Red blood cell distribution width index in some hematologic diseases

The red blood cell distribution width index (RDW) was determined in a group of anemic male patients and normal male blood donors. Elevated mean RDW values were found in the anemic patients, with the highest value seen in sickle cell anemia, sickle cell-beta thalassemia, sickle cell trait, beta-thalassemia trait, and iron deficiency in decreasing order of magnitude. The mean RDW of the normal male subjects was 11.3. It was found that the RDW was proportional to the reticulocyte count, with the highest values in the patients with the highest reticulocyte count (sickle cell anemia). One clinical value of the RDW therefore may lie in its capacity for reflecting active erythropoiesis. For example, patients with normal or near-normal hemoglobin and with high RDWs may be suspected of having an elevated reticulocyte count that may indicate a hemoglobinopathy, such as sickle cell trait or thalassemia trait.     

Red blood cell fragmentation. Improved detection and identification of causes

The peripheral blood film and the red blood cell size distribution histogram were examined for evidence of red blood cell fragments in 2,350 subjects. To distinguish subjects with greater than or equal to 10 fragments/1,000 red blood cells (abnormal) from normal, examination of the blood film was 0.83 sensitive and 0.30 specific, whereas examination of the histogram was 0.97 sensitive and 0.87 specific. The most common causes of abnormal fragmentation were malignancy with cytotoxic chemotherapy and severe iron deficiency. In two subjects, an abnormal red blood cell fragmentation pattern was the clue to a spectrin mutant in subjects with an automated blood count previously evaluated as normal. The data suggest two conclusions: the red blood cell volume histogram appears more accurate than the peripheral blood film for routine identification of red blood cell fragments; and asymptomatic spectrin abnormality identifiable by abnormal histogram may be a relatively common disorder.     

Red blood cell proteomics

Since its discovery in the 17th century, the red blood cell, recognized in time as the critical cell component for survival, has been the focus of much attention. Its unique role in gas exchange (oxygen/CO₂ transport) and its distinct characteristics (absence of nucleus; biconcave cell shape) together with an – in essence – unlimited supply lead to extensive targeted biochemical, molecular and structural studies. A quick PubMed query with the word “erythrocyte” results in 198 013 scientific articles of which 162 are red blood cell proteomics studies, indicating that this new technique has been only recently applied to the red blood cell and related fields. Standard and comparative proteomics have been widely used to study different blood components. A growing body of proteomics literature has since developed, which deals with the characterization of red blood cells in health and disease. The possibility offered by proteomics to obtain a global snapshot of the whole red blood cell protein make-up, has provided unique insights to many fields including transfusion medicine, anaemia studies, intra-red blood cell parasite biology and translational research. While the contribution of proteomics is beyond doubt, a full red blood cell understanding will ultimately require, in addition to proteomics, lipidomics, glycomics, interactomics and study of post-translational modifications. In this review we will briefly discuss the methodology and limitations of proteomics, the contribution it made to the understanding of the erythrocyte and the advances in red blood cell-related fields brought about by comparative proteomics.     

Red blood cell substitutes and artificial blood

Artificial substitutes for specific functional portions of blood are being developed. Perfluorocarbons have received the most publicity in recent years, and one, Fluosol-DA, is undergoing clinical trials in the United States. The perfluorocarbon emulsions physically dissolve oxygen, which distinguishes them from the chemical binding that occurs in hemoglobin. Fluosol-DA has been shown to transport oxygen in amounts that are probably clinically useful if the patient inspires an atmosphere with increased oxygen. A large clinical trial from Japan suggests that Fluosol-DA is safe to transfuse, although recent work suggests that Fluosol-DA may produce significant pulmonary reactions that can be prevented by steroid administration. These reactions are probably caused by complement activation by an emulsifying agent in Fluosol-DA. Recent applications of Fluosol-DA include use in a resuscitative fluid, use in occlusive vascular disease, an special applications, such as treatment of carbon monoxide poisoning, which take advantage of the solubility properties of perfluorocarbons.     

Red blood cell transfusion strategies.

Although the hemoglobin level of 100 g/L has been used for many years as the allogeneic red blood cell (RBC) transfusion trigger, current evidence indicates that for most patients a more restrictive transfusion strategy is at least as effective as and possibly superior to a liberal transfusion strategy. Moreover, the available data indicate that the use of smaller volumes of allogeneic RBCs may be associated with decreased risk of morbidity and mortality. Thus several recent studies indicate that the use of more restrictive triggers than 100 g/L does not appear to adversely affect patient outcomes. Indeed, the majority of recently published RBC transfusion guidelines recommend a more conservative and cautious approach to allogeneic RBC transfusion practice, primarily to reduce the risk of transfusion-related adverse effects. However, the available transfusion trigger studies do not provide sufficient data to allow the claim that the improved outcomes observed are the sole result of the transfusion strategy used. It is possible that the results are the consequence of effects yet to be defined clearly. Additional studies will be necessary to determine the effects of RBC storage time and the presence of allogeneic leukocytes in allogeneic RBC transfusion practice. Nonetheless, the available data, together with detailed information about alternatives to blood product transfusions, will enable physicians to improve outcomes in transfused patients.     

Red blood cell phenotype matching for various ethnic groups

Patients requiring chronic transfusion support are at risk of alloimmunization after red blood cell (RBC) transfusion because of a disparity between donor and recipient antigen profiles. This research explored the probability of obtaining an exact extended phenotype match between blood donors randomly selected from our institution and patients randomly selected from particular ethnic groups. Blood samples from 1,000 blood donors tested by molecular method were evaluated for the predicted phenotype distribution of Rh, Kell, Kidd, Duffy, and MNS. A random subsample of 800 donor phenotypes was then evaluated for the probability of obtaining an exact match with respect to phenotype with a randomly selected patient from a particular ethnic group. Overall, there was a greater than 80 percent probability of finding an exact donor-recipient match for the K/k alleles in the Kell system. The probability ranged from 3 percent to 38 percent, depending on the ethnicity and disparities in phenotypic profiles, for the Rh, Kidd, Duffy, and MNS systems. A significant donor-recipient phenotype mismatch ratio exists with certain blood group antigens such that, with current routine ABO and D matching practices, recipients of certain ethnic groups are predisposed to alloimmunization.     

Red blood cell defects and malaria

Malaria is a major cause of childhood death throughout much of the tropical world. As a result, it has exerted a powerful force for the evolutionary selection of genes that confer a survival advantage. Identifying which genes are involved, and how they affect malaria risk, is a potentially useful way of exploring the host-parasite relationship. To date, some of the best-described malaria-protective polymorphisms relate to genes that affect the structure or function of red blood cells (RBC). Recent years have seen significant advances in our understanding of the importance of some of these genes, including glycophorin C (GYPC); complement receptor 1 (CR1); band 3 (SLC4A1); pyruvate kinase (Pklr); and the genes for alpha-(HBA) and beta-globin (HBB). The challenge for the future must be to convert these advances into fresh approaches to the prevention and treatment of malaria.     

Red cell aggregation in blood flow

Summary The rheological behavior of normal and pathological red cell aggregates in viscometric flow (artificial flow in cone plate chamber) is studied by direct microscopy, (rheoscopy) viscometry and photometry. Marked differences between normal and pathological blood are measured in the microrheological properties of red cell aggregates; only discreet differences are measured by blood viscometry (macrorheology). Both in normal and abnormal blood, red cell aggregation is a reversible process in the presence of adequate shear forces; their respective influences on apparent blood viscosity at low rates of shear are complex functions of shear rate, shear time, hematocrit and plasma viscosities. Pathological red cell aggregation (RCA) forms more rapidly and extensively than normal RCA. The pathological aggregates frequently have a tendency to grow at low rates of shear and they are highly shear resistant.Supported by Deutsche Forschungsgemeinschaft     

Red blood cell alloimmunization complicating plasma transfusion

Well-known adverse effects of plasma transfusion include viral transmission, allergic complications, and rare anaphylactic reactions. In making clinical decisions to transfuse plasma, a seldom-considered complication is that of red blood cell (RBC) alloimmunization. The authors report a patient in whom strong IgM and IgG anti-E and weak IgG anti-JKa RBC antibodies developed 15 days after infusion of two units of fresh-frozen plasma for volume expansion. These antibodies are potentially hemolytic. This case underscores the importance of considering risks of plasma infusion. Plasma should not be used casually, especially for indications for which alternate therapies, such as crystalloid and colloid solutions, are available.     

Red blood cell distribution width is associated with myocardial injury in non-ST-elevation acute coronary syndrome

OBJECTIVES:

The red blood cell distribution width has been associated with an increased risk of cardiovascular events. In the present study, we assessed the relationship between red cell distribution width values and cardiac troponin I levels in patients admitted with non-ST-elevation acute coronary syndrome.

METHODS:

We analyzed blood parameters in 251 adult patients who were consecutively admitted to the intensive coronary care unit with non-ST-elevation acute coronary syndrome over a 1-year period. For all patients, a baseline blood sample was collected for routine hematological testing. Cardiac troponin I was measured at baseline and after 6 h. The patients were diagnosed with non-ST-elevation myocardial infarction or unstable angina based on the elevation of cardiac troponin I levels.

RESULTS:

The red cell distribution width was higher in the group with non-ST-elevation myocardial infarction compared with the patient group with unstable angina (14.6±1.0 vs 13.06±1.7, respectively; p = 0.006). Coronary thrombus was detected more frequently in the group of patients with non-ST-elevation myocardial infarction than in the patients with unstable angina (72% vs 51%, respectively; p = 0.007). Using receiver operating characteristic curve analysis for the prediction of non-ST-elevation myocardial infarction based on the red cell distribution width, the area under the curve was 0.649 (95% confidence interval: 0.546-0.753; p = 0.006), suggesting a modest model for the prediction of non-ST-elevation myocardial infarction using the red cell distribution width. At a cut-off value of 14%, the sensitivity and specificity of the red cell distribution width were 73% and 59%, respectively. Additionally, the red cell distribution width was positively correlated with cardiac troponin I (r = 0.19; p = 0.006).

CONCLUSION:

A greater baseline red cell distribution width value was associated with myocardial injury and elevated cardiac troponin I levels in non-ST-elevation acute coronary syndrome. Therefore, the red cell distribution width could be considered for risk stratification of acute coronary syndrome patients admitted to emergency departments.     

Red blood cell abnormalities in cardiac valvular disease

Nineteen patients with morphological abnormalities of the red blood cells are described, and these formed approximately 3% of the total cases of cardiac valvular disease. In two patients the abnormal blood film developed after the insertion of an aortic and mitral valve prosthesis respectively, but in another two patients the abnormal blood film was corrected by aortic valve surgery. Anisopoikilocytosis may have been associated with microangiopathic haemolytic anaemia in one patient, but in the others the cardiac valvular disease was severe and other mechanical factors were not present. The mitral valve was involved in 16 patients and the aortic valve in eight.Elliptocytosis was the only abnormality in 11 blood films, schistocytes and burr cells were present in seven, and in three there were a few microspherocytes. Family studies in seven patients produced evidence of hereditary elliptocytosis in three.Anaemia was present in only two patients. One of these had infective endocarditis, and the other developed overt haemolytic anaemia following the replacement of a diseased mitral valve by a Starr-Edwards prosthesis. In this latter case there was a transiently positive direct antiglobulin test, and the anaemia and abnormal blood picture were corrected without further surgical treatment. Haemolytic anaemia did not develop in 23 patients after the insertion of an aortic valve prosthesis or homograft.Indirect evidence of haemolysis was obtained in some patients who were not anaemic. There was a reticulocytosis in one third and serum haptoglobins were decreased or absent in over half of the patients tested.     

An evaluation of some factors important for maximising sensitivity of plant virus detection by immuno-electron microscopy

We report the results of a comparison of the variations to the basic technique developed by Derrick and called 'serologically specific electron microscopy' by him. We have found that the reaction time of the antibody-coated grid with the virus preparation (virus acquisition time) is one of the key factors in determining the efficiency of the method at trapping virus particles. The lower the virus concentration, the longer the reaction time should be. The use of protein A to pretreat the grids before coating with antiserum did not appear to be of benefit under our conditions.     

Red blood cell copper,zinc superoxide dismutase activity is higher in Alzheimer's disease and is decreased by D-penicillamine

We investigated the activation of the secondary somatosensory cortex (SII) in three patients with unilateral psychogenic sensory loss in the hand. Somatosensory evoked magnetic fields were recorded in response to tactile stimulation of the index finger of the affected and the unaffected hand. Brain sources were estimated by magnetic source imaging. In all subjects, responses in both the contralateral primary somatosensory (SI) and bilateral SII areas were normal as compared with a healthy control group, irrespective of the stimulated side. The results extend previous findings of normal evoked activity in SI.     

Red cell-linked antibody assay for detection of antigenic markers on cell surfaces.

A direct method for demonstrating antigenic markers on cell surface has been developed which makes use of the ability of bovine red blood cells coated with protein A of Staphylococcus aureus (ES) to binding IgG antibody without agglutinating. Red cell-linked rabbit IgG antibody reagents (ESA) were prepared in this way, and Ig-, IgM- and Thy-1-bearing mouse spleen and peripheral blood lymphocytes were identified by a rosette assay.     

Red blood cell glutathione peroxidase activity in multiple sclerosis

Summary Glutathione peroxidase (GSH-Px) activity of red blood cells of 23 multiple sclerosis (MS) patients (10 men and 13 women, aged 22–64 years) was examined and compared to the enzyme activity of 26 healthy persons (15 men and 11 women, aged 19–50 years). It was found that the mean GSH-Px activity was significantly higher (P<0.001) in red blood cells of MS patients (39.1±8.1 IU/g Hb) as compared to the group of healthy persons (25.9±5.2 IU/g Hb). There was no difference according to sexes in both the MS patients and the control group. The results are discussed based on the hypothesis that organic peroxides play a role in the etiology of multiple sclerosis.     

Red blood cell adenine nucleotides abnormalities in Down syndrome

The red blood cell adenine nucleotides of 20 Down Syndrome patients and 20 healthy controls were determined by a new high-performance liquid chromatography method. All patients showed increased concentrations of adenosine 5'-diphosphate (ADP) and adenosine 5'-monophosphate (AMP), while adenosine 5'-triphosphate (ATP), nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+) were within normal ranges. This alternation of the energetic charge could be partly responsible for the impairment of glucose metabolism in these patients.