scholarly journals Sickle cell disease: Classification of clinical complications and approaches to preventive and therapeutic management

2018 ◽  
Vol 68 (2-3) ◽  
pp. 105-128 ◽  
Author(s):  
Samir K. Ballas
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Disease Classification ◽  
Therapeutic Management ◽  
Cell Disease ◽  
Clinical Complications

Chronic red blood cell exchange to prevent clinical complications in sickle cell disease

2005 ◽  
Vol 32 (3) ◽  
pp. 315-321 ◽  
Author(s):  
Sergio Cabibbo ◽  
Carmelo Fidone ◽  
Giovanni Garozzo ◽  
Agostino Antolino ◽  
Giovanna Oriella Manenti ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Cell Disease ◽  
Clinical Complications

scholarly journals New classification of peripheral retinal vascular changes in sickle cell disease.

1994 ◽  
Vol 78 (9) ◽  
pp. 681-689 ◽  
Author(s):  
A D Penman ◽  
J F Talbot ◽  
E L Chuang ◽  
P Thomas ◽  
G R Serjeant ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Vascular Changes ◽  
Cell Disease ◽  
New Classification

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.

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.

Clinical Complications in Adult Patients with Sickle Cell Anemia and β-Thalassemia-Sickle Cell Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4767-4767
Author(s):  
Giovanna Graziadei ◽  
Alessia Marcon ◽  
Martina Soldarini ◽  
Ilaria Gandolfi ◽  
Luisa Ronzoni ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Acute Chest Syndrome ◽  
P Value ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Clinical Complications ◽  
Significant Difference ◽  
The Mean

Abstract Abstract 4767 Background. Sickle-Cell Disease (SCD) is one of the most common severe monogenic inherited disorders worldwide, due to hemoglobin S (HbS), with reduced affinity for the oxygen. HbS polymerization, leading to erythrocyte rigidity, vaso-occlusion and hemolytic anemia, is central in the pathophysiology and crucial for the clinical outcome. The term SCD refers to Sickle Cell Anemia (SCA) due to homozygosis for βS allele, HbS/β-thalassemia (T-SCD) due to compound of β-thal and βS allele, and HbSC disease, owing to the coinheritance of βS and βcalleles. SCD is a multiorgan disease characterized by recurrent acute events and progressive organ damage, worsening during the life. Aims. This is a retrospective monocentric study aimed to assess and compare the clinical complications among 59 adult SCD patients, followed at the Hereditary Anemia Centre of the Foundation IRCCS “Ca Granda” Ospedale Maggiore Policlinico, in Milan, Italy. Methods. Mutation analysis of the b globin gene was established by direct DNA sequencing on the ABI Prism 310 genetic analyzer. Clinical and hematological features were evaluated by routine tests and physical examination, with special attention to the erythropoiesis stress parameters as LDH values and extramedullary erythropoietic (EE) masses. Results. Fifty-nine adult SCD patients, 16 SCA and 43 T-SCD, were evaluated. In T-SCD patients detected b-mutations were severe (b°) in 69.8%, and moderate or mild (b+-b++) in 30.2%. The mean age of SCA patients was 36±9 and 41±11 years for T-SCD patients. For both groups the mean follow-up was 20±6 years, while the mean age at the presentation in our Centre was 32±8 years in SCA patients and 31±10 years in T-SCD ones. Five out of 16 (31.2%) SCA patients and 16/43 (37.2%) T-SCD patients were male. HbF mean levels were 6.9±5.1% and 10.1±7.2%, respectively in SCA and T-SCD group; surprisingly Hb mean levels were lower in SCA (9.3±1.3 g/dl) than in T-SCD (9.9±1.4 g/dl) patients. Comparing SCA and T-SCD, there was statistically significant difference in splenic features: splenectomy was performed in 2/16 (12.5%) SCA patients vs 21/43 (48.8%) T-SCD patients (p-value < 0.01). Splenomegaly was absent in SCA, while was detected in 11/22 (50%) T-SCD (p-value < 0.0001); all SCA patients had functional asplenia, not observed in T-SCD patients; splenic infarctions were absent in SCA patients and were detected in 7/22 (31.8%) T-SCD patients, of whom 5 had splenomegaly and 2 had normal spleen size (pvalue <0.001). On the other side, there was not statistically significant difference in the prevalence of stroke, acute chest syndrome (ACS), bone pain crisis, sepsis, leg ulcers and priapism. However, we observed some clinical differences, even if not statistically significant. Cholecistectomy was performed in 4/16 (25%) SCA patients vs 17/43 (39.5%) T-SCD patients, and gallstones were detected respectively in 5/12 (41.7%) and in 14/26 (53.8%) of SCA and T-SCD patients. Thrombotic events were absent in SCA patients, compared to 4/43 (9.3%) T-SCD patients. Furthermore, we detected EE in 3/16 (18.6%) SCA and in 3/43 (7%) T-SCD, all carrying b° thal mutations. We underlie that Hb levels and LDH values were higher in SCA than in T-SCD patients (823±295 vs 689±209 U/L). About the treatment, 14/16 (87.5%) SCA and 31/43 (72%) T-SCD underwent to top-up transfusion; 5/43 (11.6%) T-SCD were regularly transfused. Seven out of 16 (43.8%) SCA and 18/43 (41.8%) T-SCD patients were treated with Hydroxycarbamide (HU). Criteria for transfusion therapy were: painful crisis not responsive to HU, major clinical complications, such as stroke or ACS, extramedullary erythropoietic masses associated with high LDH levels and low Hb values. Conclusions. These data suggest that SCA and T-SCD patients have similar clinical course. Splenomegaly is present only in T-SCD patients, probably due to the increased amount of extravascular hemolysis. Surprisingly, SCA patients showed EE and lower Hb levels with higher LDH values compared to T-SCD ones. This could be related to the prevalence of intravascular hemolysis, that can lead to erythropoietic stress in SCA, even if tissues are better oxygenated in these patients because of biochemical characteristic of HbS in terms of decreased oxygen affinity. These observations could be important to evaluate transfusion and HU treatment. Disclosures: Cappellini: Novartis: Research Funding.

Daytime and Nocturnal Hypoxemia Are Related With Hemolysis In Adults With Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2229-2229
Author(s):  
Ana Carolina Cabanas-Pedro ◽  
Sandra Satiko Matsuda, ◽  
Suely Roizenblatt ◽  
Joao Roberto Reinfelderon ◽  
Sergio Tufik ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Cell Disease ◽  
Clinical Complications ◽  
Nocturnal Hypoxemia ◽  
Previous Stroke ◽  
The Mean ◽  
De Medicina

Abstract Introduction Different studies had shown that nocturnal hypoxemia is associated with clinical complications in children with sickle cell disease (SCD), and, more recently, iron availability was related with nocturnal oxymetry in these children. However, there are few studies about this subject in adults with SCD, despite the fact that nocturnal hypoxemia occurred in 60% of the patients. We aimed to evaluate daytime and overnight hypoxia and its influence on clinical and laboratorial parameters in adults with SCD. Patients and Methods 82 steady state patients with SCD followed at Anemia Out-Patient Clinic from Escola Paulista de Medicina/UNIFESP were invited to this study. This study was approved by Ethical Committee, and all patients agreed in participate. The daytime oximetry (SpO2) utilized was the mean of at least 3 measurements by pulse oximeter during regular appointments at the out-patient clinic. The nocturnal oximetry data (basal SpO2 and mean nocturnal SpO2) were obtained during polysomnography (PSG). Besides clinical evaluation, routine laboratory tests performed near the realization of the PSG were analyzed. The data was analyzed by parametric and non-parametric tests, with α=5%. Results The median (range) age was 28 (18-69) years, and 44 (54%) were female. Moderate sleep apnea was diagnosed in 11% of the patients. The mean of SpO2 obtained for each measurement was: daytime SpO2: 95.1±4.3, basal SpO2: 94.3±3.5, and mean nocturnal SpO2: 93.3±3.6; with statistical significance between daytime and basal SpO2 (X2=17.0; p<0.001) and between daytime and mean nocturnal SpO2 (X2=10.3; p=0.001). The percentage of patients with hypoxemia (SpO2 ≤ 90%) varied according with the measurement: 14.1% at daytime SpO2, 13.7% at basal SpO2, and 20.0% at mean nocturnal SpO2. However, 55% of the patients achieved hypoxemia level during PSG. Association between daytime SpO2 and previous stroke was observed (X2=4.0; p=0.04). Patients with daytime and basal SpO2 ≤ 90% had higher lactate dehydrogenase (LDH) (634.3±114.9 and 538.0±198.3) compared to the ones with SpO2>90% (384.0±171.6 and 375.7±171.9; p<0.001 and p=0.02, respectively). Reticulocyte count was more elevated in patients with SpO2 ≤ 90% (daytime SpO2: 277,639.2±96,108.4; basal SpO2: 290,722.9±87,791.2 and mean nocturnal SpO2: 260,582.1±83,532.8) when compared to the ones with SpO2 >90% (185,537.3±90,445.7; 188,432.2±101,277.1 and 189,194.1±104,478.8; p=0.01; p=0.01 and p=0.03, respectively). No correlation was found within iron and SpO2. Conclusion Daytime and nocturnal hypoxemia showed effect on hemolytic markers in adults with SCD. Daytime SpO2 presented an association with previous stroke and considering that it was also observed an association between daytime and nocturnal SpO2, we suggest that daytime SpO2determination should be monitored in each appointment and can be used as a predictor of SCD severity Supported by CAPES/SUS and AFIP. Disclosures: No relevant conflicts of interest to declare.

Cochlear and Neural Diseases: Classification and Oto-Audiologic Correlations

1974 ◽  
Vol 83 (3) ◽  
pp. 304-311 ◽  
Author(s):  
Richard E. Marcus
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Alport's Syndrome ◽  
Clinical Classification ◽  
Cell Disease ◽  
Alport’S Syndrome ◽  
Pathologic Findings ◽  
Definition Of ◽  
Neural Diseases

An extended clinical classification of cochlear and neural disease is presented along with an anatomical definition of corresponding cochlear and neural compartments. The clinical classification has three categories: prenatal, neonatal, and delayed, with each subdivided into genetic and acquired groups. The cochlear and neural compartments are arbitrarily divided at the habenula perforata with the unmyelinated dendrites considered part of the cochlear compartment. This allows a clinical reconciliation of cochlear and neural disease with oto-audiologic and pathologic findings. Patients are presented with Alport's syndrome, meningitis and obliterative labyrinthitis, mumps, diabetes and sickle cell disease to illustrate the clinical classification. Pathologic correlations are postulated in each of the patients.

scholarly journals Fragment D-dimer levels: an objective marker of vaso-occlusive crisis and other complications of sickle cell disease

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 317-319 ◽  
Author(s):  
DV Devine ◽  
TR Kinney ◽  
PF Thomas ◽  
WF Rosse ◽  
CS Greenberg
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Latex Agglutination ◽  
Cell Disease ◽  
Aseptic Necrosis ◽  
Clinical Complications ◽  
Asymptomatic Patients ◽  
Coagulation Tests ◽  
The Relationship ◽  
D Dimer

Abstract Although abnormalities in coagulation tests have been reported during vaso-occlusive crises in patients with sickle cell disease, objective, readily performed laboratory tests that document the occurrence of this complication have not been available. We examined the relationship between fibrin D-dimer levels and the occurrence of complications in patients with sickle cell disease, using a commercially available latex bead agglutination assay. The patients were either asymptomatic, hospitalized for vaso-occlusive crisis, or had other complications of sickle cell disease including leg ulcers, chronic cholecystitis, aseptic necrosis, joint pain and infection. Fifty-seven percent of 187 samples on 96 patients had elevated levels of fibrin D-dimer. Ninety percent of 75 samples from asymptomatic patients were negative for fibrin D-dimer (less than 1 microgram/ml) but 97% of 29 samples from patients with vaso-occlusive crisis and 85% of 83 samples from patients with other complications of sickle cell disease were positive. In serial studies, worsening or amelioration in clinical complications were reflected in increasing or decreasing levels of fibrin D-dimer, respectively. The molecular species of fibrin identified by the latex agglutination test was shown to be fragment D-dimer by successive immunoprecipitation and protein blot analysis. We conclude that the complications of sickle cell disease, including vaso-occlusive crisis, result in the production of fibrin D-dimer, and its detection may be used as a marker for the presence of the complication.

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