Blood viscosity is an important determinant of local flow characteristics, which exhibits shear thinning behavior: it decreases exponentially with increasing shear rates. Both hematocrit and plasma ...viscosity influence blood viscosity. The shear thinning property of blood is mainly attributed to red blood cell (RBC) rheological properties. RBC aggregation occurs at low shear rates, and increases blood viscosity and depends on both cellular (RBC aggregability) and plasma factors. Blood flow in the microcirculation is highly dependent on the ability of RBC to deform, but RBC deformability also affects blood flow in the macrocirculation since a loss of deformability causes a rise in blood viscosity. Indeed, any changes in one or several of these parameters may affect blood viscosity differently. Poiseuille's Law predicts that any increase in blood viscosity should cause a rise in vascular resistance. However, blood viscosity, through its effects on wall shear stress, is a key modulator of nitric oxide (NO) production by the endothelial NO-synthase. Indeed, any increase in blood viscosity should promote vasodilation. This is the case in healthy individuals when vascular function is intact and able to adapt to blood rheological strains. However, in sickle cell disease (SCD) vascular function is impaired. In this context, any increase in blood viscosity can promote vaso-occlusive like events. We previously showed that sickle cell patients with high blood viscosity usually have more frequent vaso-occlusive crises than those with low blood viscosity. However, while the deformability of RBC decreases during acute vaso-occlusive events in SCD, patients with the highest RBC deformability at steady-state have a higher risk of developing frequent painful vaso-occlusive crises. This paradox seems to be due to the fact that in SCD RBC with the highest deformability are also the most adherent, which would trigger vaso-occlusion. While acute, intense exercise may increase blood viscosity in
Aims
To provide an understanding of medical care adherence factors as reported by caregivers, adolescent, and adult patients with sickle cell disease and to analyse those concerns to identify ...barriers and facilitators about medical care adherence. Three topics influenced medical care adherence: the disease itself, therapeutics, and the healthcare system. This study will focus on the first topic.
Design
Qualitative explorative study, using semi‐structured and life‐experience interviews and manual inductive content analysis.
Methods
From December 2016 – March 2017, one semi‐structured interview was conducted by a researcher with each of the 15 adolescent patients, 10 adult patients, and 19 caregivers in a French public hospital. Interviews were audio‐taped and transcribed before a content analysis. Perceptions were classified into barriers and facilitators of medical care adherence.
Results
This article presents disease perceptions of caregivers and patients (adolescents and adults): daily management and social representations. These perceptions differ among parents, adolescent patients, and adult patients. However, all report important disease‐related “limitations” in their lives. The objective for adults (parents and patients) is to “live with the disease” and to achieve this, they find coping resources. Two major resources expressed by adults emerged: social resources (support from friends, patients’ association, and social visibility) and disease knowledge (theoretical and derived from experience). This is not the case of adolescents for whom social normality was the main concern.
Conclusion
Care management adherence is partly based on coping with the disease. Given the lower number of facilitators expressed by adolescents, it is essential to propose interventions in this population. It will help them cope with the disease and, consequently, optimize care management adherence.
Impact
Showing differences among caregivers, adult, and adolescent patient perceptions, this study impact future care practices. It revealed needs of intervention for adolescents.
目的
了解医护人员、青少年和成年镰状细胞病患者所报告的医疗护理依从性因素,并对此类因素进行分析,以确定相关医疗护理的障碍和促进因素。
医疗护理依从性主要与三大主题相关:疾病本身、疗法和医疗系统。本研究将围绕第一个主题展开。
设计
定性探索性研究,采用半结构化和生活经验访谈和手动归纳分析法。
方法
研究人员在2016年12月至2017年3月间,对法国一家公立医院的15名青少年患者、10名成年患者和19名医护人员进行了一次半结构化访谈。该访谈内容在分析之录音和转录。此类人员的认知均可划分为医疗护理依从性的障碍和促进因素。
结果
本文主要介绍医护人员和患者(青少年和成人)对疾病的认知,即:日常管理和社会表征。父母、青少年患者和成年患者对此观念的看法各异。然而,所有人都对其生活中疾病相关问题的“局限性”进行报告。成人(父母和患者)的目标是“与疾病抗争到底”,为实现此目标,其找到对应资源。成人主要需要两大资源,分别是:社会资源(朋友、患者协会和社会知名人士的支持)和疾病知识(理论和经验)。然而,这并不是青少年的关注点,对他们而言,社会常态更为重要。
结论
护理管理依从性部分是以疾病对抗对基础。鉴于青少年所述促进者人数较少,有必要对此人群提出干预措施。此类措施的提出有助于其应对疾病,从而优化护理管理的依从性。
影响
本研究显示护理人员、成人和青少年患者的认知差异,对未来护理实践有一定影响。本研究同样揭示青少年的干预需求。
Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by chronic anemia, intravascular hemolysis, and the occurrence of vaso-occlusive crises due to the mechanical obstruction of ...the microcirculation by poorly deformable red blood cells (RBCs). RBC deformability is a key factor in the pathogenesis of SCD, and is affected by various factors. In this study, we investigated the effects of adenylyl cyclase (AC) signaling pathway modulation and different phosphodiesterase (PDE) modulatory molecules on the deformability and mechanical stress responses of RBC from SCD patients (HbSS genotype) by applying 5 Pa shear stress with an ektacytometer (LORRCA). We evaluated RBC deformability before and after the application of shear stress. AC stimulation with Forskolin had distinct effects on RBC deformability depending on the application of 5 Pa shear stress. RBC deformability was increased by Forskolin before shear stress application but decreased after 5 Pa shear stress. AC inhibition with SQ22536 and protein kinase A (PKA) inhibition with H89 increased RBC deformability before and after the shear stress application. Non-selective PDE inhibition with Pentoxifylline increased RBC deformability. However, modulation of the different PDE types had distinct effects on RBC deformability, with PDE1 inhibition by Vinpocetine increasing deformability while PDE4 inhibition by Rolipram decreased RBC deformability after the shear stress application. The effects of the drugs varied greatly between patients suggesting some could benefit from one drug while others not. Developing drugs targeting the AC signaling pathway could have clinical applications for SCD, but more researches with larger patient cohorts are needed to identify the differences in the responses of sickle RBCs.
Abnormal retention of mitochondria into mature red blood cells (RBCs) has been recently reported in sickle cell anemia (SCA) but their functionality and their role in the pathophysiology of SCA ...remain unknown. The presence of mitochondria within RBCs was determined by flow cytometry in 61 SCA patients and 10 healthy donors. Patients were classified according to the percentage of mature RBCs with mitochondria contained in the whole RBC population: low (0-4%), moderate (>4 and 8%). RBC rheological, hematological, RBC senescence and oxidative stress markers were compared between the three groups. RBC senescence and oxidative stress markers were also compared between mature RBC containing mitochondria and those without. The functionality of residual mitochondria in sickle RBCs was measured by high-resolution respirometry assay and showed detectable mitochondrial oxygen consumption in sickle mature RBCs but not in healthy RBCs. Increased levels of mitochondrial reactive oxygen species (ROS) were observed in mature sickle RBCs when incubated with Antimycin A vs without. In addition, mature RBCs retaining mitochondria exhibited greater levels of ROS compared to RBCs without mitochondria, as well as greater Ca2+, lower CD47 and greater phosphatidylserine exposure. Hematocrit and RBC deformability were lower, and the propensity of RBC to sickle under deoxygenation was higher, in the SCA group with a high percentage of mitochondria retention in mature RBCs. This study showed the presence of functional mitochondria in mature sickle RBCs, which could favor RBC sickling and accelerate RBC senescence, leading to increased cellular fragility and hemolysis.
Despite the fact that Red Blood Cells (RBCs) have been intensively studied in the past 50 years to characterize mechanical phenotypes associated with both healthy and pathological states, only ...ektacytometry (i.e., laser diffractometry) is currently used by hematologists to screen for RBC membrane disorders. Therefore, the development of new diagnostic tools able to perform analysis at the scale of a single cell, over a statistically relevant population, would provide important complementary information. But these new diagnostic tools would have to be able to discriminate between different disorders causing a change in RBCs mechanical properties. We evaluated the mechanical response of artificially rigidified RBCs flowing through a microfluidic constriction. The geometry consists in a 50 μm wide channel with a succession of 14 tooth-like patterns, each composed of a 5 μm wide and 10 μm long constriction, associated with a 25 μm wide and 10 μm long enlargement. RBCs deformability was altered using two chemical treatments, known to affect RBCs membrane surface area and membrane deformability, lysolecithine (LPC) and diamide, respectively. Differences between samples were highlighted by the representation of the inverse of the shape recovery time (1/τ r ), versus the extension at the exit of the constriction, D out . The results demonstrate that our approach is able to provide a direct signature of RBCs membrane composition and architecture, as it allows discriminating the effect of changes in RBCs membrane surface area from changes in RBCs membrane deformability. Finally, in order to evaluate the potential of our microsystem to detect pathological cells, we have performed preliminary experiments on patients with Hereditary Spherocytosis (HS) or Sickle Cell Anemia (SCA).
Patients with sickle cell disease (SCD) have poorly deformable red blood cells (RBC) that may impede blood flow into microcirculation. Very few studies have been able to directly visualize ...microcirculation in humans with SCD. Sublingual video microscopy was performed in eight healthy (HbAA genotype) and four sickle cell individuals (HbSS genotype). Their hematocrit, blood viscosity, red blood cell deformability, and aggregation were individually determined through blood sample collections. Their microcirculation morphology (vessel density and diameter) and microcirculation hemodynamics (local velocity, local viscosity, and local red blood cell deformability) were investigated. The De Backer score was higher (15.9 mm
) in HbSS individuals compared to HbAA individuals (11.1 mm
). RBC deformability, derived from their local hemodynamic condition, was lower in HbSS individuals compared to HbAA individuals for vessels < 20 μm. Despite the presence of more rigid RBCs in HbSS individuals, their lower hematocrit caused their viscosity to be lower in microcirculation compared to that of HbAA individuals. The shear stress for all the vessel diameters was not different between HbSS and HbAA individuals. The local velocity and shear rates tended to be higher in HbSS individuals than in HbAA individuals, notably so in the smallest vessels, which could limit RBC entrapment into microcirculation. Our study offered a novel approach to studying the pathophysiological mechanisms of SCD with new biological/physiological markers that could be useful for characterizing the disease activity.
Chronic hemolysis, enhanced oxidative stress, and decreased nitric oxide (NO) bioavailability promote vasculopathy in sickle cell anemia (SCA). Oxidative stress and NO are known to modulate eryptosis ...in healthy red blood cells (RBCs); however, their role in SCA eryptosis and their impact on the genesis of RBC-derived microparticles (RBC-MPs) remains poorly described. RBC-MPs could play a role in vascular dysfunction in SCA. The aims of this study were to evaluate the roles of oxidative stress and NO in eryptosis and RBC-MPs release, and to determine whether RBC-MPs could be involved in vascular dysfunction in SCA. Markers of eryptosis and oxidative stress, plasma RBC-MPs concentration and arterial stiffness were compared between SCA and healthy (AA) individuals
experiments were performed to test: 1) the effects of oxidative stress (antioxidant: n-acetylcysteine (NAC); pro-oxidant: cumene hydroperoxide) and NO (NO donor: sodium nitroprusside (SNP); NO-synthase inhibitor (L-NIO)) on eryptosis, RBC deformability and RBC-MP genesis; 2) the effects of SCA/AA-RBC-MPs on human aortic endothelial cell (HAEC) inflammatory phenotype and TLR4 pathway. Eryptosis, RBC-MPs, oxidative stress and arterial stiffness were increased in SCA. NAC increased RBC deformability and decreased eryptosis and RBC-MPs release, while cumene did the opposite. SNP increased RBC deformability and limited eryptosis, but had no effect on RBC-MPs. L-NIO did not affect these parameters. Arterial stiffness was correlated with RBC-MPs concentration in SCA. RBC-MPs isolated directly from SCA blood increased adhesion molecules expression and the production of cytokines by HAEC compared to those isolated from AA blood. TLR4 inhibition alleviated these effects. Our data show that oxidative stress could promote eryptosis and the release of RBC-MPs that are potentially involved in macrovascular dysfunction in SCA.
Blood rheology plays a key role in the pathophysiology of sickle cell anaemia (SS) and sickle cell haemoglobin C disease (SC), but its evolution over the lifespan is unknown.
Blood viscosity, red ...blood cell (RBC) deformability and aggregation, foetal haemoglobin (HbF) and haematocrit were measured in 114 healthy individuals (AA), 267 SS (161 children + 106 adults) and 138 SC (74 children + 64 adults) patients.
Our results showed that 1) RBC deformability is at its maximal value during the early years of life in SS and SC populations, mainly because HbF level is also at its peak, 2) during childhood and adulthood, hydroxycarbamide treatment, HbF level and gender modulated RBC deformability in SS patients, independently of age, 3) blood viscosity is higher in older SS and SC patients compared to younger ones and 4) haematocrit decreases as SS patients age.
The hemorheological changes detected in older patients could play a role in the progressive development of several chronic disorders in sickle cell disease, whose prevalence increases with age. Retarding these age-related haemorheological impairments, by using suitable drugs, may minimize the risks of vaso-occlusive events and chronic disorders.
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