Dataset Information

Rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients.

ABSTRACT: In sickle cell disease (SCD), sickle hemoglobin (HbS) polymerizes upon deoxygenation, resulting in sickling of red blood cells (RBCs). These sickled RBCs have strongly reduced deformability, leading to vaso-occlusive crises and chronic hemolytic anemia. To date, there are no reliable laboratory parameters or assays capable of predicting disease severity or monitoring treatment effects. We here report on the oxygenscan, a newly developed method to measure RBC deformability (expressed as Elongation Index - EI) as a function of pO₂ . Upon a standardized, 22 minute, automated cycle of deoxygenation (pO₂ median 16 mmHg ± 0.17) and reoxygenation, a number of clinically relevant parameters are produced in a highly reproducible manner (coefficients of variation <5%). In particular, physiological modulators of oxygen affinity, such as, pH and 2,3-diphosphoglycerate showed a significant correlation (respectively R = -0.993 and R = 0.980) with Point of Sickling (PoS_5% ), which is defined as the pO₂ where a 5% decrease in EI is observed during deoxygenation. Furthermore, in vitro treatment with antisickling agents, including GBT440, which alter the oxygen affinity of hemoglobin, caused a reproducible left-shift of the PoS, indicating improved deformability at lower oxygen tensions. When RBCs from 21 SCD patients were analyzed, we observed a significantly higher PoS in untreated homozygous SCD patients compared to treated patients and other genotypes. We conclude that the oxygenscan is a state-of-the-art technique that allows for rapid analysis of sickling behavior in SCD patients. The method is promising for personalized treatment, development of new treatment strategies and could have potential in prediction of complications.

SUBMITTER: Rab MAE

PROVIDER: S-EPMC6518936 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients.

Rab Minke A E MAE van Oirschot Brigitte A BA Bos Jennifer J Merkx Tesy H TH van Wesel Annet C W ACW Abdulmalik Osheiza O Safo Martin K MK Versluijs Birgitta A BA Houwing Maite E ME Cnossen Marjon H MH Riedl Jurgen J Schutgens Roger E G REG Pasterkamp Gerard G Bartels Marije M van Beers Eduard J EJ van Wijk Richard R

American journal of hematology 20190308 5

In sickle cell disease (SCD), sickle hemoglobin (HbS) polymerizes upon deoxygenation, resulting in sickling of red blood cells (RBCs). These sickled RBCs have strongly reduced deformability, leading to vaso-occlusive crises and chronic hemolytic anemia. To date, there are no reliable laboratory parameters or assays capable of predicting disease severity or monitoring treatment effects. We here report on the oxygenscan, a newly developed method to measure RBC deformability (expressed as Elongatio ...[more]

PMID: 30784099

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Project description:The majority of morbidity and mortality in sickle cell disease is caused by vaso-occlusion: circulatory obstruction leading to tissue ischemia and infarction. The consequences of vaso-occlusion are seen clinically throughout the vascular tree, from the relatively high-oxygen and high-velocity cerebral arteries to the relatively low-oxygen and low-velocity postcapillary venules. Prevailing models of vaso-occlusion propose mechanisms that are relevant only to regions of low oxygen and low velocity, leaving a wide gap in our understanding of the most important pathologic process in sickle cell disease. Progress toward understanding vaso-occlusion is further challenged by the complexity of the multiple processes thought to be involved, including, but not limited to 1) deoxygenation-dependent hemoglobin polymerization leading to impaired rheology, 2) endothelial and leukocyte activation, and 3) altered cellular adhesion. Here, we chose to focus exclusively on deoxygenation-dependent rheologic processes in an effort to quantify their contribution independent of the other processes that are likely involved in vivo. We take advantage of an experimental system that, to our knowledge, uniquely enables the study of pressure-driven blood flow in physiologic-sized tubes at physiologic hematocrit under controlled oxygenation conditions, while excluding the effects of endothelium, leukocyte activation, adhesion, inflammation, and coagulation. We find that deoxygenation-dependent rheologic processes are sufficient to increase apparent viscosity significantly, slowing blood flow velocity at arterial oxygen tension even without additional contributions from inflammation, adhesion, and endothelial and leukocyte activation. We quantify the changes in apparent viscosity and define a set of functional regimes of sickle cell blood flow personalized for each patient that may be important in further dissecting mechanisms of in vivo vaso-occlusion as well as in assessing risk of patient complications, response to transfusion, and the optimization of experimental therapies in development.

Project description:Aims and objectivesTo assess the impact of educational interventions on the knowledge and attitude of healthcare professionals (HCPs) regarding sickle cell disease (SCD) pain management in the UK.BackgroundVariations and inadequate pain management due toHCPs' lack of knowledge and negative attitude is still an ongoing global concern for SCD patients despite availability of effective treatment and evidence-based guidelines. Several international studies have implemented interventions aimed at improving knowledge, attitude, and pain management. No review on the effectiveness of these interventions was found. Also, no previous intervention done in the UK was found from the thorough search of research databases. However, there are estimated 240,000 genetic carriers with about 12,500-15,000 estimated people living with SCD in the UK.DesignRapid Evidence Assessment of existing evidence.MethodsA rapid evidence assessment was conducted between March 2021-January 2022 following the PRISMA 2020 guidelines. Included papers must have an educational intervention about SCD or related symptom management where the learners were HCPs. Excluded papers were those not published in English or before 2010. The following databases were searched: CINAHL, MEDLINE, PubMed America and Europe, Scopus, PsycINFO and Web of Science. Data quality was assessed using the Mixed Methods Assessment Tool (MMAT) and analysed using a narrative approach.ResultsTen studies were included in the final review. Overall, they reported improved outcomes in six main themes: knowledge, attitude, perception, adoption, satisfaction and efficiency. Five studies reported statistically significant improvement in at least one outcome, four studies reported positive improvement, and two studies reported no significant improvement in knowledge and attitude. These heterogeneous studies were implemented once, and all designs were prone to bias; this makes it difficult to state how effective interventions are for SCD.ConclusionCurrent evidence of positive improvement in HCPs' knowledge and attitude is insufficient for generalisation and recommendation for adoption. However, we believe that implementing validated educational interventions remains essential for effective acute SCD pain management and patient-centred care. Further research is needed to find a suitable educational intervention that can be replicated.Relevance to clinical practiceQuality SCD education, timely crisis management and reduced patient stigma are crucial in reducing the risk of rapid clinical decompensation to avoid developing life-threatening complications. Understanding SCD can also support the building of therapeutic relationships between the patient and practitioner.Trial registrationThis review was not registered.

Dataset Information

Rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients.

Publications

Rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients.

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