Large Red Blood Cells Research Articles

Computational analysis of peripheral blood smears detects disease-associated cytomorphologies

Many hematological diseases are characterized by altered abundance and morphology of blood cells and their progenitors. Myelodysplastic syndromes (MDS), for example, are a group of blood cancers characterised by cytopenias, dysplasia of hematopoietic cells and blast expansion. Examination of peripheral blood slides (PBS) in MDS often reveals changes such as abnormal granulocyte lobulation or granularity and altered red blood cell (RBC) morphology; however, some of these features are shared with conditions such as haematinic deficiency anemias. Definitive diagnosis of MDS requires expert cytomorphology analysis of bone marrow smears and complementary information such as blood counts, karyotype and molecular genetics testing. Here, we present Haemorasis, a computational method that detects and characterizes white blood cells (WBC) and RBC in PBS. Applied to over 300 individuals with different conditions (SF3B1-mutant and SF3B1-wildtype MDS, megaloblastic anemia, and iron deficiency anemia), Haemorasis detected over half a million WBC and millions of RBC and characterized their morphology. These large sets of cell morphologies can be used in diagnosis and disease subtyping, while identifying novel associations between computational morphotypes and disease. We find that hypolobulated neutrophils and large RBC are characteristic of SF3B1-mutant MDS. Additionally, while prevalent in both iron deficiency and megaloblastic anemia, hyperlobulated neutrophils are larger in the latter. By integrating cytomorphological features using machine learning, Haemorasis was able to distinguish SF3B1-mutant MDS from other MDS using cytomorphology and blood counts alone, with high predictive performance. We validate our findings externally, showing that they generalize to other centers and scanners. Collectively, our work reveals the potential for the large-scale incorporation of automated cytomorphology into routine diagnostic workflows.

Hyper high haemoglobin content in red blood cells and erythropoietic transitions postnatally in infants of 22 to 26 weeks’ gestation: a prospective cohort study

ObjectiveBlood cell populations, including red blood cells (RBC) unique to the extremely preterm (EPT) infant, are potentially lost due to frequent clinical blood sampling during neonatal intensive care. Currently, neonatal...

In vitro study on the partitioning of red blood cells using a microchannel network.

To investigate the partitioning properties of red blood cells (RBCs) in the bifurcating capillary vessels, an in vitro experiment was performed to perfuse human RBC suspensions into the microfluidic channels with a width of <10μm. Two types of microchannel geometries were established. One is a single model comprising one parent and two daughter channels with different widths, and the other is a network model that had a symmetric geometry with four consecutive divergences and convergences. In addition to the fractional RBC flux at each bifurcation, changes in hematocrit levels and flow velocity before and after the bifurcation were investigated. In the single model, non-uniform partitioning of RBCs was observed, and this result was in good agreement with that of the empirical model. Furthermore, in the network model, the RBC distribution in the cross-section before the bifurcation significantly affected RBC partitioning in the two channels after the bifurcation. Hence, there was a large RBC heterogeneity in the capillary network. The hematocrit levels between the channels differed for more than one order of magnitude. Therefore, the findings of the current research could facilitate a better understanding of RBC partitioning properties in the microcirculatory system.

Inter-donor variability in deformability of red blood cells in blood units.

This study aimed to examine the donor-to-donor variability in the deformability of red blood cells (RBCs) from freshly collected blood donations (F-RBC) and packed RBCs. Packed RBCs are supplied for transfusion by the first-in-first-out (FIFO) criterion, assuming that their quality is the same for packed RBCs with equal storage duration. To challenge this notion, we determined the deformability of F-RBC and packed RBCs stored for different durations. Three RBC groups were employed: A. 79 samples of F-RBC; B. 76 samples of packed RBC units, randomly used for transfusion at different storage durations; and C. 65 samples of outdated packed RBCs stored for 35 to 37 days. All packed RBC units were non-leukofiltrated and stored in Citrate-phosphate-dextrose solution with adenine (CPDA-1). RBC deformability was determined using a computerised cell-flow properties analyser, which monitors the shape change of cells directly visualised in a narrow-gap flow chamber and provides the cells' deformability distribution in a large RBC population. The F-RBC deformability exhibited a wide-range inter-donor variability. The cold storage of packed RBCs exerted a mild reduction of deformability, which became significant, compared to the initial inter-donor variability, only after 3 weeks of storage. Packed RBCs are generally supplied for transfusion by the FIFO criterion based on the assumption that the storage duration is a key factor of RBC quality. This study demonstrates that the deformability of red blood cells is significantly different in donors, and substantial variability persists throughout the entire process of their storage. Therefore, the FIFO criterion is not sufficient for assessing the RBC deformability, which should, therefore, be specifically characterised for each unit.

In vitro Characterization and Numerical Simulations of Red Blood Cell Transmigration Through Splenic Inter-Endothelial Slits

During their circulation through the spleen, red blood cells (RBCs) are forced to squeeze through gaps between endothelial cells that are ∼8 times narrower than its diameter. The ensuing squeezing motion causes large RBC deformations that remove old and diseased cells from the circulation. There is limited data about the deformation and stress experienced by RBCs. To study the mechanics of RBC splenic filtration, we designed and characterized a family of microfluidic devices where a suspension of human RBCs flows through an array (N = 50) of channels of controlled length (L), width (W) and height (H). We varied these geometrical parameters (0.75<W<L<H2 um) RBCs reorient into the direction of less constrain, cell diameter is parallel to the height of the channel, whereas in narrower channels, cells fold into themselves (U shape) experimenting large deformations. We examined computationally the deformation and stress of these folded cell shapes under different flow rates and slit geometries. We explored the possibility of deformation-induced spectrin unfolding and dissociation, which might play an important role in pathological mechanisms of hereditary RBC membrane disorders.

Dielectrophoretic microfluidic device for separation of red blood cells and platelets: a model-based study

The paper proposes a dielectrophoresis microfluidic chip for particle separation, which uses dielectric properties to perform size-based fractionation of red blood cells and platelets. Based on the control variables, the distribution of the electric field in the chip and the trajectory of the particles in the microfluidic channel are calculated using COMSOL Multiphysics under different electrode shapes, voltages and chip exit structures. Both red blood cells and platelets respond to negative dielectrophoresis at an alternating current signal with a frequency of 100 kHz. The larger red blood cells are subjected to a stronger dielectrophoretic force than the platelets and are biased toward the right outlet, and the platelets flow out from the left outlet under the combined action of fluid force and dielectrophoretic force to achieve the purpose of separation. On this basis, through quantitative comparison and analysis, a more optimized microfluidic chip capable of effectively separating particles is finally selected.

Abstract O-05: BLOOD TRANSFUSION IN PEDIATRIC ECMO: EPIDEMIOLOGY, OUTCOMES, AND FACTORS ASSOCIATED WITH LARGE TRANSFUSION VOLUME

Aims & Objectives: Patients supported with Extracorporeal Membrane Oxygenation (ECMO) receive large volumes of red blood cell (RBC) transfusions. We aimed to describe survival and factors associated with large RBC transfusion volume during pediatric ECMO. Methods This retrospective single-center cohort study included all patients supported by ECMO for > 12 hours from January 1st, 2015 through December 31st, 2016. The primary outcome was RBC volume transfused during ECMO (ml/kg/day). Results 123 patients with median age of 0.3 (Interquartile range [IQR]: 0, 3) years were analyzed. Congenital heart disease (CHD; n=56, 46%) was the most common diagnosis. Median RBC volume transfused during ECMO was 26 (IQR 12, 46) ml/kg/day. Higher volumes were transfused during the first 24 hours (figure 1). High RBC users (>75th percentile) were more likely be supported by veno-arterial ECMO (100 vs 75%, p=0.005), have CHD (81 vs 34%, p < 0.001), and experience bleeding (33 vs 11% days, p<0.001). In multivariable linear regression analysis younger age (-7% per year, 95%Confidence Interval [CI] -9 to -5%, p<0.001), CHD (+36%, 95%CI 4–78%, p=0.03), extracorporeal cardiopulmonary resuscitation (+54%, 95%CI 18–100%, p=0.002), more blood draws per day (+6%, 95%CI 3–9%, p<0.001), and higher proportion of bleeding days (+30% per 10% increase, 95%CI 21–39%, p<0.001) were associated with larger RBC transfusion volume. Mortality was higher in those receiving large RBC transfusion volume (61 vs 36%, p=0.02) Conclusions ECMO patients exposed to large RBC transfusion volume have reduced survival. The association of bleeding and frequent laboratory testing with higher transfusion volume offers quality improvement opportunities in ECMO management.

Shift from darbepoetin-α to continuous erythropoietin receptor activator decreases serum aluminium concentration in patients on hemodialysis.

The response of erythropoietic stimulating agents (ESA) in uremic patients may be associated with the changes of biochemical parameters, metal elements and inflammation status during the shift from one ESA to another. We compared changes in above mentioned factors after switching from darbepoetin-α (DPO) 20μg weekly for 10 weeks to continuous erythropoietin receptor activator (CERA) 100μg monthly for 10 weeks in uremic patients on hemodialysis. The haematocrit (Hct), metal elements and inflammation status are the primary outcome. Subjects included 54 patients without transfusion or bleeding or additional ESAs. Responders (IR, n=36) were defined as patients with an increase in Hct after the swtich. Although there was no significant difference in overall mean Hct after the switch (p=0.135), there are significantly greater mean number of red blood cells (RBC) (p=0.006), higher platelet numbers (p=0.001), larger RBCs (p=0.017) and higher creatinine (p=0.04) and total cholesterol (T-CHOL) (p=0.003) levels. Mean overall aluminium (Al) level decreased significantly (p=0.001). C-reactive protein (CRP) also decreased (p=0.016). The overall LDH increased (p=0.049) and potassium decreased significantly (p=0.036), which indicating active erythropoiesis. The calcium (Ca) level was significantly higher (p=0.034) and phosphate was significantly lower (p=0.028) after the shift. Although there was no significant increase in overall levels of parathyroid hormone (PTH) after the shift (p=0.061), but the pre-shift and post-shift PTH level was significantly higher in IRs than in non-IRs (p=0.003 and p=0.027, respectively). IRs had a significantly lower initial T-CHOL (p=0.03) and initial CRP (p=0.012) than non-responders, which may be related to lower inflammation. We found the shift from DPO to CERA results in lower Al levels, a reduced inflammatory response, and an increase in RBC number and PTH level in uremic patients on hemodialysis.

Persistent increase in red cell size distribution width after acute diseases: A biomarker of hypoxemia?

BackgroundA biomarker of hypoxic exposure would be useful in clinical diagnosis and prognosis. Acute hypoxia stimulates large increases in serum erythropoietin (EPO), and EPO induces formation of characteristic enlarged red blood cells (RBCs). The presence of large RBCs perturbs red cell distribution width (RDW). MethodsUsing a >2M patient medical claims database, the human pathome was scanned for diseases where RDW rose 0–50days following a new diagnosis. The course of RDW after selected diagnoses was visualized by registering RDW measurements by diagnosis date. ResultsAcute hemorrhage, which provokes EPO-driven erythropoiesis, is followed by increases in RDW but not mean cell volume (MCV). Similar RDW increases follow many acute diseases with risk of hypoxia, including heart failure, pneumonia, atelectasis, pulmonary embolism, pneumothorax, and sepsis. Elevations reach maximum within 1month after onset and subside to pre-disease levels about 6months later. Unlike the case with iron-deficiency anemia (IDA), RDW elevations after hypoxia-associated diseases are unaccompanied by discernible change in average RBC size. ConclusionsAs predicted by a model risk pathway linking hypoxia to formation of enlarged RBCs via EPO, acute hypoxemia-related disease episodes induce change in RBC size distribution. Further study is needed to explore whether a more sensitive and specific signal can be extracted from the fine structure of the RBC size distribution routinely measured in automated hemocytometers.

Global analysis of induced transcription factors and cofactors identifies Tfdp2 as an essential coregulator during terminal erythropoiesis

Key transcriptional regulators of terminal erythropoiesis, such as GATA-binding factor 1 (GATA1) and T-cell acute lymphocytic leukemia protein 1 (TAL1), have been well characterized, but transcription factors and cofactors and their expression modulations have not yet been explored on a global scale. Here, we use global gene expression analysis to identify 28 transcription factors and 19 transcriptional cofactors induced during terminal erythroid differentiation whose promoters are enriched for binding by GATA1 and TAL1. Utilizing protein-protein interaction databases to identify cofactors for each transcription factor, we pinpoint several co-induced pairs, of which E2f2 and its cofactor transcription factor Dp-2 (Tfdp2) were the most highly induced. TFDP2 is a critical cofactor required for proper cell cycle control and gene expression. GATA1 and TAL1 are bound to the regulatory regions of Tfdp2 and upregulate its expression and knockdown of Tfdp2 results in significantly reduced rates of proliferation as well as reduced upregulation of many erythroid-important genes. Loss of Tfdp2 also globally inhibits the normal downregulation of many E2F2 target genes, including those that regulate the cell cycle, causing cells to accumulate in S phase and resulting in increased erythrocyte size. Our findings highlight the importance of TFDP2 in coupling the erythroid cell cycle with terminal differentiation and validate this study as a resource for future work on elucidating the role of diverse transcription factors and coregulators in erythropoiesis.

3-D Perfusion Bioreactor Process Optimization for CD34+ Hematopoietic Stem Cell Culture and Differentiation towards Red Blood Cell Lineage

Process optimization for in vitro cellular engineering of CD34+ hematopoietic stem cell (HSC) culture expansion and differentiation towards red blood cell (RBC) lineages continues to remain a multifaceted challenging operation. This work focuses on three process aspect experiments with the goal of providing improved conditions for the culture of HCSs towards RBC lineages in four-compartment hollow fiber based bioreactors. In a first set of experiments, ideal conditions for the expansion and differentiation of CD34+ HSCs into RBCs were determined by testing the impact of initial cell plating density (3,000 cells/mL versus 20,000 cells/mL), the frequency of replenishing medium, and the transfer to new wells for expansion using 2D transwell plate cultures over 28 days. Results show that a lower density of 3,000 cells/mL and more frequent media changes promote higher levels of cell expansion. In a second independent set of experiments, hollow fiber bioreactor cultures were used to assess if cell inoculation and harvest from such a bioreactor technology platform are potentially damaging HSCs, yielding unfavorable outcomes. Four 8-mL cell chamber volume laboratory scale bioreactors were inoculated with an initial HSC seeding density of 20,000 cells/mL each, perfused for 4 hours, and then harvested to determine the percent recovery. Cells were effectively recovered from the bioreactors, and in follow-up 2D conventional plate cultures the recovered cells expanded as well as the control cultures, indicating that inoculation and harvest procedures are not a source of mechanical injury or cell loss during bioreactor culture. Finally, a third independent set of experiments used multiple 8-mL laboratory scale bioreactors with an initial HSC seeding density of 20,000 cells/mL. Cells were cultured at three time intervals for 8 to 11 days (n=10), 12 to 14 days (n=15), or 15 to 22 days (n=3) with fold-expansion results of 106.0 ± 94.0, 999.5 ± 589.6, and 456.3 ± 33.6, respectively. Although additional studies are necessary for complete large scale-up RBC optimization, the results of these studies have led to a methodical understanding of improved conditions for HSC culture in hollow fiber perfusion bioreactor systems.

Investigation of Blood Flow Analysis and Red Blood Cell Aggregation

This work aims to develop a method for quantitatively analyzing red blood cell (RBC) aggregates under controlled flow conditions. Images of experiments are captured and processed in order to quantify aggregation. The experimental setup consists of RBC suspensions in blood plasma entrained by a phosphate-buffered saline solution in a 110 × 60μm polydimethylsiloxane microchannel. The experiments are performed by varying the hematocrit (5, 10, and 15%) and the flow rate (Q=5 and 10μl/hr) in order to observe the effect of shear rate on RBC aggregation. Microchannel dimensions as well as fluid flow rates are determined using numerical simulations. The flow is visualized using a highspeed camera coupled to a micro particle image velocimetry system. Videos obtained with the high-speed camera are processed using a MATLAB program, with each frame analyzed separately. RBC aggregates are detected based on the image intensities and the connectivity between RBCs, using image processing techniques. The average aggregate size and distribution of RBCs for various aggregate sizes are determined for each of the shear rates and hematocrits. These aggregates are shown to be larger at low flow rates where the shear rate is small. Results from tests performed at high hematocrits also show larger RBC aggregates.

Transfusion practice varies widely in cardiac surgery: Results from a national registry

Evidence is accumulating of adverse outcomes associated with transfusion of blood components. Ifthere are differences in perioperative transfusion rates in cardiac surgery, and what hospital factors may contribute, requires further investigation. Analysis of 42,743 adult patients who underwent 43,482 procedures from 2005 to 2011 at 25Australian hospitals, according to the Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database. Multiple logistic regression examined associations of patient and hospital characteristics with transfusion of ≥1 red blood cell (RBC) unit; platelet (PLT), fresh frozen plasma (FFP), and cryoprecipitate (CRYO) doses; and ≥5 RBC units, from surgery until hospital discharge. Procedures included 24,222 (55%) isolated coronary artery bypass grafts, 7299 (17%) isolated valve, 4714 (11%) coronary artery bypass graft and valve, and 7247 (17%) other procedures. After adjustment for various patient and procedure characteristics, transfusion rates varied across hospitals for ≥1 RBC unit from 22% to 67%, ≥5 RBC units from 5% to 25%, ≥1 PLT dose from 11% to 39%, ≥1 FFP dose from 11% to 48% and ≥1 CRYO dose from 1% to 20%. Hospital characteristics, including state or territory, private versus public, and teaching versus nonteaching, were not associated with variation in transfusion rates. Variation in transfusion of all components and large volume RBC was identified, even after adjustment for patient and procedural factors known to influence transfusion, and this was not explained by hospital characteristics.

Two Distinct Genetic Mechanisms Modify the Level of HbA2 in Peripheral Blood,

Abstract 3193The switch from embryonic to fetal hemoglobin (HbF, α2γ2) in utero, and from fetal to adult hemoglobin at birth is well documented and achieved by the sequential activation of ε, γ and δ/β genes at the β globin gene (HBB) cluster. A change in the expression of hemoglobin genes also take place in adult erythropoiesis: earlier erythroid progenitors have been shown to produce significant amounts of fetal hemoglobin, while the more mature progenitors contain essentially none. In keeping with the sequential activation of β-like globin genes, δ globin chain synthesis also declines as maturation in erythroid progenitors progresses. Understanding the developmental changes of gene expression at the beta globin locus is not purely of academic interest, since a therapeutic induction of HbF or HbA2 (α2δ2) production would be of significant clinical benefit for patients with a defect of HbA (α2β2) function or abundance, such as sickle cell disease or β thalassemia. We have previously studied the genetic regulation of fetal hemoglobin persistence in a genome-wide association study (GWAS) in healthy volunteers, and are now extending this approach to the study of HbA2.Our study population is the 'Twins UK' twin registry of healthy Europeans, mostly female adult individuals, with genome-wide single polymorphisms (SNP) data and hemoglobin phenotypes for a primary study group (n=2,340) and a second replication group (n=1,880). A quantitative trait GWAS analysis was carried out to assess the relationship between SNPs and the HbA2 trait.We found that HbA2 (as a percentage of total hemoglobin) was weakly, but significantly, correlated with the amount of fetal hemoglobin carrying cells (F cells) an individual possesses (r = 0.14, p < 0.01). This suggests the existence of some common biological process that influences both hemoglobin species. We also found that the same SNP alleles at chromosome 6q23.3 (HBS1L-MYB, peak signal rs7775698, p = 2.51×10−9) that are associated with a boost in the prevalence of F cells and larger red blood cells (denoted by the mean cell volume or MCV) also promote HbA2 levels, again pointing to some common biological factor connected with the erythropoietic maturation process.Interestingly, neither of the other two major HbF loci, BCL11A on chromosome 2p, or the HbF-promoting regions within the HBB cluster (at the β LCR and the γ globin genes) on chromosome 11p, showed association with HbA2 levels. Instead, SNPs around the β globin gene itself (clearly separate also from the delta gene) exert a significant influence on HbA2 levels (peak association rs12793110, p=5.11×10−12) (see Figure 1). In contrast to the HBS1L-MYB region on chromosome 6, the HbA2-boosting alleles at these SNPs do not increase red blood cell MCV. We propose that the SNPs around HBB influences HbA2 (ie. δ globin gene) expression via a mechanism that is related to the competitive process between the β and δ gene expression that might mimic a very mild β thalassemic effect. [Display omitted] We propose that the systematic genetic study of specialized hematological traits in healthy volunteers can help to understand the biology of hematopoiesis. Disclosures:No relevant conflicts of interest to declare.

Photon-cell interactive Monte Carlo model based on the geometric optics theory for photon migration in blood by incorporating both extra- and intracellular pathways

A photon-cell interactive Monte Carlo (pciMC) that tracks photon migration in both the extra- and intracellular spaces is developed without using macroscopic scattering phase functions and anisotropy factors, as required for the conventional Monte Carlos (MCs). The interaction of photons at the plasma-cell boundary of randomly oriented 3-D biconcave red blood cells (RBCs) is modeled using the geometric optics. The pciMC incorporates different photon velocities from the extra- to intracellular space, whereas the conventional MC treats RBCs as points in the space with a constant velocity. In comparison to the experiments, the pciMC yielded the mean errors in photon migration time of 9.8±6.8 and 11.2±8.5% for suspensions of small and large RBCs (RBC(small), RBC(large)) averaged over the optically diffusing region from 2000 to 4000 μm, while the conventional random walk Monte Carlo simulation gave statistically higher mean errors of 19.0±5.8 ( p < 0.047) and 21.7±19.1% (p < 0.055), respectively. The gradients of optical density in the diffusing region yielded statistically insignificant differences between the pciMC and experiments with the mean errors between them being 1.4 and 0.9% in RBC(small) and RBC(larger), respectively. The pciMC based on the geometric optics can be used to accurately predict photon migration in the optically diffusing, turbid medium.

Increased red blood cell aggregation in patients with Gaucher disease is non-inflammatory

Red blood cell (RBC) aggregation is enhanced in the presence of ongoing inflammation, because of plasma protein effects, especially fibrinogen. Large RBC aggregates, in addition to being a marker of systemic inflammation, may hinder tissue perfusion and oxygenation. Gaucher disease, the most common lysosomal storage disorder, evinces many of the hallmarks of chronic inflammation. Manifestations of Gaucher disease which may be related to microvascular occlusion include avascular necrosis (AVN), bone crisis, and pulmonary hypertension. This study aims to determine whether increased RBC aggregation in non-splenectomized patients with Gaucher disease is due to Gaucher-related inflammation. The Cell Flow Properties Analyzer (CFA) monitors blood under conditions of different shear stress by creating varying pressure gradients. Blood from non-splenectomized patients with Gaucher disease showed only a slight correlation between aggregation parameters and fibrinogen levels, whereas blood from non-splenectomized patients treated with enzyme replacement therapy (ERT) showed marked correlation between aggregation parameters and fibrinogen, as in the control group. These results underscore the hypothesis that RBC aggregation in Gaucher disease is increased by (at least) two mechanisms: a fibrinogen-mediated inflammatory process and another non-inflammatory process that may be induced by elevated glucocerebroside levels in the RBC and/or inhibited by elevated plasma cerebroside levels.

Mesoscale Simulation of Blood Flow in Small Vessels

Computational modeling of blood flow in microvessels with internal diameter 20–500 μm is a major challenge. It is because blood in such vessels behaves as a multiphase suspension of deformable particles. A continuum model of blood is not adequate if the motion of individual red blood cells in the suspension is of interest. At the same time, multiple cells, often a few thousands in number, must also be considered to account for cell-cell hydrodynamic interaction. Moreover, the red blood cells (RBCs) are highly deformable. Deformation of the cells must also be considered in the model, as it is a major determinant of many physiologically significant phenomena, such as formation of a cell-free layer, and the Fahraeus-Lindqvist effect. In this article, we present two-dimensional computational simulation of blood flow in vessels of size 20–300 μm at discharge hematocrit of 10–60%, taking into consideration the particulate nature of blood and cell deformation. The numerical model is based on the immersed boundary method, and the red blood cells are modeled as liquid capsules. A large RBC population comprising of as many as 2500 cells are simulated. Migration of the cells normal to the wall of the vessel and the formation of the cell-free layer are studied. Results on the trajectory and velocity traces of the RBCs, and their fluctuations are presented. Also presented are the results on the plug-flow velocity profile of blood, the apparent viscosity, and the Fahraeus-Lindqvist effect. The numerical results also allow us to investigate the variation of apparent blood viscosity along the cross-section of a vessel. The computational results are compared with the experimental results. To the best of our knowledge, this article presents the first simulation to simultaneously consider a large ensemble of red blood cells and the cell deformation.

Intraspecific allometry of haematological parameters in Basilichthys australis

Allometry of haematological parameters (haematocrit, erythrocyte number, mean cell volume and haemoglobin concentration) of Basilichthys australis, suggested that small individuals and juveniles had larger red blood cells, less haemoglobin per volume of blood, and more diluted plasma than large and mature animals.

Red Blood Cells: Centerpiece in the Evolution of the Vertebrate Circulatory System

All vertebrates except cold-water ice fish transport oxygen via hemo-globin packaged in red blood cells (RBCs). Vertebrate RBCs vary in size by thirty-fold. Differences in RBC size have been known for over a century, but the func-tional significance of RBC size remains unknown. One hypothesis is that largeRBCs are a primitive character. Agnathans have larger RBCs than do mammals.However, the largest RBCs are found in urodele amphibians which is inconsistentwith the hypothesis that large RBCs are primitive. Another possibility is that smallRBCs increase blood oxygen transport capacity. Blood hemoglobin concentration([Hb]) and mean RBC hemoglobin concentration (MCHC) increase from Agnathato birds and mammals. However, the changes in [Hb] and MCHC do not parallelchanges in RBC size. In addition, RBC size does not affect blood viscosity. Thus,there is no clear link between RBC size and oxygen transport capacity. We hy-pothesize that RBC size attends changes in capillary diameter. This hypothesis isbased on the following observations. First, RBC width averages 25% larger thancapillary diameter which insures cell deformation during capillary flow. Function-ally, RBC deformation minimizes diffusion limitations to gas exchange. Second,smaller capillaries are associated with increased potential for diffusive gas ex-change. However, smaller capillaries result in higher resistances to blood flowwhich requires higher blood pressures. We propose that the large capillary di-ameters and large RBCs in urodeles reflect the evolutionary development of apulmonary vascular supply. The large capillaries reduced systemic vascular resis-tances enabling a single ventricular heart to supply blood to two vascular circuits,systemic and pulmonary, without developing high pressures on the pulmonary side.The large RBCs preserved diffusive gas exchange efficiency in the large capillaries.

Influence of academic examination stress on hematological measurements in subjectively healthy volunteers

Some recent reports showed that a brief exposure to a mental stressor during 3–20 min may induce hematological changes in humans. The aim of the present study was to examine the effects of academic examination stress on erythron variables, such as the number of red blood cells (RBC), hemoglobin (Hb), hematocrit (Ht), mean corpuscular volume (MCV), mean cell Hb (MCH), mean cell Hb concentration (MCHC), RBC distribution width (RDW), and serum iron and transferrin (Tf). The above variables were determined in 41 students in three conditions, i.e. the stress condition (the day before a difficult oral exam) and two baseline conditions, i.e. a few weeks earlier and later. At the same occasions, subjects completed the Perceived Stress Scale (PSS), the state version of the State-Trait Anxiety Inventory (STAI) and the Profile of Mood States (POMS). Academic examination stress significantly increased Ht, Hb, MCV, MCH and MCHC and significantly decreased RDW. There were significant relationships between the stress-induced changes in the PSS, STAI and POMS scores and those in Ht, Hb, MCV and MCH (all positive) and RDW (negative). It is concluded that academic examination stress induces significant hematological changes indicative of an increased number of large RBC and increased hemoglobinisation, which cannot be explained by shifts of fluid out of the intravascular space, concentrating non-diffusible blood constituents.