Heme Concentration As a Biomarker of Sickle Cell Disease Severity: Its Role in Steady-State and in Crisis Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 975-975 ◽  
Author(s):  
Magda Oliveira Seixas Carvalho ◽  
Larissa Carneiro Rocha ◽  
João Henrique Oliveira Reis ◽  
Théo de Araújo Santos ◽  
Valma Maria Lopes do Nascimento ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Clinical Manifestations ◽  
Healthy Individuals ◽  
Cell Disease ◽  
High Concentration ◽  
Significant Difference ◽  
Free Heme

Abstract 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.

scholarly journals The Fc Receptor Polymorphisms and Expression of Neutrophil Activation Markers in Patients with Sickle Cell Disease from Western India

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Harshada K. Kangne ◽  
Farah F. Jijina ◽  
Yazdi M. Italia ◽  
Dipti L. Jain ◽  
Anita H. Nadkarni ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Manifestations ◽  
Western India ◽  
Genotypic Frequency ◽  
Cell Disease ◽  
Activation Markers ◽  
Initiation And Propagation ◽  
Significant Difference ◽  
The Common

Objective. Sickle cell disease has variable clinical manifestations. Activation of neutrophils plays an important role in the initiation and propagation of vaso occlusive crises which can be analysed by determining the expression of neutrophil antigens such as CD16, CD32, and CD62L. The common FcγR polymorphisms (FcγRIIA and FcγRIIIB) are considered to influence clinical presentation. This study focuses on distribution of FcγR polymorphisms and their association with neutrophil activity among the patients from western India.Methods. In this paper 127 sickle cell anemia patients and 58 patients with sickle-β-thalassemia (median age12±8.58 years) with variable clinical phenotypes along with 175 normals were investigated. FcγRs polymorphisms were analysed by RFLP and AS-PCR. Activation of neutrophils was measured by flow cytometry.Results. The genotypic frequency of the H/R genotype of FcγRIIA and the NA1/NA1 genotype of FcγRIIIB was significantly decreased in patients compared to normals (P-0.0074,P-0.0471, resp.). We found a significant difference in the expression of CD32 and CD62L among the patients as against normals. A significantly higher expression of CD32 was seen in the milder patients with the H/H genotype (P-0.0231), whereas the expression of CD16 was higher in severe patients with the NA2/NA2 genotype (P-0.0312).Conclusion. The two FcγR polymorphisms had significant association with variable phenotypes of sickle cell disease. The expression of CD62L decreased in our patients indicating activation of neutrophils.

scholarly journals Sickle Cell Education for Medical Professionals: A Pre and Post Test Analysis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5812-5812
Author(s):  
Diana D Simmons ◽  
Robert Lucia ◽  
Kay Linn Saving ◽  
Nicole Alwan
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Test Scores ◽  
Conflicts Of Interest ◽  
Learning System ◽  
Medical Professionals ◽  
Cell Disease ◽  
Learning Module ◽  
Significant Difference ◽  
Post Test

Abstract Background and Objectives: Sickle cell disease is a severe inherited form of anemia caused by a genetic mutation. Polymerization of hemoglobin leads to a cascade of effects decreasing blood flow. This causes tissue hypoxia leading to acute and chronic damage to the organs and endothelial lining. This disease requires complex management that relies on comprehensive training and knowledge regarding the disease process. Often accurate knowledge of sickle cell disease and how to provide appropriate care in the general medical population is limited. The purpose of this project was to develop a sickle cell educational training module for medical professionals. Such a module could be used to guide the provision of accurate education regarding sickle cell disease and best practice when caring for this patient population. Methods: Goals and learning objectives were created and current medical literature about caring for sickle cell disease was reviewed. A comprehensive PowerPoint presentation was produced along with a provider tip sheet and a pre and posttest. The presentation, tip sheet, and tests were reviewed by a board certified pediatric hematologist/oncologist along with the hospital's educational review committee in the Department of Professional Regulation. Once approved, the PowerPoint, tip sheet, and tests were combined into a learning module and uploaded onto an online learning system utilized by the hospital system. The module was sent to over 2,400 outpatient providers and staff and to all inpatient staff on units where sickle cell patients stay when admitted. The module consisted of the participant completing a 10 question pretest, then reviewing the PowerPoint presentation and tip sheet. Following the review of the PowerPoint and tip sheet, the participant completed a 10 question posttest and completed an evaluation of the module. Analysis: There were 223 people who completed the Sickle Cell Disease Learning Module. A paired t-test was conducted to compare pre-test scores to post-test scores. There was a significant difference in the pre-test scores (M = 5.98, SD = 1.66) and post-test scores (M = 9.17, SD = 1.36); p = <0.0001. Conclusion: The goal of this module was to increase baseline medical knowledge of sickle cell disease. The results indicate there was statistically significant improvement in baseline knowledge, based on pre and post data (p = <0.0001). While the results indicate statistically significant increases in performance, it would be important to see if improvements are sustained over time. Reassessment of participants one year after completion of module can be beneficial to see if learned knowledge has been retained. Disclosures No relevant conflicts of interest to declare.

An Elevated TRV Is Associated with Venous Thromboembolism in Sickle Cell Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3222-3222
Author(s):  
Rachel M Adams ◽  
Lianne S Kopel ◽  
Demedrick Anton Bland ◽  
Elizabeth S Klings
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Medical Center ◽  
Heart Catheterization ◽  
Cell Disease ◽  
Complete Evaluation ◽  
Ct Angiogram ◽  
Significant Difference ◽  
History Of

Abstract Abstract 3222 Objective: An elevated tricuspid regurgitant jet velocity (TRV) by echocardiography, used to screen for pulmonary hypertension (PH) and mortality in sickle cell disease (SCD), likely has a multi-factorial etiology. SCD is a hyper-coagulable state, yet, the contribution of venous thromboembolic disease (VTE) to an elevated TRV is unknown. Based on the known association between VTE and PH, we hypothesized that SCD patients with an elevated TRV will have an increased prevalence of VTE. Methods: We reviewed data collected prospectively as part of the PH in SCD study conducted at Boston University/Boston Medical Center from 2004–2010. Subjects were included if they underwent both echocardiography and testing for VTE. An elevated TRV was defined as > 2.5 m/sec or the presence of PH on right heart catheterization. A history of VTE was defined by a positive CT/angiogram, ventilation/perfusion scan or Duplex ultrasound of an extremity (not catheter-related). Data were analyzed using a Chi-Square test and an odds ratio for VTE was calculated. Results: We reviewed the records of 162 patients enrolled in the PH of SCD study; 97 underwent both echocardiography and an evaluation for VTE.5/53 patients (9.4%) with normal echocardiography had a history of VTE, compared with 13/44 (29.5%) in the elevated TRV group. SCD patients with an elevated TRV were four times more likely to have a history of VTE compared to those with a normal echocardiogram (OR: 4.03, 95% CI 1.31–12.41, p=0.011). There was no significant difference in age, gender, history of asthma, hemoglobin genotype, hematologic profiles or renal function between patient groups. Conclusion: An elevated TRV and PH are associated with a history of VTE in SCD patients. This suggests a role for thrombosis in disease modulation and underscores the need for a complete evaluation for VTE in SCD patients with an elevated TRV. Disclosures: No relevant conflicts of interest to declare.

A Multicentre Study of Environmental Factors on the Severity of Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4841-4841
Author(s):  
Sanjay Tewari ◽  
Fred Piel ◽  
Valentine Brousse ◽  
Baba PD Inusa ◽  
Paul Telfer ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Environmental Factors ◽  
Sickle Cell ◽  
Hospital Admissions ◽  
Conflicts Of Interest ◽  
Acute Chest Syndrome ◽  
Electronic Patient Records ◽  
Cell Disease ◽  
Hospital Data ◽  
Significant Difference

Abstract Background: Sickle cell disease (SCD) is a very variable condition, with some patients being asymptomatic and others admitted frequently to hospital. Genetic factors have been extensively investigated but only explain a small amount of the variability to date. Environmental factors are undoubtedly important, but have not been studied in depth, at least in part because of the difficulty of conducting these studies. We have analysed the role of climatic, environmental and temporal factors in determining the frequency of hospital admissions in children with SCD to 4 large sickle cell centres in London and Paris. Participants and Methods: Clinical data were collected from 1st January 2007 to 31st December 2012. Inclusion criteria were children with SCD (HbSS and HbSC) between the ages of 0 and 17 years, admitted to hospital with acute pain, acute chest syndrome or fever. All children lived within 4 miles radius (London) or 10km (Paris) of the hospital. Data were collected using specific electronic patient records of SCD patients. Data were collected on the reason for admission, date and length of admission. Daily air quality records were collected from sites around Paris and London, including details of black smoke, particulate matter, nitric oxide, carbon monoxide, sulphur dioxide and ozone. Daily meteorological records were obtained from weather stations in London and Paris including wind speed, temperature, rainfall and humidity. Statistical analysis including time series studies were conducted using R software version 3.1.1. Results: There were a total of 2717 admissions over the six year study period. Overall for the London hospitals there was a mean of 0.39 admissions/patient/year, with 1406 admissions for pain, 153 for acute chest syndrome and 417 for fever. The rate of admission/patient/year by cause for HbSS and HbSC across the London hospitals is shown in table below: Table 1. Rates of admission/patient/year by cause Sickle genotype/cause of admission All London hospitals Institution A Institution B Institution C HbSS (Pain) 0.31 0.18 0.40 0.43 HbSS (Fever) 0.09 0.03 0.15 0.11 HbSS (acute chest syndrome) 0.04 0.03 0.04 0.04 HbSC (pain) 0.07 0.03 0.08 0.10 HbSC (fever) 0.03 0.01 0.04 0.05 HbSC (acute chest syndrome) 0.004 0.008 0.002 0.002 Overall admission numbers were significantly higher on Mondays and Tuesdays in London but there was no such variation in Paris (Table 2). Table 2. Mean number of admissions on days of week in Paris (1 hospital) and London (3 hospitals). ** denotes significant difference from mean of other days (P<0.001). London Paris Weekday Monday 0.75** 0.35 Tuesday 0.77** 0.36 Wednesday 0.66 0.36 Thursday 0.64 0.32 Friday 0.60 0.32 Saturday 0.51 0.20 Sunday 0.57 0.27 There was no seasonal variation in admission numbers in London, but significantly higher numbers of patients admitted in Paris during autumn and winter. Table 3. Mean number of seasonal admissions in Paris (1 hospital) and London (3 hospitals). ** denotes significant difference from mean of other days (P<0.001). London Paris Season Autumn 0.70 0.35** Spring 0.60 0.31 Summer 0.64 0.25 Winter 0.62 0.34** Conclusion In London, there is a 2-3 fold variation in admission rates for the same complications between different hospitals. Similarly there is a significant difference on the effects of season and weekday between Paris and London. These results are statistically stronger than many effects which are identified in genetic and therapeutic studies, and show the importance of environmental and cultural factors, which are potentially modifiable. The effect of weather and pollution on hospital admissions is currently being analysed. Disclosures No relevant conflicts of interest to declare.

scholarly journals Evidence for Transient Acute Liver Injury in Mouse Models of Sickle Cell Disease during Steady State Health

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1373-1373 ◽  
Author(s):  
Nancy J. Wandersee ◽  
Sandra L. Holzhauer ◽  
Dawn M. Retherford ◽  
Thomas D. Foster ◽  
Cheryl A. Hillery
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Liver Injury ◽  
Mouse Models ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Organ Injury ◽  
State Health ◽  
Cell Disease ◽  
Over Time

Abstract Individuals with sickle cell disease experience episodes of acute vaso-occlusive complications interspersed by periods of feeling well and apparent health during “steady state”. It is likely that episodic and subclinical sickling and vaso-occlusion occur on an ongoing basis even during periods of steady state. In order to determine whether mice with sickle disease have acute vaso-occlusion sufficient for organ injury at apparent steady state health, we chose to study 2 mouse models of severe sickle cell disease with serial blood draws over time. Since we have shown in previous studies that the liver is highly susceptible to acute sickling/vaso-occlusion induced by hypoxia, we first examined serial ALT measurements in a total of 13 Berkeley sickle cell (BERK-SS) mice, initially from week-to-week and month-to-month, and then day-to-day time frames. Individual BERK-SS mice showed week-to-week and month-to-month variations of up to 5-fold over baseline ALT levels, followed by return to baseline levels in most mice. This suggests that BERK-SS mice, during steady state health, experience acute, yet transient, liver injury. Surprisingly, we also found day-to-day variations of up to 3-fold in ALT levels in BERK-SS mice. To determine if these changes in ALT levels were mirrored by changes in other biomarkers, we measured serum amyloid P (SAP) as a marker of acute inflammation (similar to CRP in humans) in the same plasma samples. We found up to 1.6-fold variation in SAP over baseline plasma levels over time. However, there was less overall variation in SAP levels in individual mice compared to the striking changes in ALT. In addition, we found that variations in SAP did not consistently precede, follow, or coincide with variations in ALT levels, suggesting that SAP is a marker of sickle cell-induced inflammation or vaso-occlusion independent of liver injury. We next sought to confirm our findings with daily serial ALT and SAP measurements from Townes sickle cell (TOWNES-SS) mice (n=8), a second commonly used mouse model of severe sickle cell disease. Our data showed that baseline ALT levels are higher and SAP levels are lower in TOWNES-SS as compared to BERK-SS mice, likely reflecting differences in strain background between the two models. However, we again found daily fluctuations in ALT and SAP levels in individual TOWNES-SS mice, similar to those seen in individual BERK-SS mice. We propose that these temporal variations indicate that both the Berkeley and Townes mouse models of sickle cell disease exhibit fluctuations in steady state health, similar to those seen in human individuals with sickle cell disease. In addition, the results suggest that studies in these mouse models should be designed and interpreted with these temporal fluctuations in mind. Disclosures No relevant conflicts of interest to declare.

scholarly journals Steady State Predictors of Mortality in Adults with Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1388-1388
Author(s):  
Susanna A Curtis ◽  
Neeraja Danda ◽  
Zipora Etzion ◽  
Hillel W Cohen ◽  
Henny H Billett
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Reticulocyte Count ◽  
Conflicts Of Interest ◽  
Treatment Modalities ◽  
Mortality Data ◽  
Cell Disease ◽  
Ed Visits ◽  
Over Time

Abstract Background: With improved treatment modalities, longevity for sickle cell disease (SCD) is increasing. Yet there is still a subgroup of adult patients whose survival rate has not improved. These patients, if well defined by evidence based decisions, might be those for whom more aggressive disease modifying therapy would be appropriate. Methods: We identified all patients with SS/Sβ0 seen at our medical center in 2002 whom we were still following in 2012 as well as those who had died between 2002 and 2012. Patients with SC and Sβ+ thalassemia were excluded. ED, clinic, and inpatient admissions over the entire years 2002 and 2012 were obtained. All 2002 and 2012 steady state parameters for a given laboratory test for a given patient were averaged. “Steady State” was defined as those values not within one day of an ED visit or within one week of a hospital admission. Data were assessed for normality; parametric and non-parametric bivariate tests were performed as appropriate. Data from 2002 and 2012 was compared with paired-T tests. Mortality data were analyzed using Kaplan-Meier curves and Cox proportional hazard models. Results: We identified 289 SS/Sβ0 patients in 2012 (ages 18-87, 54% female) who had been present in our system in 2002 (survival cohort). We also identified 70 patients present in 2002 (ages 19-88 at death, 47% female) who had died between 2002 and 2012, inclusive (mortality cohort). Average age at death was 42.1±14.0 years, median survival was 58.3 years (95% CI: 54.5 – 63.0). Survivors had, in 2002, higher HbF, Hb, higher MCHC, lower white blood cell (WBC) counts and creatinine (Cr) levels, and fewer admissions than those who did not survive past 2012 (Table 1). Absolute Reticulocyte count (Retic), MCV, LDH, liver function tests, ED and clinic use were not significantly different between survivor and mortality groups. Cox proportional hazards model showed increased hazard ratios with lower HbF, higher WBC, Cr and increased admissions. When the survivors from 2002 were compared to themselves in 2012, they were shown to decrease HbF, Hb, MCHC, WBC, alkphos, and total bilirubin over time and to increase admissions, ED visits, Retic, MCV, Cr, and weight. Clinic visits, direct bilirubin and LDH were not significantly different. Conclusions: As therapeutic alternatives increase, it may be important to tailor therapy, and the need for better prognostic markers becomes ever more important. We observed here that several known mortality predictors evolve over time. As the “survivor” population ages, they may begin to resemble those with a poorer prognosis with decreased Hb and HbF levels but increased admissions and ED visits. However in our sample, WBC, a recognized factor in mortality and morbidity, decreased further over time in those who survived. Similarly, absolute reticulocyte count increased further over time in the survivors, suggesting an ability of the marrow to respond to the increased anemia. Further studies should be done to distinguish which biomarkers, at what level and in what age groups, are truly predictive of severity in sickle cell disease. Abstract 1388. Table 1: Comparison of 2002 SCD cohort who survived until 2012 with those who did not (left panel) and of a subset of this survivor population with themselves in 2012 2002 All Patient Data Matched Data 2002&2012 Survivor 2002 Mortality 2002 Cox Hazard Survivor 2002 Survivor 2012 N 289 70 359 134 134 Hb (g/dL) 8.5±1.4 7.8±1.4* .82(.65-1.02) 1g/dL 8.4±1.4 8.1±1.5* MCHC (g/dL) 35.2±1.2 34.5±1.8* .85(.69-1.04)1g/dL 35.1±1.2 34.2±1.3# Retic (x10^9/L) 181.3(131.9/237.8) 183.4(128.5/218.2) 1.00(1.00-1.01) 1k/uL 185.9(144.0/236.8) 247.4(168.1/341.2)# WBC (x10^9/L) 11.6±3.6 12.4±4.5 1.11(1.02-1.21)* 1 k/Ul 11.6±3.5 10.8±4.1* Cr (mg/dL) 0.5(0.6/0.7) 0.8(0.6/1.5)# 1.25(1.00-1.55)* 1mg/dL 0.6(0.5/0.7) 0.7(0.6/0.9)# Alb (g/dL) 4.3±.3 4.1±.4# .72(.33-1.57) 1g/dL 4.3±.3 4.2±.5 AlkPhos (U/L) 103.0(86.8/159.8) 121.0(99.6/166.8) 1.3(.91-1.99) 100 U/KL 111.0(86.8/165.0) 91.3(70.0/125.1)# Weight (KG) 58.3±21.3 64.1±15.7* 1.00(.98-1.02) 1 KG 58.4±21.1 66.0±13.9# HbF (%) 15.7(8.4/20.1) 5.5(1.9/12.4)# .94(.90-.98)# 1% 15.9(7.4/20.5) 6.4(4.1/11.8)# ED (per year) 2.6±3.9 1.9±3.3 .96(.88-1.04) 1/year 2.6±3.9 5.2±10.7# Clinic (per year) 6.8±8.3 8.3±11.5 1.01(.99-1.04) 1/year 6.8±8.3 7.3±10.5 Admits (per year) 0.3±0.8 2±2.5# 1.28(1.18-1.38)# 1/year 0.3±0.8 2.1±3.2# *=p<.05, #=p<.01 Disclosures No relevant conflicts of interest to declare.

scholarly journals Vitamin D level, lipid profile, and vitamin D receptor and transporter gene variants in sickle cell disease patients from Kurdistan of Iraq

2021 ◽  
Author(s):  
Abdalla Hussein Hama ◽  
Ebrahim Shakiba ◽  
Zohreh Rahimi ◽  
Mehran Karimi ◽  
Hadi Mozafari ◽  
...  
Keyword(s):  
Vitamin D ◽  
Sickle Cell Disease ◽  
Lipid Profile ◽  
Total Cholesterol ◽  
Vitamin D Deficiency ◽  
Sickle Cell ◽  
Healthy Individuals ◽  
Cell Disease ◽  
Mineral Density ◽  
Significant Difference

Abstract Background. Sickle cell disease patients are susceptible to the development of vitamin D deficiency. Vitamin D through binding to vitamin receptor (VDR) exerts its function and affects gene transcription in target tissues. Also, VDR variants could affect bone mineral density. Methods. In a case-control study 101 sickle cell disease patients including 61 SS, 39 S/β-thalassemia, and 1 SD along with 110 healthy individuals from Kurdistan of Iraq were studied. The lipid profile, vitamin D level, FokI, and TaqI variants of VDR and group-specific component (GC) were detected using the standard enzymatic method, the immunodiagnostic systems limited EIA kit and PCR-RFLP methods, respectively. Results. Around 93 and 82% SS and S/β thalassemia patients, respectively had vitamin D deficiency compared to 83% healthy individuals. Severe vitamin D deficiency (<10 ng/ml) was detected in 78.7% of SS patients. Plasma levels of total cholesterol, HDL-C, and LDL-C in SCD patients were significantly lower compared to controls. Vitamin D levels were negatively correlated to TG and positively correlated to total cholesterol and HDL-C. The frequencies of the C allele of FokI were 81.7 (p=0.003), 80.2 (p=0.034), and 84.6% (p=0.011) in all SCD, SS, and SS/βthal patients, respectively compared to 69.1% in controls. However, no significant difference was detected by comparing the frequencies of VDR TaqI and GC polymorphisms between SCD patients and controls.Conclusion. In the present study we found hypocholesterolemia, high prevalence of VDR FokI C allele, and low vitamin D level among children and adults with SCD patients from Kurdistan of Iraq.

Report on the International Co-Operative Study of the Effects of L-Selectin Gene Polymorphisms on the Development of Complications in Sickle Cell Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3775-3775
Author(s):  
Iheanyi Okpala ◽  
Cynthia C. Ugochukwu ◽  
Panagiotis Pantelidis ◽  
Baba Inusa ◽  
Obike Ibegbulam ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Surface Expression ◽  
Control Individual ◽  
Acute Chest Syndrome ◽  
Nucleotide Polymorphisms ◽  
Cell Disease ◽  
Increased Risk ◽  
Significant Difference

Abstract Our previous study showed that patients with sickle cell disease (SCD) and high steady-state expression of the adhesion molecules L-selectin and αMβ2 integrin on leukocytes developed complications [Blood. 2002;100(suppl):11a. Eur J. Haematol. 2002; 69:135–144]. The aim of this study was to find out if L-selectin protein expression by leukocytes and the development of complications in SCD are affected by previously described single nucleotide polymorphisms within the coding regions of the gene. To detect F206L, T49S and P213S polymorphisms we determined the L-selectin genotype in 142 HbSS patients (64M, 78F, age 2 – 62 yr, mean 27 yr ±12); and 102 racially-matched HbAA controls with similar age and sex distribution. The T49S and P213S amino acid changes in L-selectin are respectively associated with increased risk of vasculopathy and nephropathy; important features of SCD. [Hum Genet. 1996; 97:15–20. Am. J. Hum. Genet.2002; 70: 781–786]. All HbSS patients were evaluated for disease complications. Steady-state expression of L-selectin on neutrophils, lymphocytes and monocytes was measured by flow cytometry in 44 HbSS patients. With respect to F206L polymorphism, 100/142 (70%) patients and 73/102 (72%) controls were FF homozygous, 42 patients and 28 controls were heterozygous FL, and 1 control individual was LL homozygous. There was no significant difference in distribution of the polymorphic variants between patients and controls [Chi-squared (X2) = 0.1, p&gt;0.05]. In codon 213, 48 (33.8%) patients and 42 (41.2%) controls were PP homozygous, 91 patients and 55 controls PS heterozygous, 1 patient and 5 controls SS homozygous [X2 =1.9, p&gt;0.05]. With regard to the T49S polymorphism, 100% of the patients and controls were TT homozygous. At least one complication of SCD was observed in 110 SCD patients; 32 had uncomplicated disease. The most common complications observed were avascular joint necrosis (n=39), sickle nephropathy (n=31), stroke (n=25) and acute chest syndrome (n=20). The observed frequencies of FF genotype in codon 206 among patients with complications (74), and without complication (26) were not significantly different from the expected values [X2 = 2.37, p&gt;0.05]. Similarly, none of the other genotypes (FL, PP, PS) was significantly associated with complications of SCD. Of the 44 patients in who leukocyte L-selectin expression was measured, 31 turned out to be FF homozygous in codon 206, and 13 FL. No significant differences were observed between FF and FL patients in the mean levels of L-selectin expression by neutrophils (FF: 4.00+ 4.56 vs FL: 3.24+ 3.4), monocytes (FF: 4.30+ 5.6 vs FL: 2.56+ 3.39) or lymphocytes (FF: 2.61+ 3.02 vs FL: 2.11+ 2.0); p&gt;0.05. Similarly, the P213S polymorphism had no effect on the level of L-selectin expression. The findings suggest that neither F206L nor P213S L-selectin gene polymorphism predisposes to high leukocyte surface expression of this adhesion molecule, or the development of complications in SCD.

Etiology of and Associations with Early Death in Adult Patients with Sickle Cell Disease At a Single Referral Institution.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2117-2117
Author(s):  
Courtney Fitzhugh ◽  
Darlene Allen ◽  
Wynona Coles ◽  
Cassie Seamon ◽  
Xiongce Zhao ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Cause Of Death ◽  
Sickle Cell ◽  
Causes Of Death ◽  
Conflicts Of Interest ◽  
Organ Damage ◽  
Death Certificates ◽  
Cell Disease ◽  
Organ Function ◽  
Significant Difference

Abstract Abstract 2117 Sickle cell disease (SCD) causes significant morbidity and early mortality. The largest study to date reported in 1994 a median survival of 42 years for men and 48 years for women with homozygous SCD1. One third died during a vaso-occlusive crisis, and 18% died of acute organ failure. Circumstances of death were unknown in 18% of patients. With improved patient care in the current era including hydroxyurea (HU) therapy, we sought to identify age and causes of death and associated clinical variables in adults with SCD at a single referral institution. We first reviewed death certificates and assigned one or more causes of death based on all listed data. We studied autopsy reports and medical records and communicated with medical providers when available to identify further causes of death. We then performed a cross sectional analysis of clinical features obtained at initial enrollment and compared those variables in patients who are now living versus deceased using univariate t-test or Chi-squared analysis in order to determine which factors may be associated with death. 528 patients with SCD evaluated at the National Institutes of Health between 2001 and 2010 were included. Out of 511 patients with known genotypes, 391 patients had homozygous SCD. 85 of 528 (16%) died at a median age of 43 years for men and 44 years for women. Death certificates were available for 55 (65%) patients. SCD and infection were the most common listed cause of death (12% each), followed by pulmonary hypertension and/or cor pulmonale (9%), cardiac etiology (8%), narcotic toxicity (7%), and other (31%). Cause of death was unavailable in 18 (21%) cases. Deceased patients were significantly older at the time of first enrollment compared to living patients (41.5 vs. 34.1 years, p<0.0001). There was no significant gender difference between groups. There was also no significant difference in the reported use of HU or fetal hemoglobin levels. Enrollment laboratories suggesting renal insufficiency in deceased patients included a higher creatinine, phosphorus, and uric acid (p<0.02). Hepatic dysfunction was also more prevalent in the deceased group as evidenced by significantly higher direct bilirubin and alkaline phosphatase and lower albumin (p<0.005). There was no difference in alanine transaminase levels. Lactate dehydrogenase (LDH) was significantly higher in deceased patients (p=0.01). As there was no significant difference in hemoglobin, indirect bilirubin, or absolute reticulocyte counts between groups, higher LDH in deceased patients suggests a non-erythrocytic source. Ferritin levels and percent saturation of transferrin were significantly higher and transferrin significantly lower (p<0.004) suggesting more iron overload in deceased patients. Lastly, brain natriuretic peptide levels (reported only in patients with creatinine <1mg/dL) and tricuspid regurgitant velocity were also significantly increased (p<0.0001), suggesting higher prevalence of cardiopulmonary disease in deceased patients. In summary, the most common listed cause of death was nonspecific and unrevealing, reported as SCD. Surprisingly, another common cause of death was infection. This may be due to the combination of poor organ function reserve and functional asplenia. Deceased subjects were older and more likely to have organ impairment at initial evaluation. These data suggest that while contemporary management of patients with SCD may decrease acute manifestations, end organ damage still occurs. Lastly, markers of organ function should be closely monitored as patients increase in age, and organ-specific and definitive disease-specific therapy should be considered before irreversible organ damage ensues. 1 Platt OS et al. NEJM, 1994. 330(23): 1639–1644. Disclosures: No relevant conflicts of interest to declare.

The Effect Of Microalbuminuria On Duration Of Hospitalization In Adult Sickle Cell Disease Patients With Pain Crisis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4694-4694
Author(s):  
Mohammed Shaik ◽  
Borys Hrinczenko
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Categorical Variables ◽  
Cell Disease ◽  
Exact Test ◽  
Blood Disorder ◽  
Significant Difference ◽  
Pain Crisis

Introduction Sickle cell disease (SCD) is a genetic blood disorder of hemoglobin resulting in severe morbidity and early mortality. The prevalence of microalbuminuria and/or proteinuria in children with SCD varies from 18 to 28% and increases with age. However, the exact prevalence in adults in not known. In the general population, the presence of albuminuria has been shown to be associated with all cause mortality. The urine microalbumin to creatinine ratio (MA) is considered to be an early sign of impending sickle cell nephropathy. We sought to investigate the association of MA with various SCD genotypes (HbSS, HbSC, HbS/β-thalassemia) in our clinic and also the length of stay (LOS) in hospitalized SCD patients with acute pain crisis. Methods Twenty-eight consecutive SCD patients diagnosed in our clinic by hemoglobin electrophoresis were included in our study. The patients (pts) age, gender, hemoglobin electrophoresis, and baseline MA were obtained. Based on their MA level they were divided into two groups, abnormal MA (MA ≥ 30 mg/g creatinine) or normal MA (< 30 mg/g creatinine). Eleven of these 28 patients were eventually hospitalized for a sickle cell related pain crisis. Their MA level was obtained within 24-hours of hospital admission and their hospitalization length of stay (LOS) was also recorded. We analyzed the association between the two groups of patients, those with normal or abnormal MA, with the different genetic variants of SCD in both our clinic and hospitalized pts. Furthermore, for hospitalized pts we also assessed an association of MA with their mean LOS. The Chi-square test/Fisher’s exact test was used for categorical variables and the T-test/Mann-Whitney test was used for numerical variables. Results All twenty-eight patients were African American without significant renal impairment, with 11, 10, and 7 pts with SS, SC and S β-thalassemia (Sβ), respectively. Fifteen of these pts had abnormal MA, 12 pts were female. The median age was 35.5 yrs (range, 19 - 59), median LOS was 3.5 days (range, 2-8). The SS pts had higher abnormal MA levels followed by SC and then Sβ (p=0.03) (Table 1). There was no significant difference in gender between the two groups (p=0.2). SCD pts admitted to the hospital for pain crisis with an abnormal MA within 24-hours of admission had a significantly higher mean LOS when compared to pts with normal MA (p=0.0089) (Table 1). Conclusion Microalbuminuria is more prevalent in the severe genotypes of SCD disease such as SS and SC vs. Sβ pts. Thereby, MA might be a useful biomarker of generalized SCD vasculopathy, in addition to a known marker of progressive nephropathy. Furthermore, MA has a significant impact on length of hospitalization. An abnormal MA obtained within the first 24-hrs of hospitalization of a SCD pt in pain crisis was predictive of prolonged hospital duration. Early and more aggressive supportive care symptom management for those patients might be a reasonable option but requires more study. Further large prospective clinical trials are needed to validate our findings. Disclosures: No relevant conflicts of interest to declare.

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