Red blood cell function and blood storage

Red blood cells are ideal vehicles for delivering oxygen to tissues, but their functions deteriorate during liquid preservation. In this article, we review the role of red blood cells in oxygen delivery and methods to evaluate the effectiveness of red blood cell transfusion. Quantitative estimation of transfusion effects could avoid unnecessary transfusion and reduce the risk of transfusion-associated disorders. We also describe the benefits of transfusion of red blood cells having a higher oxygen-delivering capacity. Phosphoenolpyruvate is a promising component to prepare red blood cells having a higher oxygen-delivering capacity.     

Age and blood cell rheology

The identification of the rheological variables responsible for alterations in capillary blood flow caused by the aging process could help explain why the incidence of vascular disease increases with age. Using new techniques for the separation and micropore filtration of the haemocellular subpopulations in 110 subjects aged 21-84 years, the aim of this study was to show to what extent, if any, age influences blood cell deformability. The filterability of mononuclear leucocytes decreased with age (r = 0.25; p less than 0.001), whereas the filterability of polymorphonuclear leucocytes or erythrocytes did not change significantly with age.     

SE-9000血液分析仪有核红细胞提示分析

目的:分析sysmex SE-9000血液分析仪有核红细胞(NRBC)提示的可信性.方法:收集仪器白细胞栏有NRBC提示的标本100份,无NRBC提示的标本300份,涂片镜检,并与仪器结果进行比较.结果:32份单项NRBC提示的标本,镜检只4份有NRBC,其阳性符合率为12.5%;68份有NRBC同时有未成熟粒细胞(Imm Gran)、原始细胞(Blasts)、异型/异常淋巴细胞(Aty/Abn Ly)、核左移(Left)中一项或多项异常提示的标本,镜检48份有NRBC,阳性符合率为70.5%; 226份无NRBC及其它异常提示的标本,镜检1份有NRBC,假阴性率为0.4%;74份无NRBC但有Imm Gran、Blasts、Aty/Abn Ly、Left中一项或多项异常提示的标本,镜检4份有NRBC,假阴性率5.4%.结论:SE-9000血液分析仪对单项NRBC提示的假阳性率高,对有NRBC提示并同时有白细胞异常提示的阳性符合率较好,可信度较高,假阴性率低,对NRBC的检查起到过筛作用,明确镜检对象,缩小镜检范围.     

White blood cell counts and malaria

White blood cells (WBCs) were counted in 4697 individuals who presented to outpatient malaria clinics in Maesod, Tak Province, Thailand, and Iquitos, Peru, between 28 May and 28 August 1998 and between 17 May and 9 July 1999. At each site and in each year, WBC counts in the Plasmodium falciparum-infected patients were lower than those in the Plasmodium vivax-infected patients, which, in turn, were lower than those in the uninfected patients. In Thailand, one-sixth of the P. falciparum-infected patients had WBC counts of <4000 cells/microL. Leukopenia may confound population studies that estimate parasite densities on the basis of an assumed WBC count of 8000 cells/microL. For instance, in the present study, use of this conventional approach would have overestimated average asexual parasite densities in the P. falciparum-infected patients in Thailand by nearly one-third.     

Zebrafish myelopoiesis and blood cell development

The zebrafish (Danio rerio) animal model offers a unique opportunity to discover novel genes required for the control of normal vertebrate myeloid cell development. It is well suited for both developmental and genetic analyses: eg, genome-wide chemical mutagenesis screens have led to the identification of specific new genes affecting vertebrate erythropoiesis. Mutants defective in one or more hematopoietic functions will be useful as models of human disease and will assist in the elucidation of lineage-specific developmental programs. By using a combination of forward genetic mutagenesis screens and emerging strategies based on transgenic and antisense knockdown approaches, it should be possible to dissect the genetic programs that lead to myeloproliferative/myelodysplastic syndromes and to acute myeloid leukemia.     

Red blood cell blood group antigens: structure and function

Red blood cell (RBC) blood group antigens are polymorphic, inherited, carbohydrate or protein structures located on the extracellular surface of the RBC membrane. They contribute to the architecture of the RBC membrane, and their individual function(s) are being slowly revealed. The biological qualities assigned to these RBC membrane structures are based on observed physiological alteration in RBCs that lack the component, by documenting similarities in its protein sequence (predicted from the nucleotide sequence of the gene) to proteins of known function and by extrapolation to identified functional homologues in other cells. The varied roles of RBC antigens include membrane structural integrity, the transport of molecules through the membrane, as receptors for extracellular ligands, adhesion molecules, enzymes, complement components and regulators, and in glycocalyx formation.     

Red blood cell substitutes

Soluble polymerized haemoglobin (polyhaemoglobin) is now in a phase III clinical trials. Patients have received up to 20 units (10 litres) in trauma surgery and other surgery. Polyhaemoglobin can be stored for more than 1 year. Haemoglobin solutions have no blood group antigen and can be used as a 'universal donor' oxygen carrier. They can also be sterilized. With a circulation half-life of 24 hours they are undergoing trials for peri-operative use. For conditions with potential for ischaemia-reperfusion injuries, a new polyhaemoglobin-superoxide dismutase-catalase, which can reduce oxygen radicals, is being developed. Recombinant human haemoglobin has been tested in clinical trials, and a new type of recombinant human haemoglobin that has low affinity for nitric oxide is being developed for clinical trials. To increase the circulation time, artificial red blood cells have been prepared with a bilayer lipid membrane (haemoglobin liposomes) or with a biodegradable polymer membrane-like polylactide (haemoglobin nanocapsules). Synthetic chemicals such as perfluorochemicals are also being developed and tested in clinical trials as red blood cell substitutes.     

Restoration of red blood cell volume following 2-unit red blood cell apheresis

BACKGROUND AND OBJECTIVES: Blood donors who weigh at least 130 lbs (59 kg) and have a haematocrit of at least 40 V per cent can donate 2 units of blood, from which a 360-ml volume of red blood cells (RBC) can be isolated. This study was carried out in seven healthy male blood donors to assess the restoration of the RBC volume 1 month following a 2-unit RBC apheresis procedure. MATERIALS AND METHODS: RBC volumes were measured prior to donation and 4 weeks after the 2-unit RBC apheresis procedure without oral iron supplementation. RESULTS: Four weeks after the removal of 2 units of RBC from the male donors not supplemented with oral iron, the RBC volume was restored to 92% of the precollection value. The 360-ml volume of RBC collected represented 12-19% of the donor's original RBC volume. CONCLUSIONS: Male donors can safely donate 2 units of RBC and will restore a mean of 92% of their RBC volume within 1 month without iron supplementation.     

Galactokinase activity and red blood cell age

Human erythrocyte galactokinase has been studied during red cell aging. The decay rate of enzyme activity is slower than glucose-6-phosphate dehydrogenase which is used as red cell age marker. The Michaelis constants for galactose and ATPMg²⁻ of galactokinase of young cells are similar to the Km’s of the enzyme of total cells, while the Km increases in old cells. The behaviour of galactokinase during cell aging is similar to that of other erythrocyte enzymes.     

Vitamin E and red blood cell glutathione

High doses of orally administered vitamin E (1000 IU/day) have been given to ten normal volunteers. Ten control subjects received placebo. Red blood cell glutathione was significantly higher in treated subjects than in the controls (controls: 267.5 ± 15.7 μg/mL; treated: 374.8 ± 17.3 μg/mL). These findings could be explained by an increase of glutathione synthesis brought about by the stimulation of glutathione synthetase activity. An alternative possibility is a reduced utilization of glutathione for the detoxification of free radicals. These two mechanisms could be effective in counteracting the glutathione content feedback of the synthetizing enzymes.     

Overcoming blood shortages: red blood cell and platelet substitutes and membrane modifications

Blood shortages are increasingly common as the donor base declines and extensive restrictions on blood donation disqualify many donors. Red blood cell (RBC) and platelet substitutes have long been anticipated as alternatives to standard transfusions. However, difficulties in manufacturing, efficacy, and safety have slowed the development of these products. New understanding of the relationship between blood viscosity, oxygen transport, and vasoactivity have led to more effective RBC substitutes, several of which are in advanced clinical trials. In addition, creative approaches to RBC membrane modification, such as the enzymatic cleavage of ABH glycoproteins, may lead to a universal RBC. Advances in the understanding of platelet membrane behavior at low temperatures may lead to extended platelet storage at refrigerator temperatures. Standard transfusions of human RBCs and platelets will not be replaced soon. However, these new products will be a useful alternative for selected clinical applications and will lessen our dependence on our marginally adequate blood supply.     

Mechanism of red blood cell aging: Relationship of cell density and cell age

The human red cell has a life span of 120 days. The mechanism that determines cell removal from the circulation with such precision remains unknown. Most studies of red cell aging have been based on analysis of cells of progressively increasing age separated by density. The relationship between red cell age and density has been recently challenged, and the hypothesis has been put forward that cell death is not the result of a progressive deterioration of essential cell constituents. This theory was based on preliminary observations in transient erythroblastopenia of childhood, which could not later be confirmed. When the relationship between cell aging and increasing density is critically reviewed, it appears to be based on firm experimental evidence, confirmed by in vivo demonstration of decreasing survival of cells of increasing age. Analysis of studies using buoyant density gradients reveals that this technique can easily distinguish the single exponential slope of decline for those cell components that change progressively throughout the red cell life span from the biphasic decline of those that decrease drastically at the reticulocyte-mature red cell transition. The view that the aging of the red cell and its removal from the circulation result from a progressive series of events during the 120 days of its life span appears to be the most consistent with the available data. Density separation, validated by much experimental evidence, remains a most useful technique for the study of the mechanism of aging of the red cell. © 1993 Wiley-Liss, Inc.     

Red blood cell membrane disorders

The recent discovery of the specific molecular defects in many patients with hereditary spherocytosis and hereditary elliptocytosis/pyropoikilocytosis partially clarifies the molecular pathology of these diseases. HE and HPP are caused by defects in the horizontal interactions that hold the membrane skeleton together, particularly the critical spectrin self-association reaction. Single gene defects cause red cells to elongate as they circulate, by a unknown mechanism, and are clinically harmless. The combination of two defective genes or one severe alpha spectrin defect and a thalassaemia-like defect in the opposite allele (alphaLELY) results in fragile cells that fragment into bizarre shapes in the circulation, with haemolysis and sometimes life-threatening anaemia. A few of the alpha spectrin defects are common, suggesting they provide an advantage against malaria or some other threat. HS, in contrast, is nearly always caused by family-specific private mutations. These involve the five proteins that link the membrane skeleton to the overlying lipid bilayer: alpha and beta spectrin, ankyrin, band 3 and protein 4.2. Somehow, perhaps through loss of the anchorage band 3 provides its lipid neighbours (Peters et al, 1996), microvesiculation of the membrane surface ensues, leading to spherocytosis, splenic sequestration and haemolysis. Future research will need to focus on how each type of defect causes its associated disease, how the spleen aggravates membrane skeleton defects (a process termed 'conditioning'), how defective red, cells are recognized and removed in the spleen, and why patients with similar or even identical defects can have different clinical severity. Emphasis also needs to be given to improving diagnostic tests, particularly for HS, and exploring new options for therapy, like partial splenectomy, which can ameliorate symptoms while better protecting patients from bacterial sepsis and red cell parasites, and perhaps from atherosclerosis (Robinette & Franmeni, 1977) and venous thrombosis (Stewart et al, 1996).