Renal Disease in Sickle Cell: Clinically Varied and Associated with Increased Mortality

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 90-90
Author(s):  
Sabarish Ayyappan ◽  
Paul Drawz ◽  
Mehdi Nouraie ◽  
Mariana E Hildesheim ◽  
Yingze Zhang ◽  
...  
Keyword(s):  
Renal Function ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Multivariate Analyses ◽  
Conflicts Of Interest ◽  
Laboratory Data ◽  
Red Cell ◽  
Cell Disease ◽  
Cell Destruction ◽  
Increased Risk

Abstract Abstract 90 The Walk-Phasst Study of sickle cell disease (SCD) affords a unique opportunity to examine renal function in a large number of adults with SCD. Extensive clinical and laboratory data were obtained on 463 adults with HbSS and 127 adults with HbSC. Where possible, correlates for estimated glomerular filtration rate (eGFR, calculated by the 4-value MDRD equation) and albuminuria/proteinuria were also evaluated in historical data, from SS adults in the CSCCD cohort and the Multicenter Study of Hydroxyurea (MSH) in sickle cell disease. Adjusted decline in eGFR was more rapid in SS compared with SC, at −2.6 and −0.92 ml/min/1.73 m2/year, respectively (p<0.001). In SS, similar declines in cross-sectional eGFR with age were seen in adults in the CSCCD (n=705) and MSH (n=298) cohorts, at −2.9 and −1.9 ml/min/year (BSA corrected), respectively. Multivariate analysis of the SS cohort in of Walk-Phasst revealed that depressed eGFR values were associated with an elevated estimated pulmonary arterial systolic pressure (as reflected in a higher tricuspid regurgitant jet velocity, measured by echocardiogram, p=0.007) and with evidence for inflammation (an elevated white blood cell count, p=0.018). In SC adults, in contrast, lower eGFRs were primarily associated with a diminished erythroid reserve (depressed absolute reticulocyte counts, P=0.005). Albuminuria (≥30 mg albumin/gm creatinine) was detectable in 66 and 41 % of adults with HbSS and HbSC in Walk-Phasst (185/287 evaluable SS and 25/61 evaluable SC, p=0.001). In Walk-Phasst, albuminuria in SS was associated with evidence of increased red cell destruction (lower total hemoglobin (P=0.07), higher LDH (P<0.001), and higher reticulocyte count (P=0.017)). In SC, albuminuria was associated with a higher LDH (P=0.01). 159/657 (24%) of adult SS subjects in the CSCCD cohort had trace to 4+ proteinuria, using a method (urine dipstick analysis) that is less sensitive and less quantitative than the albumin-to-creatinine ratio used in Walk-Phasst. Multivariate analyses again suggested a strong association between a depressed Hgb and proteinuria (P<0.001) in CSCCD, and LDH was also associated with proteinuria, in univariate analyses (P<0.001). In Walk-Phasst the absence of albuminuria in all subjects with SCD was associated with lesser mortality in multivariate analyses (Hazard ratio 0.62 (0.4–0.9, P=0.02). No similar association was seen between eGFR and mortality. Subjects with SS in Walk-Phasst had depressed serum bicarbonate levels, of 23.8±3.4 compared with 24.7±3.2mEq/dL in SC (p<0.005) and 24.8±3.3 mEq/dL in the non-CKD general population (Shah et al, 2009). In multivariate analyses, acidemia was associated with both increased destruction and decreased production of red cells, e.g. higher EPO (P=0.003) and total bilirubin levels (P<0.001), but lower reticulocyte counts (P=0.06). Impaired physiologic functioning in acidemic subjects with HbSS, manifest as a depressed 6MWD (P<0.001) and a lower eGFR (P<0.001), was seen. No effect of bicarbonate level on mortality in SCD patients was evident in Walk-Phasst. In conclusion, renal function is perturbed in sickle cell syndromes in several ways, including more rapid decrement in eGFR, highly prevalent albuminuria, and, in SS, marked abnormalities in acid-base balance. Albuminuria is associated with anemia in two large cohorts of sickle cell disease patients and, in Walk-Phasst, with evidence for enhanced red cell destruction. Importantly, albuminuria correlated with an increased risk for mortality in sickle cell disease. (We acknowledge the many contributions made by the Walk-PHASST Investigators: Badesch DB, Barst RJ, Castro OL, Girgis RE, Gibbs JS, Goldsmith JC, Hannoush H, Hassell KL, Kato GJ, Krishnamurti L, Lanzkron S, Machado RF, Morris CR, Novelli EM, Rosenzweig EB, Sachdev V, Schraufnagel DE, Taylor JG 6th.) Disclosures: No relevant conflicts of interest to declare.

scholarly journals American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support

2020 ◽  
Vol 4 (2) ◽  
pp. 327-355 ◽  
Author(s):  
Stella T. Chou ◽  
Mouaz Alsawas ◽  
Ross M. Fasano ◽  
Joshua J. Field ◽  
Jeanne E. Hendrickson ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Guideline Development ◽  
Practice Research ◽  
Evidence Based ◽  
Red Cell ◽  
Cell Disease ◽  
American Society

Background: Red cell transfusions remain a mainstay of therapy for patients with sickle cell disease (SCD), but pose significant clinical challenges. Guidance for specific indications and administration of transfusion, as well as screening, prevention, and management of alloimmunization, delayed hemolytic transfusion reactions (DHTRs), and iron overload may improve outcomes. Objective: Our objective was to develop evidence-based guidelines to support patients, clinicians, and other healthcare professionals in their decisions about transfusion support for SCD and the management of transfusion-related complications. Methods: The American Society of Hematology formed a multidisciplinary panel that was balanced to minimize bias from conflicts of interest and that included a patient representative. The panel prioritized clinical questions and outcomes. The Mayo Clinic Evidence-Based Practice Research Program supported the guideline development process. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to form recommendations, which were subject to public comment. Results: The panel developed 10 recommendations focused on red cell antigen typing and matching, indications, and mode of administration (simple vs red cell exchange), as well as screening, prevention, and management of alloimmunization, DHTRs, and iron overload. Conclusions: The majority of panel recommendations were conditional due to the paucity of direct, high-certainty evidence for outcomes of interest. Research priorities were identified, including prospective studies to understand the role of serologic vs genotypic red cell matching, the mechanism of HTRs resulting from specific alloantigens to inform therapy, the role and timing of regular transfusions during pregnancy for women, and the optimal treatment of transfusional iron overload in SCD.

Polymorphisms in TNFα Are Associated with Cerebrovascular Events in Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1540-1540 ◽  
Author(s):  
Latorya A Barber ◽  
Allison E Ashley-Koch ◽  
Melanie E. Garrett ◽  
Karen L Soldano ◽  
Marilyn J. Telen
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Umbilical Vein ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Data Set ◽  
Clinical Complications ◽  
Cerebrovascular Events ◽  
Increased Risk

Abstract Abstract 1540 Poster Board I-563 Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine that stimulates phagocytosis, neutrophil recruitment, and expression of adhesion molecule VCAM-1. Plasma levels of TNFα have been found to be increased in sickle cell disease (SCD), and in vitro studies show that TNFα causes increased adherence of sickle red blood cells to human umbilical vein endothelial cells. A polymorphism in the promoter region of the TNFα gene has previously been associated with stroke in children with SCD (Hoppe et al., 2007). The current study was designed to identify associations of additional TNFα single nucleotide polymorphisms (SNPs) with SCD clinical complications. We analyzed five SNPs in the TNFα gene in 509 DNA samples of SCD patients from Duke University, University of North Carolina at Chapel Hill, and Emory University. In our data set, cerebrovascular events (CVEs), including overt stroke, seizures, and transient ischemic attacks, occurred in 133 out of 509 SCD patients (26.1%). SNP genotyping was performed using Taqman genotyping assays from Applied Biosystems. Due to low minor allele frequencies (<0.05) for all the SNPs examined, genetic associations with SCD clinical complications were examined by using allele tests. After controlling for age, gender, and use of hydroxyurea, two of the five TNFα SNPs, rs2228088 and rs3093665, were significantly associated with CVEs (p=0.013 and 0.029, respectively). The odds that SCD patients with a G allele at rs2228088 suffered from CVEs were 0.485 times that for patients with the T allele, suggesting that the G allele had a protective effect. The odds of having the A allele at rs3093665 and suffering from CVEs was also reduced, at 0.45 compared to the C allele. Neither SNP was found to be in linkage disequilibrium (LD) with any of the other SNPs analyzed (r2≤0.002). There was also strong association of SNP rs2228088 with acute chest syndrome (ACS; p=0.003), occurring in 382 out of 509 SCD patients (75%). However, in this analysis, the G allele was associated with increased risk for ACS (OR=2.313). In addition to the association with CVEs, the SNP rs3093665 was also significantly associated with priapism (p=0.03), reported by 86 of 223 male SCD patients (38.6%). In this analysis, the A allele was protective, as had been observed for CVE (OR=0.188). Additionally, we found no difference in steady state plasma TNFα levels between genotypes for the two SNPs. The functional significance of these SNPs is presently unknown. SNP rs2228088 is a synonymous SNP located in the coding region, and rs3093665 is located in the 3' untranslated region of the TNFα gene. While the G to T change at SNP rs2228088 does not translate to a change in amino acid sequence, the A to C change at SNP rs3093665 may affect mRNA stability due to its location. It is also possible that one or both of these SNPs is in LD with another functionally relevant SNP. Our findings thus support previous data implicating TNFα polymorphisms in risk for central nervous system events. Interestingly, ACS has been previously associated with seizures, stroke and altered mental status in adults and children with SCD (Vinchinsky et al., 2000) and with silent cerebral infarcts and reversible posterior leukoencephalopathy syndrome in children with SCD (Henderson et al., 2003). However, in our dataset, ACS and the occurrence of CVEs were not associated (p=0.24). Further studies are required to elucidate these and other factors that potentially correlate with SCD clinical complications. Disclosures No relevant conflicts of interest to declare.

Effect of Hydroxyurea on Elevated Pulmonary Artery Pressures in Children with Sickle Cell Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4841-4841
Author(s):  
Farzana Pashankar ◽  
Deepa Manwani ◽  
Margaret Lee ◽  
Nancy S. Green
Keyword(s):  
Sickle Cell Disease ◽  
Pulmonary Artery ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Laboratory Data ◽  
Fetal Hemoglobin ◽  
Total Daily Dose ◽  
Cell Disease ◽  
Biomarker Analysis ◽  
Significant Change

Abstract Abstract 4841 Background: Pulmonary hypertension (PHT) is a significant complication of sickle cell disease. Studies in children report a 16–30% prevalence of elevated pulmonary artery pressures, as estimated by measurement of tricuspid regurgitant jet velocity (TRV) on echocardiography. The pathogenesis of elevated pulmonary artery pressures is multifactorial, with hemolysis induced endothelial dysfunction playing a major role. More recent studies highlight the role of inflammation in the pathogenesis. Hydroxyurea is a well established treatment for sickle cell disease. It acts primarily by induction of fetal hemoglobin, thereby reducing hemolysis, with possible additional effects on vascular and endothelial function. The aim of this study was to determine if early detection and treatment with hydroxyurea will decrease elevated pulmonary artery pressures in children with sickle cell disease. Methods: The study was conducted at 3 centers. Children with Hb SS and Hb Sb0 thalassemia between the ages of 5–21 years, with a screening echocardiogram showing a TRV ≥ 2.5 m/sec were identified. An echocardiogram was repeated to confirm elevated TRV. Subjects with persistent elevation of TRV ≥ 2.5 m/sec on repeat echocardiogram, were consented and started on hydroxyurea at 20 mg/kg/d with escalation to a maximum tolerated dose or a total daily dose of 30 mg/kg/d. Laboratory data and echocardiograms were repeated at 6 and 12 months to measure effect of hydroxyurea on TRV. Additionally blood and urine samples were also collected pre treatment, at 6 and 12 months post treatment for biomarker analysis, which will be performed later. Baseline and 6 month laboratory and echocardiogram data were compared using paired t test. Results: Twelve patients were enrolled. Mean age was 12.25 years (range 6–19 years) with a M:F ratio of 2:1. Average follow up is 11 months. Patients tolerated hydroxyurea well, and in 90% of patients the dose was escalated to 30 mg/kg/d. 1 patient achieved MTD at 20 mg/kg/d. Two patients went off study at 4 and 5 months respectively. As shown in Table 1, six months after starting hydroxyurea there was a significant increase in mean oxygen saturation, hemoglobin, mean corpuscular volume and fetal hemoglobin. There was a significant decrease in mean reticulocyte count, LDH and white blood cell count. There was no significant change in TRV six months after treatment with hydroxyurea. Conclusion: Hydroxyurea significantly decreased measures of hemolysis in children with sickle cell disease. Six months after treatment with hydroxyurea, there was no significant change in estimated pulmonary artery pressures measured on echocardiography. The study is ongoing to see if hydroxyurea affects pulmonary artery pressures with a longer duration of treatment. Disclosures: No relevant conflicts of interest to declare.

Alloantibody Formation In Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2395-2395 ◽  
Author(s):  
Joep Sins ◽  
Saurabh Zalpuri ◽  
Marjon Cnossen ◽  
Anita W. Rijneveld ◽  
Jean-Louis Kerkhoffs ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
General Population ◽  
Sickle Cell ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Cumulative Number ◽  
Cell Disease ◽  
Cox Regression Analysis ◽  
Increased Risk

Abstract Background Transfusion of red blood cells (RBC) is a common intervention to treat and prevent complications in sickle cell disease (SCD). However, frequent transfusions may lead to erythrocyte alloimmunization, thereby complicating donor matching procedures and posing patients at risk for hemolytic transfusion reactions. Little information is available about the risk of alloimmunization of sickle cell patients living in European countries. In the Netherlands extensive matching procedures to prevent alloimmunization were introduced a decade ago, but the effect on alloimmunization has not been evaluated yet. Aims The primary aim of this study is to evaluate the cumulative incidence of first alloantibody formation in a Dutch cohort of transfused SCD patients, and to compare this with a general Dutch RBC-transfused population. In addition, the effect of extended RBC matching protocols on the incidence of alloantibody formation in SCD and potential clinical determinants of alloimmunization will be assessed. Methods We conducted a retrospective cohort study and collected data on SCD patients (genotypes HbSS, HbSC, HbSβ0 and HbSβ+ thalassemia), diagnosed in three Dutch Sickle Cell Treatment Centers that received non-extended matched (ABO, RhD) RBC transfusions between 1984-2004 and extended matched (at least ABO, Rhesus phenotype, Kell) RBC transfusions between 2004-2011. In addition, we compared this population with a general population of 3 042 patients that received non-extended matched (ABO, RhD) RBC transfusions between 2005-2009 in the Leiden University Medical Center (Zalpuri et al. 2012). Cohorts were not matched for ethnicity. Alloimmunization risk was calculated as Kaplan-Meier incidence with cumulative number of transfusions as time variable. The association with the clinical determinants gender, SCD-phenotype and ethnicity was analyzed with Cox-regression analysis. Results A total of 291 SCD patients received 7 957 RBC units. Alloantibody formation occurred in 52 (17.9%) patients. The cumulative incidence of alloimmunization was 9% after 5 RBC units, 15% after 10, 24% after 20 and 34% after 40 RBC units. Multivariate analysis, correcting for the cumulative number of transfusions, demonstrated a significantly increased risk of alloantibody formation in our SCD cohort when compared to a general population of transfused patients (HR 7.5 (95% CI: 5.06-11.14), where the cumulative incidence of alloimmunization was 1.1% after 5, 2.4% after 10, 3.4% after 20 and 6.5% after 40 RBC units. No association could be demonstrated between alloantibody formation and clinical determinants such as gender, SCD-phenotype or ethnicity. However, a significant reduction in alloimmunization was observed in SCD patients that received their first transfusion from the year 2004 onwards, after preventive matching for Rhesus phenotype and Kell was introduced for SCD patients (HR 0.48 (95% CI: 0.24-0.97)). Conclusion The overall rate of first RBC alloantibody formation in our cohort was 17.9% and the risk of alloimmunization increased substantially with an increasing number of RBC transfusions. A unique comparison with a general cohort of Dutch transfused patients demonstrates a significantly higher risk of alloantibody formation in SCD, acknowledging earlier findings. This may partially be explained by differences in RBC antigens between patients of African descent and the predominantly Caucasian donors. Besides the number of RBC units, no other clinical risk factors for allo-immunization in SCD could be identified. The effectiveness of extended RBC matching protocols in the prevention of alloimmunization for chronically transfused patients in the participating centers was confirmed. Disclosures: No relevant conflicts of interest to declare.

The Cerebral Vasculopathy In Malian Sickle Cell Anemia Children: Lesson From Routine Transcranial Doppler Screening

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4687-4687
Author(s):  
Dapa Aly Diallo ◽  
Aldiouma Guindo ◽  
Alain Dorie ◽  
Boubacari Ali Touré ◽  
Baba Fané ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Transcranial Doppler ◽  
Conflicts Of Interest ◽  
Fetal Hemoglobin ◽  
Preventive Treatment ◽  
Cell Disease ◽  
Control Center ◽  
Increased Risk ◽  
Patients At Risk

Cerebral vasculopathy is one of the major complications of Sickle Cell Disease (SCD). 11% of the homozygous SCD patients experience stroke by age of 20 years. The use of Transcranial Doppler (TCD) allows identification of patients at risk for stroke and leads to implementation of a preventive treatment that contributes to limit the burden of SCD particularly during childhood. Using TCD screening, we evaluated the prevalence and incidence of cerebral vasculopathy in Malian SCD children. During the years 2008 to 2013, 572 children, 249 girls and 323 boys, age range (2-17yrs) were routinely screened by TCD at our Sickle Cell Disease Research and Control Center of Bamako, Mali. The overall prevalence of cerebral vasculpathy defined by conditional (1.5-1.79 cm/sec) and abnormal TCD (≥ 1.80 cm/sec) in this population is 17.1%. The highest proportion (92.9%) was observed in homozygous SCD patients while the percentage of affected patients was much lower in S/β0thalassemia (4.1%) and in SC (3.1%) patients. No cases were observed in S/β+thalassemia patients. SCD children <9 years old were more susceptible to cerebral vasculopathy complications than those above this age threshold (P<0.001). Low hemoglobin levels and low fetal hemoglobin were associated with an increased risk of cerebral vasculopathy. During the study, 4 of 444 children with normal TCD converted to conditional TCD, while 5 of 68 children with conditional TCD converted to abnormal TCD. This conversion from conditional to abnormal TCD was associated with a mean decrease in Hb value of 0.37g/dL (P=0.002). In conclusion this study shows high prevalence and incidence of cerebral vasculopathy in Malian SCD children. While chronic transfusion programs significantly reduces the risk of stroke in SCD patients with abnormal TCD, at present there are no well articulated strategies to prevent conversion from conditional to abnormal TCD. A more comprehensive approach would hopefully reduce the morbidity and mortality due to cerebral vasculopathy in SCD affected children. Disclosures: No relevant conflicts of interest to declare.

High Percentage of Evanescent Red Cell Antibodies in Patients with Sickle Cell Disease Highlights the Need for a National Antibody Database

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3572-3572
Author(s):  
Marisa B Marques ◽  
Robinna G Lorenz ◽  
Lance A Williams
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Low Frequency ◽  
Red Cell ◽  
Cell Disease ◽  
Positive Antibody ◽  
Clinically Significant ◽  
Antibody Screen ◽  
Transfusion Reactions

Abstract Introduction: From 20 to 50% of patients with sickle cell disease are alloimmunized to red cell antigens from transfusions and/or pregnancies. Pre-transfusion testing (e.g. antibody screening) is essential to avoid hemolytic transfusion reactions from clinically significant antibodies, such as those to Rh, Kell, Duffy and Kidd antigens, among others. Unfortunately, alloantibodies may evanesce over time, becoming undetectable or even leading to a negative antibody screen. Furthermore, antibodies to low frequency antigens in the donor pool, mostly from Caucasians, may not be detected because they are not typically expressed on standard reagent red cells used for testing. Both of these facts contribute to the risk of hemolytic transfusion reactions despite negative pre-transfusion screening. To mitigate this risk, individual transfusion services maintain antibody histories of all patients indefinitely, and must refer to them prior to issuing every unit for transfusion. Patients and Methods: We analyzed data collected from the electronic medical records of every adult (19 and older) patient with sickle cell disease who had one or more positive antibody screen in our institution during a 2-year period from 2013-2015 to determine: 1. antibody specificities; 2. percentage of patients with at least one non-reacting alloantibody; 3. specificities of evanescent antibodies; and 4. number (percentage) of patients with antibodies to low frequency antigens. Results: We identified 71 patients, of which 5 were excluded because they only had a cold-reacting anti-M (n=2), anti-Lewis, a warm autoantibody (WAA), or a High Titer Low Avidity (HTLA) antibody (n=1 each). Thus, 66 patients were included in the analysis (62% females). The age range of the study-group was 19-59 years old (mean ± SD, 33 ± 11 years), similar between males and females (p = 0.43). Males tended to have an antibody screen ordered more often during the study-period, with a trend toward statistical significance (9.4 versus 5.0 times; p = 0.06). The total number of clinically significant alloantibodies was 218 with mean and median number per patient of 3.3 and 3.0, respectively. In addition, 16 patients also had a WAA. Anti-E was the most common alloantibody, followed by anti-C and anti-K; the table shows the antibodies identified at least once in 10% or more of the patients, as well as how often they were not reacting. Of 9 patients with anti-D, 7 were Rh positive, consistent with the propensity of African-Americans to express a D variant. Of note, 30 patients (45%) had antibodies to one or more low frequency antigen such as Cw, V, Vs, Goa, Jsa, Kpa, Lutheran b, Wra, and Ytb; 6 patients (9%) only had alloantibody(ies) to these antigens. Only 12 patients had a positive antibody screen every time they were tested. However, they had significantly fewer tests (average and median of 2, range of 1-6) compared with 54 patients with at least one antibody screen completely negative (average and median of 5 tests, range of 1-30) (p < 0.0001). Table 1.Rh systemKellDuffyKiddMNSsOtherAntibody specificityDCEVGoaKJsaFyaFybJkbSAUSNumber of patients93040147201518912177Percentage of total antibodies4%14%18%6%3%9%7%8%4%5%8%3%Times not reacting516218312121078123Percent evanescent56%53%53%57%43%60%80%56%78%67%71%43%AUS-antibody of unknown specificity; Fya-Duffy a; Fyb-Duffy b; Jkb-Kidd b; Conclusions: Our results demonstrate that 81% of patients with sickle cell disease with a history of red cell alloantibodies had at least one test in which the antibody was not detectable. Delayed hemolytic transfusion reactions are the major risk of evanescent alloantibodies not known to the transfusion service preparing the units. Such reactions may even be fatal, especially if not promptly recognized, since they may be confused with a pain crisis. In addition, we noticed that almost half of the patients had antibodies to low frequency antigens that could have been missed during pre-transfusion testing. Considering that patients with sickle cell disease often suffer from lack of continuity of care, unawareness of their antibody history may lead to life-threatening transfusion reactions. We suggest that a national, or even regional, database of red cell alloimmunization in this patient population is warranted for increased transfusion safety. Disclosures No relevant conflicts of interest to declare.

Prevalence of Sickle Cell Anemia In Eastern India

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4822-4822
Author(s):  
Abhijit Chakraborty ◽  
Jayasri Basak ◽  
Deboshree Majumdar ◽  
Soma Mukhopadhyay ◽  
Sagnik Chakraborty ◽  
...  
Keyword(s):  
Risk Factor ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
West Bengal ◽  
Conflicts Of Interest ◽  
Acute Chest Syndrome ◽  
Red Cell ◽  
Cell Disease ◽  
Cell Counts

Abstract Abstract 4822 Background: Sickle cell disease is an inherited disorder of hemoglobin synthesis. This is due to replacement of Valine for Glutamic Acid in position six of the Beta globin chain of hemoglobin. This genetic alteration yields unstable RBC which lasts for 10–20 days. In stressful conditions the cells become sickle shaped and get lysed. There are about 20 million people with sickle cell disease in India. During January 2009- May2010 camps were held in various parts of West Bengal, Jharkhand, Chattisgarh. Along with various mutations of thalassemia, we also observed sickle cell anemia among them. This triggered our interest to study the spectrum of the sickle mutation co-inheritant with different mutations such as Homozygous Sickle Cell, Sickle Cell-Beta0 Thalassemia, Sickle Cell-Beta+ Thalassemia, Severe β+ thalassemia genes, Moderate β+ thalassemia genes, Mild β+ thalassemia genes Sickle cell-HbE Thalassaemia, Sickle cell-HPFH Thalassaemia, in said part of India. Since Indian patients with SS disease had higher hemoglobin, red cell counts and higher HbF levels and lower HbA2, MCHC, MCV, and reticulocyte counts, hence a high hemoglobin is a risk factor for painful crises and may also be a risk factor for avascular necrosis of the femoral head, proliferative sickle retinopathy, and acute chest syndrome. Methods: We have screened 332 individuals in eastern part of India during the period January 2009- May 2010. 3ml of peripheral blood was collected in EDTA vial from each individual. NESTROFT (Naked Eye Single Tube Red Cell Osmotic Fragility Test) was performed on spot. Then Complete Blood Count was done within 24 hours of collection. HPLC (High Performance Liquid Chromatography) was performed to identify the samples for confirmation. In our observation in case of sickle cell anaemia HbF (Fetal haemoglobin), Hb (haemoglobin), MCV (mean corpuscular volume) values ranges between 0–10 %, ≤7-10g/dl, 65–90fl respectively. ARMS (Amplification Refractory Mutation System) PCR (polymerase chain reaction) was done to confirm the mutation. Result: Conclusion: Of the total samples collected in the camps held at various places of Jharkand, Chattisgarh & West Bengal 87 of them was carriers of sickle cell anemia. There was 7 homozygous (SS), 14 sickle beta, 12 double heterozygous for HPFH (High Persistance of Fetal Hemoglobin) & sickle cell anemia. In conclusion, the manifestations of sickle cell disease are influenced by a variety of other genetic and environmental factors. The occurrence of the disease against different genetic and environmental backgrounds provides experimental models that contribute to understanding the variability in clinical and hematological expression of the disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Identification of Patient-Specific Factors Associated with Alloimmunization in Sickle Cell Disease

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 989-989
Author(s):  
Ryan A Virden ◽  
Kelsey Busken ◽  
Richard Madsen ◽  
Emily Coberly ◽  
Bindu Kanathezhath Sathi
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Laboratory ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Laboratory Data ◽  
Patient Specific ◽  
Continuous Variables ◽  
Cell Disease ◽  
Specific Factors

Abstract Background: Alloimmunization is a frequent complication of red blood cell (RBC) transfusion in sickle cell disease (SCD), arising from disparities between the recipient and donor RBC antigens. This potentially life-threatening complication impacts the utilization of chronic transfusion, a disease-modifying treatment in SCD. Many centers across the country use dedicated donor programs that match SCD recipients to a small group of racially and phenotypically-matched RBC donors in order to minimize exposure to foreign RBC antigens. The pathogenesis of alloimmunization remains an area of active research. Emerging data suggests that a pro-inflammatory state in the recipient plays a role in alloantibody (alloAb) generation. Some SCD patients develop an alloAb after minimal exposure to donor RBC units, whereas others do not. In a subset of these latter patients, multiple exposures to disparate RBC units will not lead to alloAb formation. To further understand this phenomenon, we sought to identify patient-specific factors in SCD that are associated with a higher risk of alloimmunization. Methods: We retrospectively analyzed clinical, laboratory, and transfusion-related data for all pediatric and adult SCD patients treated at the University of Missouri between 2000-2017. Descriptive statistics were expressed for continuous variables. Two-tailed Student's t-tests and Chi-squared analyses were used to determine statistical significance. Results: Of a total of 130 SCD patients identified, 89 patients (58 HbSS, 25 HbSC, and 6 HbSβ0/+ patients) had adequate transfusion, clinical, and laboratory data for inclusion in this study. The overall alloimmunization rate was 28%, with genotype-specific alloimmunization rates of 36% (HbSS), 4% (HbSC), and 50% (HbSβ0/+). Neither age nor gender significantly differed between the alloimmunized and non-alloimmunized groups. Alloimmunized SCD patients received, on average, 4 times more lifetime RBC units as compared to the non-alloimmunized group (264 units vs. 65 units, respectively, p = 0.002). Among all SCD patients, individuals who received more than 5 units per year of life were more likely to become alloimmunized (61% vs. 16%, p = 0.02, Figure 1). The most common alloantibodies identified in our patients were C, E, and Kell (Figure 2). Warm autoantibodies were identified in 36% of all alloimmunized patients versus only 5% of non-alloimmunized patients (p = 0.0001). Lastly, alloimmunization was associated with lower hemoglobin (8.66 ± 1.17 vs. 9.52 ± 1.54, p = 0.01) and higher creatinine (0.71 ± 0.36 vs. 0.56 ± 0.22, p = 0.02) among all SCD patients. In addition, higher LDH (549 ± 180 vs. 386 ± 127, p = 0.01) was observed in pediatric SCD patients who were alloimmunized. Both pediatric and adult SCD patients with the HbSS genotype demonstrated higher creatinine in the alloimmunized group (p = 0.03). An increased incidence of leg ulcers was found to be associated with alloimmunization (12% vs. 0%, p = 0.005, Table 1) amongst all of the clinical variables analyzed. Hydroxyurea therapy was not associated with a decreased prevalence of alloimmunization (Table 2). Conclusions: We identified an association between alloimmunization and higher LDH, lower hemoglobin, and higher creatinine in our SCD patient population. In addition, increased alloimmunization was seen in patients with a higher exposure to RBC units, both cumulatively and on a per life year basis. These data suggest that SCD patients with increased hemolysis or recipients of more than 5 RBC units per life year are associated with a higher risk of developing an alloAb. Larger studies will be required to define a causative relationship between this clinical SCD phenotype and a higher risk of alloimmunization. Disclosures No relevant conflicts of interest to declare.

Red Cell Alloimmunization in Sickle Cell Disease: Benefit of Extended Crossmatching in Adults

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4761-4761 ◽  
Author(s):  
Dianne Pulte ◽  
Julie Kay ◽  
Mary Harach ◽  
Nguyet Le ◽  
Jay H. Herman
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Antibody Formation ◽  
Exchange Transfusion ◽  
Conflicts Of Interest ◽  
High Rate ◽  
Red Cell ◽  
Cell Disease ◽  
Phenotype Matching ◽  
Positive Screen

Abstract Abstract 4761 Background: Patients with sickle cell disease (SCD) receive frequent transfusions and have been observed to have a high rate of transfusion reactions and alloantibody formation after transfusion. Alloimmunization to antigens of the Rh system, Kell, Duffy, MNSs, and Kidd are most common. It has become accepted practice at most sickle cell centers to match for C, E, and Kell antigens in order to prevent alloimmunization. Most studies of the effectiveness of red cell (RBC) phenotype matching have been in pediatric patients and have shown a decrease in alloimmunization beyond those specific antigens that are pre-emptively matched. Leukoreduction (LR) of blood products is known to decrease HLA alloimmunization and may also reduce the risk of RBC antibody formation. It is also unclear whether there is value in continuing phenotype matching beyond the pediatric age and whether new RBC antibodies may be prevented by LR, independent of phenotype matching. Patients with SCD at our institution are routinely matched for C, E, and Kell antigens and given leukoreduced blood. Here, we study our past experience in reducing the frequency of new alloantibody formation. Methods: We reviewed charts of patients with SCD, including sickle cell anemia, sickle/thalassemia, and SC disease, who were transfused at Thomas Jefferson University (TJU) and had documentation of presence or absence of alloantibodies on presentation to our center. Data extracted from chart included patient's age, disease type, known antibodies, and time of first documentation of antibody. Antibodies were considered to be definitely unrelated to transfusion at TJU if they were present before first transfusion at TJU or if a previous screen not showing the antibody in question had been performed and no transfusions given between that screening and the development of the relevant antibody. LR was used routinely at TJU starting in 2003 and was used in selected cases, including many sickle patients, earlier. In 1996, TJU began crossmatching for C, E, and Kell antigens. Results: 68 charts of patients with SCD transfused at least once at TJU were reviewed, including 8 patients undergoing routine exchange transfusion for stroke prevention. Of these, 33 (48.5%) had no alloantibodies detected at any time. Of the remaining 35, 16 had 1 antibody, 8 had 2 antibodies, and 11 had 3 or more antibodies, including 3 patients with 8–10 each. A total of 92 antibodies were identified among these 35 patients, 60 of which were not related to transfusion at TJU. Of the remaining 32 antibodies, the most common antibodies identified were C (5 instances) and E (6 instances). Antibodies to Kell, Fya, and Jkb developed in 3 patients apiece. Two instances each of C, E, and Kell antibodies developed after the initiation of crossmatching for these antigens, but in all but one case, the records suggested that the antibody was most likely developed by transfusion at an outside institution not practicing phenotype matching, but this could not be confirmed (i.e. the patient was not transfused at TJU for >1 year prior to the positive screen appearing, but there were no screens in between to identify whether the antibody became evident ). One instance of C developed after emergency transfusion without extended crossmatch and thus the antibody likely developed from transfusion at TJU. Patients who developed antibodies had a higher number of transfusions than non-immunized patients (median 117 vs 74 units, respectively) and were older (38 vs 35 years, respectively), but neither was statistically significant (p>0.1 in each). Of 8 patients undergoing chronic RBC exchange transfusion, 3 have no alloantibodies, 3 had antibodies that developed from transfusion elsewhere, 1 had a new alloantibody but had prior alloimmunization and 1 developed new alloantibodies at TJU. Conclusions: Our results confirm that C, E, and Kell continue to be the most common antigens leading to alloimmunization in transfused adult SCD patients. A combination of LR and extended phenotype matching appears to be effective in reducing antibody formation compared to historical reports. Our retrospective study has limitations, notably the possibility that patients may have been transfused at other institutions, which may not use phenotype matching or leukoreduced products. Further prospective studies are indicated to aid in determining whether phenotype matching is justified in adult sickle cell patients in the face of growing global LR. Disclosures: No relevant conflicts of interest to declare.

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