0.015, respectively). Hemoglobin and hematocrit values were significantly lower in Deficient group (P values 0.022 and 0.004, respectively) while the levels of aspartate aminotransferase, lactate dehydrogenase, and total and indirect bilirubin were significantly higher in the same group (P values 0.006, 0.001, 0.038, and 0.016, respectively). The frequency of blood transfusions, hospitalization, and vasoocclusive crisis previous year as well as the history of bone fracture and recurrent infections proved to be significantly higher in Deficient group. These findings suggest that VDD may play a role in the pathogenesis of hemolysis and other complication of SCD. Vitamin D monitoring and supplementation in patients with SCD should be implemented as a standard of care to potentially improve health outcomes in these affected patients.

scholarly journals Predictors of musculoskeletal manifestations in paediatric patients presenting with sickle cell disease at a tertiary teaching hospital in Lusaka, Zambia

2020 ◽  
Vol 1 (6) ◽  
pp. 175-181
Author(s):  
Raymond Mpanjilwa Musowoya ◽  
Patrick Kaonga ◽  
Alick Bwanga ◽  
Catherine Chunda-Lyoka ◽  
Christopher Lavy ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Teaching Hospital ◽  
Clinical Manifestations ◽  
Classification Systems ◽  
University Teaching ◽  
Cell Disease ◽  
Tertiary Teaching ◽  
Musculoskeletal Manifestations

Aims Sickle cell disease (SCD) is an autosomal recessive inherited condition that presents with a number of clinical manifestations that include musculoskeletal manifestations (MM). MM may present differently in different individuals and settings and the predictors are not well known. Herein, we aimed at determining the predictors of MM in patients with SCD at the University Teaching Hospital, Lusaka, Zambia. Methods An unmatched case-control study was conducted between January and May 2019 in children below the age of 16 years. In all, 57 cases and 114 controls were obtained by systematic sampling method. A structured questionnaire was used to collect data. The different MM were identified, staged, and classified according to the Standard Orthopaedic Classification Systems using radiological and laboratory investigations. The data was entered in Epidata version 3.1 and exported to STATA 15 for analysis. Multiple logistic regression was used to determine predictors and predictive margins were used to determine the probability of MM. Results The cases were older median age 9.5 (interquartile range (IQR) 7 to 12) years compared to controls 7 (IQR 4 to 11) years; p = 0.003. After multivariate logistic regression, increase in age (adjusted odds ratio (AOR) = 1.2, 95% confidence interval (CI) 1.04 to 1.45; p = 0.043), increase in the frequency of vaso-occlusive crisis (VOC) (AOR = 1.3, 95% CI 1.09 to 1.52; p = 0.009) and increase in percentage of haemoglobin S (HbS) (AOR = 1.18, 95% CI 1.09 to 1.29; p < 0.001) were significant predictors of MM. Predictive margins showed that for a 16-year-old the average probability of having MM would be 51 percentage points higher than that of a two-year-old. Conclusion Increase in age, frequency of VOC, and an increase in the percentage of HbS were significant predictors of MM. These predictors maybe useful to clinicians in determining children who are at risk. Cite this article: Bone Joint Open 2020;1-6:175–181.

scholarly journals 3458 Temporal Trends and Outcomes of Opioid Abuse among Adolescents & Young Adult Sickle Cell Disease Patients

2019 ◽  
Vol 3 (s1) ◽  
pp. 54-55
Author(s):  
Nnaemeka E Onyeakusi ◽  
Adebamike Oshunbade ◽  
Fahad Mukhtar ◽  
Adeyinka Adejumo ◽  
Semiu Gbadamosi ◽  
...  
Keyword(s):  
Young Adults ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Temporal Trends ◽  
Opioid Abuse ◽  
P Value ◽  
Total Charge ◽  
Inpatient Mortality ◽  
Cell Disease ◽  
Sickle Cell Crisis

OBJECTIVES/SPECIFIC AIMS: In this study, we aim to describe temporal trends in opioid abuse among adolescents and 11-21years and young adults 22-35years with Sickle cell disease hospitalized for sickle cell crisis. We also aim to evaluate clinical and healthcare utilization outcomes of opioid abuse in the same population. In addition, we hope to assess for difference in effect by age category. METHODS/STUDY POPULATION: Our study is a cross-sectional study of data secondarily sourced from the 2007-2014 National Inpatient Sample(NIS), a component of the Healthcare Utilization Project (HCUP). Variables were identified using ICD-9-CM codes. We selected inpatient stays for patients aged 11-35 years admitted for sickle cell crisis. Opioid abuse was the primary outcome of interest. Secondary outcomes were inpatient mortality, total charge, length of stay and select clinical outcomes. We analyzed our data for trends and outcomes. We performed trend analysis of prevalence rates between 2007-2014 by age categories. Propensity-Matched Score regression models were deployed to assess for associations between opioid abuse and outcomes while adjusting for relevant covariates. Sub-group analysis of opioid abuse by age was assessed for outcomes of interest. Trend analysis was performed on Joinpoint Software v4.6.0, (National Cancer Institute, NIH, Bethesda, MD). Outcome analysis was performed on SAS v9.4 (SAS Institute, Cary, NC). Statistical significance was set at 95% and p-value of 0.05, two-tailed. RESULTS/ANTICIPATED RESULTS: Of 86,827 inpatients admitted for sickle cell crisis, 2,363 (2.73%) had a diagnosis of opioid abuse while 84,464 (97.27%)did not abuse opioids. 27,004 (31.01%) of admitted patients were 11-21 years while 59,823 (68.99%) were 21-35 years. We found statistically significant APCs (Annual Percentage Change) showing increasing trends in both age categories for years under review, (18.47% [95% CI 15.39-21.63]; p-value <0.001 in young adults vs. 10.31% [95% CI 3.58-17.49]; p-value 0.009 in adolescents). The difference in APCs between both age categories were also significant (−8.16% [95% CI [−14.26-2.05]; p-value 0.009). There were no parallelism or coincidence in the trend lines. Opioid abuse was found to be associated with significantly longer length of stay (7.74 vs 6.05 days), higher total charge ($40,797 vs $32,164), (aOR 1.44; 95% CI [1.19-1.75]) seizures, sepsis (aOR 1.62; 95% CI [1.35-1.94]) and pulmonary hypertension (aOR 1.36; 95% CI [1.12-1.66]). No significant association was found for inpatient mortality, transfusion, cardiac dysrhythmias, pulmonary embolism and acute kidney injury. Significant interaction existed between opioid abuse and age for total charge (for $41,869 vs $29,371 among adolescents & $40,632 vs $32,550 among young adults; interaction p-value 0.03). DISCUSSION/SIGNIFICANCE OF IMPACT: Trends show a significant increase in the prevalence of opioid abuse among adolescents and an increasingly higher prevalence when adolescents transition to young adults. Opioid abuse among sickle cell patients is associated with significant poor healthcare resource utilization and clinical outcomes. Public health interventions to prevent worsening opioid abuse prevalence are expected to improve patient outcomes.

Polymorphisms in Inflammatory Genes Modulate the Occurrence of Clinical Complications in Patients with Sickle Cell Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4825-4825
Author(s):  
Karina Tozatto-Maio ◽  
Robert Girot ◽  
Indou Deme Ly ◽  
Vanderson Rocha ◽  
Ana Cristina Silva Pinto ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
African Descent ◽  
Additive Model ◽  
Sub Saharan Africa ◽  
Leg Ulcers ◽  
Cell Disease ◽  
1000 Genomes ◽  
Clinical Complications

Background: Patients (pts) with sickle cell disease (SCD) show a high phenotype variability that is not fully understood. Because inflammation plays a major role in SCD pathophysiology, we hypothesized that single nucleotide polymorphisms (SNPs) in genes of innate and adaptative inflammatory response modulate the occurrence of SCD complications. Objective: to establish associations between SNPs and clinical complications in pts with SCD. Methods: Case-control retrospective study; 500 pts were included, followed at Senegal (n=56), Brazil (n=230) and France (n=214). We analyzed the effect of 20 SNPs in 6 clinical complications: acute chest syndrome (ACS), stroke, leg ulcers, cholelithiasis, osteonecrosis and retinopathy. Using TaqMan 5'-nuclease assay, we genotyped SNPs in genes encoding Toll-like receptor (TLR) 1 (rs4833095), 2 (rs4308099, rs4308100, rs4696480), 6 (rs5743810), 10 (rs11466653, rs11096957), natural killer (NK) group 2 member D (NKG2D) receptor (rs1982536, rs2617160, rs2617169, rs2617170, rs2617171, rs1049174, rs2246809, rs2255336), human leukocyte antigen (HLA)-G (rs9380142), HLA-E (rs2517523), major histocompatibility complex class I polypeptide-related sequence A (MICA, rs1051792) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) (rs5742909, rs231775). All SNPs had a call rate >90% and minimum allele frequency >1%. We performed analyses of correspondence for indicating associations between SNPs and number of clinical complications. Logistic regressions were used to identify associations between SNPs and each complication, using geographical origin, SCD genotype, rate of transfusions and gender for modeling adjustment; the significance was adjusted for multiple testing using false discovery rate. Comparisons of genotype frequencies with the population of African descent from 1000 genomes database were done by chi-square. Results: Pts were originally from Brazil (n=228), Sub-Saharan Africa (n=200), French West Indies (n=53), North Africa (n=7) and 12 unknown. SCD genotype (available n=498) was SS (n=402), SC (n=46), SB (n=42), SD or SE (n=4). 280 pts were female; median age was 32 years (range 0-69); 184 pts received at least 20 transfusions. 71 pts presented stroke, 200 had at least 1 episode of ACS, 69 had leg ulcers, 271 had cholelithiasis, 150 had retinopathy and 90 osteonecrosis. 97 pts did not present complications, 135 had 1 type of clinical complication, 134 had 2, 94 had 3, 34 had 4 and 6 had 5. 21 pts underwent hematopoietic stem cell transplantation. 11 pts died during follow-up, mostly from ACS and hemorrhagic stroke. Indication of association with number of complications: TLR2 rs4696480 TA, TLR2rs3804099 CC and HLA-Grs9380142 AA were associated with occurrence of 0-1 clinical complications, MICA rs1051792 AA/AG with up to 2 complications and NKG2D rs2617169 AA with 5 complications. Association between genotypes/haplotypes and each complication: no association was found between SNPs and stroke, ACS, leg ulcers and osteonecrosis. Rs9380142 was the only SNP significantly associated with cholelithiasis in the logistic regression additive model. The G allele increased the risk of cholelithiasis (AG x AA, OR 1.57, 95%CI 1.16-2.15; GGxAA, OR 2.47, 95%CI 1.34-4.64; P=0.02). For retinopathy, in the logistic regression additive model, the presence of the A allele decreased the risk of retinopathy for rs2246809 in pts of same origin (AAxGG: OR 0.22, 95%CI 0.09-0.50; AGxGG: OR 0.47, 95%CI 0.31-0.71; P=0.004), rs2617160 (ATxTT: OR 0.67, 95%CI 0.48-0.92; AAxTT: OR 0.45, 95%CI 0.23-0.84; P=0.04) and rs2617169 in pts of same SCD genotype (AAxTT: OR 0.33,95%CI 0.13-0.82; ATxTT: OR 0.58, 95%CI 0.36-0.91, P=0.049). No haplotype was associated with complications. The genotype distribution of SNPs rs4696480, rs3804099, rs1051792 and rs2617169 differed significantly from the population of African descent from the 1000 genomes database. Discussion: We have previously shown that TLR2 rs4696480 TA decreases occurrence of bacterial infections in SCD; in this study, TA is also associated with less complications. Also, HLA-G rs9380142 AA had less complications and cholelithiasis, and 3 SNPs in NKG2D modulated occurrence of retinopathy. TLR and NKG2D may be activated by heat shock proteins, released in ischemia-reperfusion injury that occurs in SCD. Our findings help to better understand the role of inflammation in phenotype heterogeneity in SCD. Disclosures No relevant conflicts of interest to declare.

Arginine Metabolite Profiling in Sickle Cell Disease: Abnormal Levels and Correlations with Pulmonary Hypertension, Desaturation, Hemolysis and Organ Dysfunction.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1205-1205
Author(s):  
Gregory J. Kato ◽  
Wang Zeneng ◽  
James G. Taylor ◽  
Roberto F. Machado ◽  
William C. Blackwelder ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Renal Dysfunction ◽  
Sickle Cell ◽  
Early Mortality ◽  
Systemic Hypertension ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Arginine Transport

Abstract Pulmonary arterial hypertension (PAH) in patients with sickle cell disease (SCD) is linked to intravascular hemolysis, renal dysfunction, systolic hypertension, cholestasis, and early mortality. Although the pathophysiology of PAH in SCD is multifactorial, one important and fundamental factor is impaired nitric oxide bioavailability. Severe intravascular hemolysis releases hemoglobin and arginase into blood plasma, leading to consumption of nitric oxide and its plasma precursor L-arginine, the obligate substrate for the nitric oxide synthases (NOS). In order to explore other potential alterations in the arginine pathway that might affect arginine bioavailability and nitric oxide production, we used high-performance liquid chromatography-tandem mass spectrometry to determine the plasma concentrations for several key metabolites that may affect NOS activity or arginine transport: asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), N-monomethyl-L-arginine (MMA), and N-ω-hydroxy-L-arginine (NOHA). Plasma levels of ADMA, SDMA and MMA are significantly higher in all forms of SCD than in healthy African American control subjects (Table 1). NOHA, the intermediate species in nitric oxide synthesis from L-arginine, is significantly lower in sickle-β-thalassemia (Sβ-thal) patients and homozygous SCD (SS). L-arginine levels are significantly lower in all forms of SCD, as previously reported. PAH as assessed by echocardiography screening was correlated to SDMA (r=0.30, p&lt;0.0001) and NOHA (r=0.23, p=0.002). Similar correlations were observed to NT-proBNP, another marker of PAH. Low oxygen saturations were linked to high levels of all four arginine metabolites. ADMA levels were elevated with severe hemolysis, and unexpectedly lower with renal dysfunction. Levels of SDMA and NOHA were significantly related to renal dysfunction (p&lt;0.01), with an additional link of NOHA to systemic hypertension (p&lt;0.001). In addition, Cox proportional hazard analysis showed a relationship of the arginine/SDMA ratio to early mortality (p&lt;0.001). In summary, levels of the endogenous NOS inhibitor ADMA are highly elevated in SCD and linked to hemolysis, and may contribute to hemolysis-associated endothelial dysfunction. The levels of SDMA, a competitive inhibitor of arginine transport and intracellular bioavailability, are also elevated and linked to PAH, desaturation, renal dysfunction and early mortality risk. The low levels of arginine and NOHA in SCD are consistent with low substrate availability for NOS, and may also limit NO production. The role of arginine metabolites in dysregulation of the arginine-nitric oxide axis and pulmonary hypertension in SCD merits further investigation. Table 1. Arginine Metabolites in Sickle Cell Disease compared to controls. Metabolite Control (n=29) SC (n=34) Sβ-thal (n=11) SS (n=130) Values indicate median values in μM. *p&lt;0.05; **p&lt;0.01; ***p&lt;0.001, Mann-Whitney test compared to controls. ADMA 0.31 0.82*** 0.92* 0.99*** SDMA 0.83 0.92* 1.03** 1.03*** MMA 0.13 0.15* 0.20** 0.18*** NOHA 2.50 2.23 2.15* 1.80** L-Arginine 78.3 51.5*** 41.6*** 45.5***

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