scholarly journals LEVERAGING PLASMA-DERIVED EXOSOMES FOR BIOMARKER DISCOVERY IN SICKLE CELL DISEASE: PREPARATION FOR A LARGE PROSPECTIVE STUDY

2020 ◽  
Vol 42 ◽  
pp. 47
Author(s):  
Y. Lamarre ◽  
A. Aich ◽  
M. Islam ◽  
J.M. Scianni ◽  
A.C.S. Pinto ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Prospective Study ◽  
Sickle Cell ◽  
Biomarker Discovery ◽  
Cell Disease ◽  
Large Prospective Study

scholarly journals Neuropathic Pain in Children with Sickle Cell Disease: The Hidden Side of the Vaso-Occlusive Crisis

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 84
Author(s):  
Jeanne Sigalla ◽  
Nathalie Duparc Alegria ◽  
Enora Le Roux ◽  
Artemis Toumazi ◽  
Anne-Françoise Thiollier ◽  
...  
Keyword(s):  
Risk Factors ◽  
Neuropathic Pain ◽  
Sickle Cell Disease ◽  
Sex Ratio ◽  
Prospective Study ◽  
Sickle Cell ◽  
Clinical Presentation ◽  
Early Stage ◽  
Cell Disease ◽  
A Prospective Study

The majority of hospitalizations of patients with sickle cell disease (SCD) are related to painful vaso-occlusive crises (VOCs). Although the pain of VOC is classically nociceptive, neuropathic pain (NP) has also been demonstrated in SCD patients. The aim of our study is to specify the prevalence of NP during VOCs in SCD children using a dedicated scale and to measure its characteristics. We performed a prospective study that included SCD children hospitalized for an acute VOC. The presence of NP was sought with the DN4 scale on the second and fourth days of hospitalization. A total of 54 SCD children were included in the study. Overall, 41% of the patients (n = 22) experienced neuropathic pain during the VOC, mostly at an early stage (Day 2). The median age, the sex ratio, the location of the pain, and the morphine consumption were similar for patients with and without NP. Our study shows that neuropathic pain is very common during VOCs in SCD children. The absence of identified risk factors should prompt us to be vigilant regardless of the patient’s age, sex, and clinical presentation.

Incidence and Risk of Delayed Hemolytic Transfusion Reaction in Sickle Cell Disease Patients Based on a Prospective Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 95-95 ◽  
Author(s):  
France Pirenne ◽  
David Narbey ◽  
Philippe Chadebech ◽  
Armand Mekontso-Dessap ◽  
Pablo Bartolucci ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Prospective Study ◽  
Sickle Cell ◽  
Acute Chest Syndrome ◽  
Transfusion Reaction ◽  
Cell Disease ◽  
Hemolytic Transfusion Reaction ◽  
Delayed Hemolytic Transfusion Reaction ◽  
Prospective Longitudinal

Abstract Background Delayed hemolytic transfusion reaction (DHTR) is a life threatening complication of transfusion in sickle cell disease (SCD). This syndrome is underestimated because of a clinical picture that resembles a vaso-occlusive crisis (VOC) and the frequent absence of detectable antibodies. Several retrospective studies have evaluated the frequency of DHTR based on case reports. We conducted a prospective, longitudinal, single center study to determine the incidence of DHTR and the risk of developing DHTR depending on the transfusion regimen: chronic versus punctual. Methods and patients SCD patients aged over 18 years, undergoing a transfusion, were enrolled in this study. A total of 697 transfusion episodes (TE) in 312 patients were included during 30 months. Some patients had multiple TE during the period. The post transfusion outcome of the patients was assessed up to one month after the included TE. DHTR was confirmed based on the rapid disappearance of HbA (> 50% 15 days post-transfusion) associated with two of the following criteria up to three weeks after transfusion: VOC symptoms, dark urine, worsening anemia, increased LDH. Transfusion episodes were divided into chronic (336 TE in 111 patients) and punctual (361 TE in 201 patients). Chronic transfusions were defined as regular transfusions to treat chronic complications or for primary/secondary prevention of complications. Short transfusion program during pregnancy was considered as punctual transfusions if patients were not previously regularly transfused. The study obtained approval of the local Ethics Committee. Results Follow-up of the patients after transfusion showed 15 DHTR during the study. They all developed in punctually transfused patients. Thus, patients who are transfused punctually have a significantly higher risk of developing DHTR than those in a regular transfusion program (p < 0.001). When considering only punctual transfusions, the incidence of DHTR is 4.2% per transfusion episode (IC 95% [2.6; 6.9]) and 7.5% per patient during the 30 months of the study (IC 95% [4.6; 12.4]). In these DHTR cases, the transfusion indication was surgery (n = 6), pregnancy (n = 3), acute chest syndrome (n = 3), stroke (n = 1), profound anemia (n = 1), and VOC prevention before a school exam (n = 1 case). Two patients died of multi-organ failure following severe intravascular hemolysis. The median hemoglobin decrease for all DHTR cases after the triggering transfusion was 4.4 g/dl [IQR 3.6-5.2]; the highest LDH level was 879 [IQR 680-1423]. Ten patients developed newly formed antibodies, but only five among them displayed antibodies with significant serological features (anti-Fya, anti-S, anti-Jka, anti-HI). In the five other cases, the antibodies were of unspecified specificity or auto antibodies in the RH blood group (the genetic RH background was known). Finally, antibodies were undetectable for five cases, confirmed by long-term patient follow up. Conclusion This prospective study demonstrates, for the first time, that DHTR is a frequent reaction in adult SCD patients, developing only in occasionally transfused patients. This finding highlights that adult patients with regular transfusion who did not previously encountered DHTR are not susceptible to developing this severe reaction. A mechanism linked to acute situations can be suggested as already shown for the induction of allo-immunization. However, many cases developed without detectable antibodies, confirming the complex pathophysiology of this syndrome. A bio-clinical scoring system to predict DHTR, based on this study, is under development and will be presented. Disclosures Michel: Roche: Research Funding.

Proteomic-Based Approach for Biomarker Discovery to Predict Silent Cerebral Infarct in Patients with Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2579-2579
Author(s):  
Lisa M. Williams ◽  
Zongming Fu ◽  
Pratima Dulloor ◽  
William J Savage ◽  
Emily Barron-Casella ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Plasma Proteins ◽  
Biomarker Discovery ◽  
Neurofibrillary Tangle ◽  
Integrated Analysis ◽  
Cell Disease ◽  
Nucleosome Remodeling ◽  
Specific Proteins ◽  
Brain Specific Proteins

Abstract Abstract 2579 Poster Board II-556 Silent cerebral infarction (SCI) is part of a spectrum of cerebrovascular disease, occurs in approximately 22% of children with sickle cell disease (SCD) and is associated with decreased cognitive function. While several plasma biomarkers have been shown to be elevated in acute stroke, to our knowledge none have been evaluated in SCD or SCI. The aim of this study was to develop a reliable pipeline to identify low abundance plasma proteins that correlate with SCI in patients with SCD. We used a proteomic discovery approach involving three sequential separation steps in order to compare the plasma proteomes in a discovery set of 15 children with SCD (7 children with SCI and 8 children without SCI). Baseline steady state plasma samples obtained from the Silent Infarct Transfusion (SIT) Trial Biologic Repository were matched for age and WBC. In the first dimension, hemoglobin was depleted with nickel-nitrilotriacetic acid (Ni-NTA). Subsequently, second dimension separation and enrichment was achieved by immunoaffinity depletion of the 12 most abundant proteins (ProteomeLab IgY-12 LC10) followed by third dimension separation by reverse phase liquid chromatography fractionation (RPLC) using a C18 column and a linear acetonitrile gradient. Collected fractions were subjected to tryptic digestion and analyzed using label-free quantification on a LTQ-Orbitrap (Thermo) mass spectrometer. The MS/MS data were analyzed using the Proteomics Analyzer Software System (PASS) version 4.0.10 (Integrated Analysis Inc, Bethesda, MD) with X! Tandem searches (www.thegpm.org; version 2008.12.01) using the human IPI database. Identified proteins were compared to databases of brain specific and brain enriched proteins to identify candidate biomarker proteins for SCI. After hemoglobin depletion, 71% of total protein was removed. On average, protein recovery after the LC-12 column was 4% of the total Ni-NTA depleted protein. Of the 9800 proteins that were identified in the plasma proteome of children with SCD, 23 were brain specific proteins. Evaluation of the relative abundance by spectral counts (SC) revealed 3 brain-related proteins that were over-represented in patients with SCI: microtubule-associated protein tau (a neurofibrillary tangle protein implicated in Alzheimer disease, frontotemporal dementia and parkinsonism), neuroligin-3 (a neuronal cell surface protein proposed to be involved in cell-cell-interactions via binding to beta-neurexins and implicated in autism and Asperger syndrome), and nucleosome-remodeling factor subunit BPTF (a histone-binding component of nucleosome-remodeling factor that is abundantly expressed in the fetal brain and re-expressed in neurodegenerative diseases). Reticulon-4, a potent neurite growth inhibitor involved in the restriction of axonal regeneration after injury, was under-represented in patients with SCI. After depletion of hemoglobin and other high abundant proteins, we were able to develop a database of plasma proteins in children with SCD and to identify brain specific proteins as potential surrogate markers of brain injury. These markers may be implicated in the pathophysiology of SCI. Although validation studies are necessary to determine the relevance of these candidate biomarkers in SCI and SCD, our methodology appears to be a practical approach to proteomic discovery in patients with hemolytic anemia. Disclosures: Casella: Boehringer Ingelheim: Honoraria, Research Funding, Travel funding.

scholarly journals Clinical and haematological risk factors for cerebral macrovasculopathy in a sickle cell disease newborn cohort: a prospective study

2016 ◽  
Vol 172 (6) ◽  
pp. 966-977 ◽  
Author(s):  
Julie Sommet ◽  
Corinne Alberti ◽  
Nathalie Couque ◽  
Suzanne Verlhac ◽  
Zinedine Haouari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Prospective Study ◽  
Sickle Cell ◽  
Cell Disease ◽  
A Prospective Study

scholarly journals A prospective study of the association between sickle cell disease and hepatobiliary effects in Bahrain

2017 ◽  
Vol Volume 10 ◽  
pp. 221-226
Author(s):  
Maheeba A Abdulla ◽  
Fajer Juma Almoosa ◽  
Rana Juma Al Moosa ◽  
Jehad Al Qamish
Keyword(s):  
Sickle Cell Disease ◽  
Prospective Study ◽  
Sickle Cell ◽  
Cell Disease ◽  
A Prospective Study

scholarly journals Tolerance and humoral immune response to the yellow fever vaccine in sickle cell disease children treated with hydroxyurea: a multicentre prospective study

2021 ◽  
Author(s):  
Berengere Koehl ◽  
Camille Aupiais ◽  
Nelly Schinckel ◽  
Pierre Mornand ◽  
Marie-Hélène Odièvre ◽  
...  
Keyword(s):  
Immune Response ◽  
Sickle Cell Disease ◽  
Adverse Events ◽  
Prospective Study ◽  
Antibody Titre ◽  
Yellow Fever ◽  
Sickle Cell ◽  
Cell Disease ◽  
Protective Antibody ◽  
Antibody Titres

Abstract Background Sickle cell disease (SCD) children are frequent travellers to countries where yellow fever (YF) is endemic, but there are no data regarding the safety and immunogenicity of the vaccine in such children treated with hydroxyurea (HU). The main objective of this study was to compare the tolerance and immune response to YF vaccination in SCD children treated or not with HU. Method SCD children &lt; 18 years attending the international travel clinics of three large paediatric centres and requiring a first YF vaccination were included in a prospective study. Adverse events were collected 2 weeks after vaccination. YF vaccine antibody titres were measured ~6 months after vaccination. Results Among the 52 SCD children vaccinated against YF, 17 (33%) were treated with HU. Only mild adverse events, mainly fever and local reaction, were observed in the HU group with a similar frequency in the non-HU group (57 and 35%, respectively, P = 0.30). YF antibody titres were measured in 15/17 patients in the HU group and 23/35 patients in the non-HU group after a median of 6.0 months (3.5–8.5) following vaccination. The geometric mean of YF antibody titre was similar in both groups. A protective antibody level was observed in 85% of the children in the HU group vs 100% in the non-HU group (P = 0.14), suggesting a lower effectiveness of the vaccine in patients on HU similarly to what has been described in patients on immune suppressive therapy for other vaccines. Conclusion YF vaccination seems to be safe and efficient in SCD children treated with HU. Considering the potential risk of severe complications in cases of YF while travelling in Africa for those patients, the benefit-to-risk ratio argues for YF vaccination in all SCD children. Control of a protective antibody titre may also be useful to ascertain an adequate response in those treated with HU.

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