Th17/Treg Imbalance in Sickle Cell Disease and Hydroxyurea Therapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1050-1050
Author(s):  
Simone Gilli ◽  
Fernando V Pericole ◽  
Luis Gustavo Fernandes ◽  
Karina A. R. Ribeiro ◽  
Lilian Castilho ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Th2 Cells ◽  
Control Group ◽  
Healthy Controls ◽  
Cell Disease ◽  
T Cell Dysfunction ◽  
Th17 Differentiation

Abstract Abstract 1050 Background: Tregs and proinflammatory Th17 cells have been described as two distinct subsets from Th1 and Th2 cells and have opposite effects in autoimmunity and inflammation. Th17/Treg balance controls inflammation and is important in the pathogenesis of autoimmune, infectious and chronic diseases. In view of growing evidence linking sickle cell disease (SS) and chronic inflammation and the potential anti-inflammatory role of Tregs cells, we hypothesized that SS is associated with decreased Treg subpopulation and consequent T cell dysfunction. Furthermore, the effects of hydroxyurea (HU) in this balance are not understood. To assess whether the Th17/Treg balance is impaired in patients with sickle cell disease, we investigated the peripheral blood Th17 and Treg frequencies and the expression of TGFβ1 and RORγT, a master regulator of Th17 differentiation, in sickle cell patients under HU therapy (SS-HU) and without HU (SSw/oHU). Methods. Thirty-eight patients with steady-state sickle cell disease (mean age 43 ± 10.5 yo; range 19–57 yo; 21 female/17 male), 19 SS-HU, 19 SSw/oHU and 20 healthy blood donors were evaluated. Tregs and Th17 quantification was performed by flow cytometry analysis and the expression of TGFβ1 and RORγT by q-PCR. Results. We found significant decrease in the Treg frequency (Foxp3+CD25+CD4+ population) comparing total SS patients and healthy controls (p=0.001) and this difference was more expressive between SS-HU and healthy controls (P=0.0006). Moreover, we found statistically increase of Th17 in SS-HU (p=0.02) and in SSw/oHU (p=0.01), comparing both with healthy controls. The TGFβ1 expression was increased in SS-HU (p=0.04) and SSw/oHU patients (p=0.01) when compared to control group. Interestingly, RORγT expression was significantly elevated only in SSw/oHU vs controls (p=0.03). Conclusion: Our results demonstrated a numerical imbalance of Th17/Treg in the peripheral blood of patients with SS disease. HU has no role mediating Th17/Treg plasticity and even SS patients under HU therapy remains Treg depleted. However, HU is able to modulated RORγT, corroborating the importance of other regulating factors during Th17 differentiation. Moreover, the higher expression of TGFβ1 may be an important positive instructive signal for Th17 differentiation. Th17/Treg imbalance might impact the disease presentation and phenotype and HU therapy may be involved in this issue. Disclosures: No relevant conflicts of interest to declare.

Measurement of Urine Pyridinoline and Deoxypyridinoline as Markers of Increased Bone Degradation in Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2572-2572
Author(s):  
Erfan Nur ◽  
Willem Mairuhu ◽  
Dees P. Brandjes ◽  
Ton van Zanten ◽  
Bart J. Biemond ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Bone Resorption ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Healthy Controls ◽  
Cell Disease ◽  
Skeletal Involvement ◽  
Asymptomatic Patients ◽  
Bone Degradation ◽  
Painful Crisis

Abstract Abstract 2572 Poster Board II-549 Introduction: Sickle cell disease (SCD) is commonly manifested through skeletal involvement. Besides the characteristic acute musculoskeletal pain, SCD is also associated with chronic skeletal complications such as osteopenia and osteoporosis. During bone resorption, the collagen cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are released into circulation with subsequent urinary excretion. Measurements of urinary PYD and DPD could serve as valuable tools in detecting osteoporosis in the follow-up of SCD patients but perhaps also in determining the severity of bone infarction during painful crises. Therefore we compared urinary concentrations of PYD and DPD of SCD patients during asymptomatic state and painful crisis with those of race- and age-matched healthy controls. Methods: Urinary concentrations of PYD and DPD, adjusted for urine creatinine, were measured in SCD patients both during asymptomatic state (n=38) and painful crisis (n=27) and healthy controls with normal HbA hemoglobin (n=25) using high performance liquid chromatography (HPLC). Results: PYD and DPD concentrations were higher in asymptomatic SCD patients compared to controls ((54.8 (41.5–68.6) vs. 44.1 (37.7–49.9),P=0.005 and 11.6 (9.3–15.2) vs. 8.5 (6.8–10.4),P=0.004 respectively), with further increments during painful crisis (63.3 (51.8–76.0),P=0.041 and 15.3(13.0–21.5),P=0.003 respectively). In the asymptomatic patients levels of PYD and DPD were significantly correlated to the degree of hemolysis. Conclusion: In sickle cell patients bone resorption is increased and significantly correlated to the degree of hemolysis, compatible with their susceptibility to osteopenia and osteoporosis. Measurement of pyridinoline and deoxypyridinoline could have additional value as biomarkers of osteoporosis in SCD. During painful crises a further increment in bone degradation was observed. Disclosures: No relevant conflicts of interest to declare.

Implementation of a European Cohort to Follow Sickle Cell Children and Adults Treated with Hydroxycarbamide

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 564-564
Author(s):  
Mariane De Montalembert ◽  
Frédéric Galacteros ◽  
Jean Antoine Ribeil ◽  
Uwe Kordes ◽  
Jean Benoit Arlet ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Safety Profile ◽  
Conflicts Of Interest ◽  
Subcutaneous Tissue ◽  
Acute Chest Syndrome ◽  
Control Group ◽  
Cell Disease ◽  
Skin Reactions ◽  
Number Of Patients

Abstract Hydroxycarbamide (HU) is a myelosuppressive drug marketed since 1968 for the treatment of hematological cancer, and authorized since 2007 in Europe as orphan medicinal product for the prevention of recurrent vaso-occlusive crises including acute chest syndrome in adults and children older than 2 years with sickle cell disease (SCD). ESCORT-HU (European Sickle Cell Disease Cohort – Hydroxyurea) is a multicenter prospective non interventional study implemented in Europe to collect more information about the safety profile of HU and morbi-mortality in SCD patients treated with HU. The study responds to EMA (European Medicines Agency) request and has been approved by the Ethical of Necker Enfants Malades Hospital (Paris, France).The ongoing study involves the largest number so far of patients with SCD treated with HU. Primary endpoints of ESCORT HU are to determine frequency of adverse events, and possible consequent changes of HU treatment. Secondary endpoints are to evaluate morbi-mortality of the disease although in the absence of control group. From June 2008 to June 2014, 483 patients (255 females; 228 males) were enrolled from 3 European countries, Greece (24%), Germany (19%), and France (56%). 67% patients were adults, median aged 37.35 yrs (17-83.5) and 33% were children, median aged 11.06 yrs (2.6-16.9). genotypes were HbS/HbS in 71.4% cases, and compound heterozygotous HbS/β-thalassemia in 22.8 % (Table 1). 137 (28.4%) patients experienced 421 events (Table 2). 132 (32.2%) of these events may be attributed to HU. The safety profile is roughly similar in children and adults. As expected the most frequent side effects were firstly blood disorders (n=86 events, 42.4%) such as neutropenia or thrombocytopenia. In all cases, these cytopenias were rapidly resolved with the transitory stop of HU. 71 events related to skin and subcutaneous tissue disorders were observed, mostly cutaneous dryness, skin reactions, alopecia and nails or skin pigmentation; 4 patients had a leg ulcer (34.8%). Most of these events are ongoing or stabilized despit the decrease of HU. No secondary cancer has been reported until now. Even if HU is an old drug with a relatively well-known safety profile, some uncertainties remain in terms of long-term safety as well as tolerance in the youngest people. The main interest of ESCORT HU is to offer the possibility of safety surveillance of hydroxycarbamide in European sickle cell patients. Table 1 Demographic data Adults Children < 17 years old Total Number of patients 322 (67%) 161 (33%) 483 Females/Males 183/139 72/89 255/228 Median age (yrs) (range) 37.35 (17-83.5) 11.06 (2.6-16.9) 28.58 Genotype SS 206 (64%) 139 (86.3%) 345 (71.4%) SC 1 (0.3%) 3 (1.86%) 4 (0.8%) Sβ0 51 (15.8%) 11 (6.8%) 62 (12.8%) Sβ+ 46 (14.2%) 2 (1.2%) 48 (9.9%) Other 18 (5.5%) 6 (3.7%) 24 (4.9%) Treatment with HU before enrollment in ESCORT HU No of pts 232 83 315 (65%) Median duration (range) of HU treatment before ESCORT HU 8.2 yrs (0.5 ans-24 yrs) 3. 1 yrs ( 71 days – 8.9 yrs) 6.85 (71 days-24 years)] HU ESCORT Daily mean dose (mg/kg/d) 16.11 ± 4.79 19.63 ± 4.69 17.32 ± 4.94 Abstract 564. Table 2 The most frequent events of hydroxycarbamide in the two populations of SCD patients ADULTS CHILDREN No ofGerman(%) No of adults No ofEpisodes(%) No of children Total(% /411) Events Related to HU treatment (Siklos®)(%**) Blood and lymphatic system disorders (%) 32 (17.7) 22 54 (31.03) 28 86 (20.9) 56 (65.1) Skin and subcutaneous tissue disorders (%) 42 (23.2) 28 29 (16.7) 19 71 (17.3) 46 (64.8) Nervous system disorders Headache (24), Dizziness/vertigo (14), 32 (17.7) 23 12(6.9) 10 44 (10.7) 11 (25) Gastrointestinal disorders Nausea (14), diarrhea (8), other (14) 20 (11) 17 23 (13.2) 16 43 (10.4) 7 (16.3) Metabolic and nutrition disorders: vit D deficiency (17), weight gain (5) 13 (7) 11 18 (18.3) 18 36 (8.75) 4 (11.1) Fever 11 (6) 10 12(6.9) 7 23 (5.6) 1 (4.3) Cardiac disorders (hypertension, bradycardia, chest pain, cardiomegaly) 4 4 2 2 6 1 (16.6) General disorders : fatigue 5 5 0 0 5 0 Hepatobiliary disorders 2 2 0 0 2 0 Neoplasms benign, malignant and unspecified (incl. cysts and polyps) Harmatoma, benign vulvar sebaceous cyst 2 2 0 0 2 0 Renal & urinary disorders 2 2 0 0 2 0 Reproductive system and breast disorders 3 3 0 0 3 0 Other 13 13 21 14 34 6 (17.1%) 181 80 /181(24.8%) 174 57 / 174(35.4%) 411 132/411 (32.2%) ** compared to the total number of “system organ class” events Disclosures No relevant conflicts of interest to declare.

scholarly journals Expression Pattern of CD55 and CD59 on Red Blood Cells in Sickle Cell Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4815-4815
Author(s):  
Salah A. Al Humood ◽  
Lama A. Al-Faris ◽  
Monera Al-Rukhayes
Keyword(s):  
Sickle Cell Disease ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
Conflicts Of Interest ◽  
Flow Cytometric Analysis ◽  
Healthy Controls ◽  
Cell Disease ◽  
Altered Expression ◽  
Cd59 Expression

Abstract Background: Altered expression of glycosylphosphatidylinositol (GPI)-anchored proteins, might result in increased susceptibility of red blood cells (RBCs) to complement-mediated lysis. Limited information is available on the pattern of CD55 and CD59 expression on RBCs of sickle cell disease (SCD) patients. Methods: Flow cytometric analysis was performed on RBCs from 71 adult SCD patients and 53 healthy controls, using the commercial REDQUANT kit. Results: CD59 deficiency was significantly higher among SCD patients than among healthy controls. The proportions of CD55-deficient and CD59-deficient RBCs from SCD patients were significantly higher when compared with those from healthy controls (0.17 vs. 0.09 and 2.1 vs. 1.2, respectively). The MFI of CD55 and CD59 expression on RBCs in SCD was significantly reduced when compared to the expression healthy controls (5.2 vs. 6.4 and 19.4 vs 20.3, respectively). The pattern of CD55 and CD59 expression was not correlated with anemia, biomarkers of hemolysis, erythropoietin level or other pro-inflammatory markers. Conclusions: There is an altered pattern of CD55 and CD59 expression on RBCs of SCD Patients; however, it does not seem to play a causal role in the pathophysiology of anemia, and is unlikely to be influenced by the level of erythropoietin or other inflammatory mediators. Disclosures No relevant conflicts of interest to declare.

scholarly journals Complications in Pregnancy of Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-33
Author(s):  
Avani Singh ◽  
Conner Olsen ◽  
Xu Zhang ◽  
Robert E. Molokie
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Mode Of Delivery ◽  
Acute Chest Syndrome ◽  
Control Group ◽  
Thromboembolic Events ◽  
Cell Disease ◽  
Fetal Outcomes ◽  
Systemic Complications

Sickle cell disease (SCD) has many systemic complications including vaso-occlusive crises (VOC), stroke and increased mortality. However, as a result of advances in the care of children with SCD, over 90% of those born with SCD in the US live until they are at least 20 years of age. As survival improves, more women with SCD are able to have children. Through improvements in the management of pregnancy, the majority of women with SCD can have an uncomplicated birth though they do have a high incidence of medical and pregnancy complications compared to those women with normal phenotype. While current literature regarding pregnancy in SCD often compares sickle cell patients to normal hemoglobin phenotype patients, more research is needed comparing individuals with SCD. This study seeks to examine the number of vaso-occlusive crises, acute chest syndrome (ACS) episodes and thromboembolic events in pregnant patients with SCD, comparing during pregnancy, the 12 months before and the 12 months after pregnancy. A 10-year retrospective study was conducted at University of Illinois Health System (UIH) and included women over the age of 18 with sickle cell disease and pregnancy. These patients followed primarily at UIH for both their sickle cell and obstetric care. The query included 208 pregnancies and 177 patients. The primary endpoint was to compare the number of VOC, ACS, and thromboembolic events in patients with sickle cell disease during 9 months of pregnancy, the 12 months prior to their pregnancy and the 12 months after their pregnancy. Secondary endpoints include prophylactic, simple, and exchange transfusions throughout the pregnancy, mode of delivery, obstetric complications (preeclampsia, eclampsia, mortality), and fetal complications (IUGR, Apgar scores, mortality). Of 208 pregnancies from the initial query, 121 met inclusion criteria for the study. 87 of the 208 pregnancies met exclusion criteria due to other hemoglobin genotypes, delivery outside the study timeframe, delivery at outside hospital, or encounters for ectopic pregnancies, spontaneous or elective abortions. Paired comparisons between pregnancy, 12 months before the pregnancy, and 12 months after the pregnancy were carried out using non-parametric method (Wilcoxon's test) or generalized mixed effects models. Results demonstrated a statistically significant increase in VOC and ACS during pregnancy, compared to the 12 months prior and 12 months after pregnancy, as demonstrated in Table 2. Thromboembolic events had a slight trend of increase during pregnancy compared to the period before or after. These results were adjusted for age at delivery and restricted to SS genotype. VOC and severe genotype were found to associate with maternal and fetal outcomes such as C-section (p=0.04), transfusion requirement at delivery (p=0.007), low birth weight (p=0.008), and preterm delivery (p=0.02). Our findings demonstrate a definitive and statistically significant increase in VOC and ACS during pregnancy compared to the 12 months before or after pregnancy among women with SCD. This unique study compares patients with SCD to themselves longitudinally through time, utilizing a superior control group. Although this increase in VOC and ACS has been observed previously, prior studies compared pregnant patients with SCD to other patients with SCD, or to controls with normal hemoglobin. As hypothesized, thromboembolic events had a slight trend towards increasing during pregnancy, however this comparison was not statistically significant. Although prior data has shown prophylactic transfusions to decrease VOC in pregnant women with SCD, prophylactic transfusions were rarely utilized in this study group. These results demonstrate a definitive increase in VOC in pregnant individuals with SCD, and additionally affecting maternal and neonatal outcomes. Based on this study, decreasing rates of VOC during pregnancy may improve maternal and fetal outcomes. This may be achieved with prophylactic transfusions; however additional studies must be conducted to improve care in this patient population. This study will also allow us to further investigate additional characteristics that change during this timeline during pregnancy. This offers new opportunities to institute individualized preventive strategies, expanding the role of personalized medicine in the care of sickle cell patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Frequency of Thrombotic Events in Hospitalized Patients with Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Susumu Inoue ◽  
Christina Anagonye
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Medical Center ◽  
Thrombotic Event ◽  
Beta Thalassemia ◽  
Control Group ◽  
Cell Disease ◽  
Very High Frequency ◽  
Thrombotic Risk

Background Thrombosis is one of the most common complications described in patients with sickle cell disease. However, little is known about the prevalence, variety and severity of thrombus particularly in sickle cell patients hospitalized with vaso-occlusive crisis. Methods We made a retrospective chart review of patients (age 21 years or older) admitted with sickle cell disease at Hurley Medical Center (Flint, Michigan) and was diagnosed with a thrombotic event between April 2012 and April 2020. To obtain a logistic model, we identified all patients with the the final discharge diagnosis of thrombosis (ICD-9 or ICD-10 code indicating any thrombosis, such as DVT, arterial thrombosis, catheter-related thrombus, pulmonary embolism, and stroke), combined with the diagnosis of sickle cell disease. Findings 37/137 (27%) sickle cell patients were found to have had at least one thrombotic event during their hospitalization. As predicted, patients with sickle cell disease appeared to have very high frequency of thrombotic complications, though we lack a control group to compare with. Genotypes of sickle cell disease was also measured in this study. Patients with the Hb-SS disease had a much higher rate of this complication(25/68=37%) compared with those with Hb SC disease patients (12/49=24%). There were no thrombotic events reported in patients with Hb S/beta thalassemia+, or 0 patients or in patients with Hb SS with HPFH. Interpretation The risk of a thromboembolic event in patients with SCD is high, Sickle cell anemia is a procoagulant condition, which is a risk factor for thrombosis. More research is required to determine if preventive modalities could reduce thrombotic risk. Disclosures No relevant conflicts of interest to declare.

Dominant Role for SDF-1 in the Vasculo-Angiogenesis Phenotype in Children with Sickle Cell Disease.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1432-1432
Author(s):  
Beatrice E Gee ◽  
Jerry M Manlove-Simmons ◽  
Yao Huang ◽  
Nana Wilson ◽  
Jonathan Stiles ◽  
...  
Keyword(s):  
Growth Factors ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Vascular Injury ◽  
Peripheral Blood ◽  
Plasma Concentrations ◽  
Control Group ◽  
Cell Disease ◽  
Angiogenic Growth Factors ◽  
Colony Number

Abstract BACKGROUND: Vasculogenesis is critically important to restoring and maintaining vascular homeostasis in patients who have sickle cell disease. Emerging evidence indicates vasculo-angiogenesis is a complex process involving recruitment of endothelial progenitor cells (EPCs) from the bone marrow and homing of EPCs to sites of vascular injury. Both recruitment and homing of EPCs are intimately regulated by cytokines and growth factors that are released in response to vascular insult. Hitherto, the phenotype of growth factors and cytokines intimately involved in EPC recruitment and homing in patients who have sickle cell disease remains poorly understood. METHODS: A total of 50 children aged 6–18 years were studied, 30 with Hemoglobin SS, including 11 on chronic red blood cell transfusions, and 20 with normal hemoglobin. We measured plasma concentrations of angiogenesis growth factors/cytokines using a multiplex assay, which permitted analysis of nine factors concurrently, and determined the number and phenotype of EPC colonies derived from peripheral blood samples. RESULTS: Plasma concentrations of stromal derived growth factor (SDF-1, 1.7-fold), angiopoietin-2 (Ang-2, 2-fold) and erythropoietin (7-fold) were significantly elevated (p&lt;0.001) in children with sickle cell disease compared to control subjects. On the contrary, plasma leptin was significantly lower (2-fold, p&lt;0.001) in the sickle cell disease group, while no significant differences were found for several other angiogenic growth factors including VEGF, HGF, IL-8, PGF and PDGF between children with sickle cell disease and the control group. Peripheral blood-derived EPC colonies were significantly higher (almost 3-fold) in patients who have sickle cell disease compared to the control group. Interestingly, EPC colony number was lower in sickle cell patients on chronic transfusion therapy compared to those who were not on chronic transfusion. There were significant correlations between EPC colony number and plasma concentrations of SDF-1 (r=0.65, p&lt;0.001) and Ang-2 (r=0.36, p&lt;0.05), but no correlation between EPC colony number and plasma erythropoietin and leptin. CONCLUSION: These data demonstrate for the first time enhanced vasculogenic potential in patients with sickle cell disease at steady-state. SDF-1 enhances the homing of EPCs and is highly expressed in ischemic tissues. The association of elevated SDF-1 and Ang-2 levels with EPC colony number is consistent with the hypothesis that sickle cell disease causes ongoing ischemic vascular injury. SDF-1 may be potentially used as a marker for vascular injury and a therapeutic target that can be developed to augment vascular repair in sickle cell disease.

Human Platelet Alloantigens (HPA)1, HPA2 and HPA3 SNPs in Tunisian Sickle Cell Disease Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4852-4852
Author(s):  
Adel Driss ◽  
Karima Kacem ◽  
Nana Wilson ◽  
Jacqueline Hibbert ◽  
Tom Adamkiewicz ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Human Platelet ◽  
Disease Onset ◽  
Acute Chest Syndrome ◽  
Healthy Controls ◽  
Cell Disease ◽  
Blood Samples ◽  
Test Kit

Abstract Abstract 4852 Sickle Cell Disease (SCD) is a complex disease with various complications such as stroke, vaso-occlusive crisis (VOC), acute chest syndrome and leg ulcers. Sickle cell anemia (SCA; homozygous hemoglobin SS) is the most common form of SCD. Genetic variations and/or environmental modifiers may modulate clinical presentation of SCD. Few studies have examined hemoglobinopathies in Tunisia, North Africa. However, recently, frequencies of beta-thalassemia and sickle cell trait were estimated at 2.21% and 1.89%, respectively (Fattoum, 2006). In order to identify genetic factors that may predispose patients to SCD complications in this population, a pilot case control study was designed to assess polymorphisms in Human Platelet Antigen (HPA) Genes. HPA polymorphisms were recently associated with severe coronary artery disease in the general population in Tunisia (Abboud et al, 2010) and VOC presentation in SCA patients from Bahrain (Al-Subaie et al, 2009). We present here a study conducted in collaboration with the Department of Clinical Hematology at the Aziza Othmana Hospital in Tunis (Tunisia). The National Medical Ethics committee of Tunisia as well as the Institutional Review Board (IRB) of Morehouse School of Medicine (MSM) approved the study. Blood samples, clinical history and DNA samples were collected from SCD adult patients and healthy controls after informed consent. Previously validated questionnaires for genetic risks in patients with SCD (courtesy of Dr Telen, Duke University) were adapted to French. The Helena test kit was used to generate hemoglobin variant data in conjunction with cellulose acetate electrophoresis. Blood samples were collected in EDTA vacutainer tubes and genomic DNA was isolated,stored at −80°C and then shipped to MSM. Single nucleotide polymorphisms, SNPs (Table 1) were genotyped using PCR-RFLPs and compared with different clinical sub-phenotypes such as, onset age, strokes, cardiac problems, splenectomies, etc. as defined in the questionnaire. Pearson Chi-Square was used for comparison and a P<0.05 value was considered significant. A total of 98 DNA samples were collected and 54 questionnaires were filled (Table 2). Age of patients at time of sample collection ranged from 19 to 61 (n = 49) with a mean ± sd (standard deviation) of 29 ± 7. The reported age at onset ranged from 1 to 30 (n = 44) with a mean ± sd of 12 ± 9. No significant differences were found in the HPA alleles and genotype frequencies in SCD versus healthy controls. There was significant association between HPA1 polymorphism with patient defined cardiac problems in all SCD patients (P = 0.002) as well as in the SS sub-group separately (P = 0.01). There was significant association between HPA1 and reported age of onset in SCD patients (P = 0.05) as well as in the non-SS sub-group alone (P = 0.04). The HPA1 variant was linked to self-reported age of disease onset and heart complications in adult SCD patients in Tunisia. This present study is one of the first genetic studies in a seldom-studied group of Tunisian adult SCD patients. These results show that identification of biomarkers of SCD disease severity may be possible using a validated self-reporting instrument. This kind of approach could help to improve early diagnosis of at risk patients and enable development of early interventions.Table 1:SNPs screened.SymbolRs#Ch.Gene (GeneID)MutationPeptide changeRestriction Enz.HPA1rs591817ITGB3 (3690)196 T>CLeu33ProMspIHPA2rs606517GP1BA (2811)524 C>TMet145ThrSfaNIHPA3rs591117ITGA2B (3674)2622 T>GIle843SerFokITable 2:Tunisian cohort collection took place from January to December 2009. This table summarizes the number and genotypes of patients enrolled and questionnaires collectedSexMaleFemaleTotal (%)TOTAL455196 (100)SCD Patients403575 (78)Healthy Controls51621 (22)Hemoglobin Genotype of SCD patientsSS141529 (38.6)Sβ010919 (25.3)Sβ+112 (2.6)SC112 (2.6)SO101 (1.3)unknown13922 (29.3)Total (%)403575 (100)Questionnaires filled282654No questionnaires111021 Disclosures: No relevant conflicts of interest to declare.

scholarly journals Is there a role for selective vasodilation in the management of sickle cell disease?

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 597-602 ◽  
Author(s):  
GP Rodgers ◽  
MS Roy ◽  
CT Noguchi ◽  
AN Schechter
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Microvascular Obstruction ◽  
Controlled Study ◽  
Control Group ◽  
Cell Disease ◽  
Retinal Arteriolar

Abstract To test the hypothesis that microvascular obstruction to blood flow at the level of the arteriole may be significant in individuals with sickle cell anemia, the ophthalmologic effects of orally administered nifedipine were monitored in 11 steady-state patients. Three patients with evidence of acute peripheral retinal arteriolar occlusion displayed a prompt reperfusion of the involved segment. Two other patients showed fading of retroequatorial red retinal lesions. Color vision performance was improved in six of the nine patients tested. The majority of patients also demonstrated a significant decrease in the amount of blanching of the conjunctiva which reflects improved blood flow to this frequently involved area. Such improvements were not observable in a control group of untreated stable sickle cell subjects. These findings support the hypothesis that inappropriate vasoconstriction or frank vasospasm may be a significant factor in the pathogenesis of the microvascular lesions of sickle cell disease and, further, that selective microvascular entrapment inhibition may offer an additional strategy to the management of this disorder. We believe a larger, placebo-controlled study with nifedipine and similar agents is warranted.

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