化学修饰血红蛋白替代红细胞载氧的研究

用血代用品替代传统的输血一直是人们努力的方向。化学修饰血红蛋白是红细胞代用品 的热点之一，对血红蛋白化学修饰的目的是适当降低血红蛋白同氧的亲和力，将血红蛋白大分子化，提高纯化后的终产品得率。本文就化学修饰血红蛋白替代红细胞载氧的有关研究情况做了综述。     

红细胞代用品的研制及趋势

输血作为重要的创伤救治手段却因血液的保存及输血过程中的诸多不便而在应用上受到限制，为此，旨在部分地替代红细胞载氧功能的红细胞代用品的研制便具有了十分重要的意义。本简述了红细胞代用品研制的历史及现状，重点介绍了目前正在研制的基于血红蛋白的第三代红细胞代用品的制备及载氧性能研究状况和趋势。     

红细胞代用品的研制及趋势

输血作为重要的创伤救治手段却因血液的保存及输血过程中的诸多不便而在应用上受到限制，为此，旨在部分地替代红细胞载氧功能的红细胞代用品的研制便具有了十分重要的意义。本文简述了红细胞代用品研制的历史及现状，重点介绍了目前正在研制的基于血红蛋白的第三代红细胞代用品的制备及载氧性能研究状况和趋势。     

红细胞代用品的研究进展

输血来源有限，且输注后可能引起严重的不良反应，因而国内外科学家对以携氧液作为输血替代品进行了长达一个多世纪的探索。迄今为止，几种第一代红细胞代用品已经有望获准上市。各种产品有其独自的生理特性、生物活性和副作用。作者着重综述了基于人，牛和重组来源血红蛋白衍生的红细胞代用品以及携氧氟碳乳剂，描述了多聚血红蛋白（PolyHeme，HBOC-201，Hemolink），双阿司匹林分子内交联血红蛋白（HemAssist），重组人血红蛋白（rHb1．1，rHb2．0），共轭血红蛋白（PHP，MP4），血红蛋白微囊，全合成型白蛋白-血红素载体和氟碳乳剂（Oxygent，Oxyiluor，Perftoran）等红细胞代用品的研制情况，产品特性，生理学效应，实（试）验效能和副作用。作为氧治疗剂进行研发，可能成为今后红细胞代用品研制的发展方向。     

血液组织工程制品的研究现状

广义上血液代用品包括血浆代用品和血细胞代用品,狭义上主要指红细胞代用品、血小板代用品和白细胞代用品.红细胞代用品主要包括全氟碳化合物类、血红蛋白类(Hb)和微囊化血红蛋白类.目前全世界范围内广泛研究的血红蛋白类红细胞代用品有:以人Hb为基础、以动物Hb为基础及以基因重组人Hb为基础的红细胞代用品.白细胞的功能和免疫问题十分复杂,临床单独输用甚少.目前研究开发的血小板代用品主要是脂质体类和胶原纤维类.     

改性血红蛋白人工血进展

取自天然红细胞的血红蛋白(Hb)经化学改性制成血液代用品(人工血),具有应用时不受患者血型限制并可避免病毒传播的特点,在物理性能和携氧能力方面优于氟碳化物。本文介绍了改性血红蛋白人工血进展情况,包括微包囊Hb、化学改性Hb制品;Hb生物相容性及毒性反应机理;Hb在治疗中的应用。文章认为,Hb制品资源问题已解决,就纯度、性能、疗效及价格而论,用牛Hb甚至优于人血Hb,改性Hb作为血液代用品具有广阔前景。     

血红蛋白溶液的研究进展

血红蛋白溶液是近年来研究较多且较有前途的载氧血液代用品,目前主要有修饰血红蛋白和微囊化血红蛋白等,前者是通过化学方法将血红蛋白进行分子间和/或分子内交联,后者则是用人工膜将血红蛋白分子进行包裹。最终目的是降低血红蛋白的氧亲和力,提高向组织释氧能力,同时延长血红蛋白在循环中的半衰期。血红蛋白的来源主要有过期库血及动物(主要是牛)血,随着分子生物学的发展,目前对基因工程血红蛋白的研究正逐步深入。虽然现在已有数种产品进入临床前或I期临床试验阶段,但仍有一定的副作用,尚需进一步研究。     

聚合物微囊型血液代用品携氧-释氧性能的无损检测方法

P50是衡量血液代用品携氧一释氧性能的重要指标。本研究借鉴临床脉冲血氧饱和度仪的工作原理，利用近红外光具有强穿透性（能穿透可生物降解聚合物壳材并对包封在壳材内的血红蛋白进行检测），结合氧合血红蛋白和脱氧血红蛋白在近红外光区域有不同的吸收光谱特性，采用自行研制的密封、平衡装置完成对载牛血红蛋白微囊型血液代用品的血氧饱和度和对应氧分压的测定，从而得出氧解离曲线、P50等携氧．释氧指标。该套装置和方法无需破损微囊，过程简单，可实现对聚合物微囊型血液代用品携氧一释氧性能的无损、在位检测。     

肾上腺素对红细胞血红蛋白携氧能力的影响

目的:探讨肾上腺素是否影响红细胞血红蛋白的携氧能力。方法:应用拉曼光谱扫描光谱分析肾上腺素作用下及酸性环境下的红细胞氧合血红蛋白的改变。采集健康人红细胞,悬浮于不同pH值(pH 5.0、pH7.4)等渗PBS缓冲液,肾上腺素预处理红细胞,在拉曼光谱点扫描分析检测单个活态红细胞内血红蛋白特征光谱变化。结果:酸性环境下,红细胞的氧合血红蛋白特征峰在肾上腺素的作用下显著升高(P0.05);而在正常pH时,肾上腺素的这一作用不明显(P0.05)。结论:肾上腺素在酸性环境时增加红细胞血红蛋白的氧合力,减少氧从血红蛋白的解离,不利于缺氧组织供氧。     

人脐带血血红蛋白的分离纯化与病毒灭活研究

建立了一套通过热敏法分离纯化及病毒灭活人脐带血血红蛋白的工艺。对该工艺条件的优化。使得纯化血红蛋白产品纯度及回收率等得到提升，并建立了一套较为完善的纯化血红蛋白质量检测指标。与现有的纯化方式相比。热敏法操作简便。仪器设备造价低廉。纯化与病毒灭活同时进行，得到的纯化产品损失少，纯度高。各项理化指标达到国际水平。为规模制备纯化及病毒灭活的血红蛋白以及血液代用品的研发创造了有利条件。     

Artificial blood

Artificial blood is a product made to act as a substitute for red blood cells. While true blood serves many different functions, artificial blood is designed for the sole purpose of transporting oxygen and carbon dioxide throughout the body. Depending on the type of artificial blood, it can be produced in different ways using synthetic production, chemical isolation, or recombinant biochemical technology. Development of the first blood substitutes dates back to the early 1600s, and the search for the ideal blood substitute continues. Various manufacturers have products in clinical trials; however, no truly safe and effective artificial blood product is currently marketed. It is anticipated that when an artificial blood product is available, it will have annual sales of over $7.6 billion in the United States alone.     

Theoretical determination of the blood's relative oxygen saturationin vivo

The diffusion equations for randomly directed photons are applied to the problem of thein vivo determination of the oxygen relative saturation in blood. A model of the living tissue is presented. The transmitted and backscattered light fluxes are calculated for various skin properties, volume occupied by the blood and the blood relative oxygen saturation. Normalization functions are introduced and analyzed for sensitivities to changes in several parameters. The photodiffusion theoretical treatment is suggested for calculations which will lead to optimal normalization techniques and transducer design for thein vivo measurements of the oxygen relative saturation in the blood.     

Quality management of blood collection

The objective of the quality management in the blood transfusion service is the continuous improvement of the quality of the processes and the products related to the blood donation of the blood donors, the production of the blood components and the transfusion of the blood products to the recipients. The efficacy, the safety and the efficiency of the blood transfusion processes requires that the personnel is educated and trained, that processes are described in standard operating procedures and that these procedures are followed up. When the concept of quality and the improvement of quality is in the mind of all working in the field of blood transfusion medicine, the quality of the blood transfusion service will go upwards, the donors will feel themselves respectfully treated and rewarded, the blood products will become more efficacious and safe, and the patients will receive the best products available. Quality management of blood collection implies the processes on donor recruitment, donor handling and donor vigilance, and the process of donation and screening. For all processes in blood collection, quality indicators should be defined and these data should be monitored, collated, analysed, reported and used in order to improve the quality of the processes.     

Is there a causal relationship between the receipt of blood transfusions and the development of chronic lung disease of prematurity?

The number and total volume of blood transfusions received by premature babies is, after gestational age and birth weight a good predictor of the likelihood of developing chronic lung disease of prematurity (CLD) and retinopathy of prematurity (ROP). Oxidative damage, inflammation and pulmonary infections are also strongly associated with the development of CLD. It is currently not clear whether there is a causal relationship between the receipt of blood transfusions and oxidative damage, infection, inflammation and CLD in these babies. Strong arguments may be made both for and against a causal relationship. The babies who receive blood transfusions are usually smaller than those who do not, and are ventilated, often with high oxygen levels, for a longer period of time. The longer the baby is on a ventilator the more likely it is to develop pulmonary infection and inflammation. All these factors will promote free radical production and oxidative damage irrespective of the receipt of blood transfusion. This would argue against a causal relationship. On the other hand, an argument may be presented which is based on iron promoted free radical generation, infection and fibrosis consequent to the breakdown of haeme released from transfused erythrocytes. Haeme is broken down by haeme oxygenase (HO) to iron, CO and bilirubin. Under normal circumstances the products of HO activity are beneficial to the organism, but when HO activity is excessive, the products are potentially damaging. Free iron, (in the Fe2+ form) if not sequestered with protein or urate, will generate highly toxic free radicals via the Fenton and Heber-Wiess reactions, predispose the tissue to infection and promote fibrosis. The iron chelating ability of the premature baby appears to be limited so that it would be difficult to deal with any increase in free iron production. Free iron will in turn induce HO activity leading to a potentially serious positive feedback process. The lung is particularly sensitive to iron induced HO activity. In addition, HO activity may be enhanced by other events occurring in the premature lung such as the production of proinflammatory cytokines and the reduced level of glutathione. Thus, the possibility of a causal relationship clearly exists and needs to be examined. This can be attempted by measuring the products of HO activity in relation to the receipt of blood transfusions.     

Disease transmission by blood products: past,present and future

Transfusion of blood and blood products has been associated with transmission of infectious agents. However, it is probable that blood products are currently very safe and that pooled virus-inactivated products from remunerated donors are now safer than untreated single voluntary donor components. Although the transmission events of the past and the present are reasonably well understood, reliance on a linear approach to predict safety in the future is open to criticism. Indeed, it was not possible to predict the extent or consequences of the AIDS epidemic or of hepatitis C transmission. Moreover, although variant Creutzfeldt-Jakob disease (vCJD) may not be transmitted to any large extent by transfusion of manufactured blood products, this will be due more to good fortune than good judgement - this agent could have escaped the screening, testing and eradication methods on which current confidence in blood product safety depends. Similarly, the emergence of a highly resistant non-enveloped virus, or even of another previously unrecognised disease-causing agent, could result in new threats from transfusion of blood components and products. The ecology of blood transfusion is exquisitely sensitive to variations in starting conditions, a situation typical of a chaotic rather than a linear system. Seemingly trivial events, often apparently unrelated to blood transfusion, have had enormous consequences in this field. Whatever the events that introduced simian immunodeficiency virus to humans or scrapie to cattle, they were a long way from those involved in the manufacture of blood products. In such a setting, reliance on methods that deal effectively with known threats (such as encapsulated viruses and bacteria) without adequate investigation and management of the intrinsic sensitivity to unpredictable events, leaves open the possibility of further infections emerging in the future. It is this reality that will ultimately result in the eradication of the transfusion of donor-derived blood and blood products in the developed world. In addition, all infections with a long disease-free incubation period in the host that can be transmitted in blood will eventually be over-expressed in groups that are exposed to blood either recreationally or professionally. As in the past, this could have occurred before testing or decontamination processes have been developed for emerging pathogens. Failure to be able to rely on completely risk-free donors, in both the voluntary and non-voluntary sides of the blood industry, continues to offer the potential for the transmission of infectious diseases in the future.     

Detection of bacterial growth in blood components using oxygen consumption as a surrogate marker in a tertiary oncology setup

Microbiological contamination of blood and blood products is a well-recognised transfusion risk. This study was performed in the blood bank of our oncology centre, with an objective to detect bacterial contamination in our blood products using oxygen consumption as a surrogate marker [Pall Enhanced Bacterial Detection System (eBDS)]. Results revealed that the percentages of failed units were 1.16% for random donor platelets (RDP), 0.81% for single donor platelets (SDP) and 2.94% for packed red blood cells (PRBCs), of which one RDP and one SDP grew coagulase-negative staphylococcus, while one PRBC culture grew Gram-positive bacilli.     

Prospects in blood transfusion]

What will be the evolution of blood transfusion in the next 10 years? What are the scientific and medical arguments to help the decision makers to propose the developments? Many scientific and clinical studies show that blood substitutes are not ready for use in man. So, for a long time, blood collection in man will still be a necessity to prepare cell concentrates (red blood cells and platelets) and fresh frozen plasma. During this period, blood safety will be based on development of testing technics and preparation processes of blood products. Another major point will be a better clinical use of blood derivates. Cellular therapy will be probably only a way of diversification in blood transfusion centers in partnership with hospitals.     

The prospective of the biotechnology industry on changing technology in pathology

Recent rapid developments in biotechnology are causing both an evolution and a revolution in science, medicine, and society. A number of potentially useful therapeutic products, diagnostics, blood products, and vaccines have been and will be developed that will represent great advances to the practicing physician and laboratory diagnostician. A large new industry is resulting and with this new science, new social and ethical issues are being raised, such as in regard to gene therapy, and will be debated for some years to come. As knowledge of the human genome increases, and further insights into the structure of receptors and the cell are obtained, even more useful products and technologies will emerge and change our lives over the next 20 years.     

Évolution de la distribution des produits sanguins labiles en France – analyse détaillée au sein d’un Établissement français du sang interrégional

ObjectiveThe present increase of blood products distribution raises some adaptation questions. To understand this evolution, it is necessary to assure patients needs satisfaction.Study designThe study focuses on years 1997 to 2007. All blood products and hospitals are taken into account. The possible impact of size and clinical specialties is analyzed for the main hospitals.ResultsThe evolution varies according to blood product: continuous drop for autologous red cells and plasmas, drop and rise for homologous red cells and platelets with a turnaround in 2001–2002, reverse and more chaotic movement for homologous plasmas. These movements are the result of public hospitals, with an upsurge of the medium sized ones. Private hospitals go down for all blood products, with a concentration on the larger ones. Surgical hospitals fall from 3 to 4% for all blood products, while medical ones rise of 3% for homologous red cells, 27% for platelets and fall of 10% for homologous plasmas. Private mixed hospitals fall for all blood products, while public ones rise for homologous red cells and platelets.ConclusionEvolution understanding of blood products distribution requires precisions about the kind of products and the hospitals status and specialties: medical, surgical, even obstetrical or urgency-related. The present trend is a rise for public hospitals and medical specialties, which are both the largest. Blood transfusion needs will thus go on rising in the years to come.     

Inactivation des pathogènes des produits sanguins labiles : entre enjeux financiers et conséquences possibles à long terme

Pathogen inactivation of blood products represents a global and major paradigm shift in transfusion medicine. In the next near future, it is likely that most blood products will be inactivated by various physicochemical approaches. The concept of blood safety will be challenged as well as transfusion medicine practice, notably for donor selection or biological qualification. In this context, it seems mandatory to develop analytical economic approaches by assessing costs-benefits ratio of blood transfusion as well as to set up cohorts of patients based on hemovigilance networks allowing rigorous scientific analysis of the benefits and the risks of blood transfusion at short- and long-term.