Reduced red cell mass is a poor prognostic indicator in chronic kidney disease (CKD) patients. Whilst overt anaemia impacts on the quality of life of patients with CKD, lowered red cell mass may also compromise oxygen delivery to proximal tubular cells and contribute to progressive kidney injury. Epidemiological data from cats with CKD support this hypothesis although controlled interventional studies involving drugs that raise red cell mass in trials designed to test this hypothesis are lacking in both human and veterinary medicine. Recombinant analogues of erythropoietin (EPO) are currently standard of care for human CKD patients where low red cell mass impacts on their quality of life. Resistance to EPO is encountered in 20% to 40% of patients treated, probably due to functional iron deficiency, reflecting the difficulties of managing iron deficiency associated with the chronic inflammation of CKD. Similar issues are likely faced in managing anaemia in feline CKD although published data on the use of human EPO analogues are limited as such treatment in cats risks antibody formation resulting in red cell aplasia and transfusion dependency and so is reserved for late stage cases only. This article reviews the recent alternative therapeutic approach to increase red cell mass using HIF-prolyl hydroxylase inhibitors and explains their mode of action and theoretical advantages over EPO analogues in the context of iron metabolism. The results of human clinical trials and the potential benefit of adopting this approach in feline CKD patients are discussed.

Patients with end-stage renal disease (ESRD) under hemodialysis (HD) are at greater risks of infectious spondylitis (IS), but there is no reliable predictor that facilitate early detection of this relatively rare and insidious disease.
A retrospective review of the medical records from patients with ESRD under HD over a 12-year period was performed at a tertiary teaching hospital, and those with a first-time diagnosis of IS were identified. A 1:4 propensity score-matched case-control study was carried out, and baseline characteristics, underlying diseases, and laboratory data were compared between the study group and the control group, one month before the date of diagnosis or the index date respectively.
A total of 16 patients with IS were compared with 64 controls. After adjustment, recent access operation (odds ratio [OR], 13.27; 95% confidence interval [CI], 3.53 to 49.91; p <  0.001), degenerative spinal disease (OR, 12.87; 95% CI, 1.89 to 87.41; p = 0.009), HD through a tunneled cuffed catheter (OR, 6.75; 95% CI, 1.74 to 26.14; p = 0.006), low serum levels of hemoglobin, albumin, as well as high levels of red blood cell volume distribution width (RDW), alkaline phosphatase (ALP), and high sensitivity C-reactive protein were significant predictors for a IS diagnosis one month later. Receiver operating characteristic curves for hemoglobin, RDW, ALP, and albumin all showed good discrimination. The further multivariate models identified both high serum ALP levels and low serum RDW levels following a recent access intervention in patients with relatively short HD vintages may be indicative of the development of IS.
Patients under HD with relatively short HD vintages showing either elevated ALP levels or low RDW levels following a recent access intervention should prompt clinical awareness about IS for timely diagnosis.

Severe exercise-associated hyponatremia (EAH) is largely dilutional, whereas contributions of sodium loss remain equivocal. We present a case of EAH with encephalopathy involving an experienced male cyclist with no recollection of the event. We thereby conducted a retrospective analysis of biochemical trajectories during hospital recovery. The normalization of serum [Na], in context with changes in other variables, offered a \'reverse\' perspective of the underlying pathophysiology. The following biochemical changes were temporally observed, with the return of normonatremia: 1) a decrease in serum potassium and calcium concentrations (absence of extracellular fluid dilution); 2) a decrease in total protein, blood urea nitrogen, hematocrit and hemoglobin (plasma volume expansion); and 3) an increase in mean platelet and red cell corpuscular volumes (cellular expansion after total body water and sodium deficits). Collectively, these temporal changes provide biochemical evidence suggesting that this patient\'s severe symptomatic EAH was associated with volume depletion from underreplaced sodium losses.

A revolutionary advance in ecological immunology is that postgenomic technologies now allow molecular mediators defined in laboratory models to be measured at the mRNA level in field studies of many naturally occurring species. Here, we demonstrate the application of such an approach to generate meaningful immunological profiles for wild mammals. We sampled a natural field vole population across the year (n = 307) and developed a battery of cellular assays in which functionally different pro- and anti-inflammatory signalling responses (transcription factors and cytokines) were activated and quantified by Q-PCR. Temporal trends were the strongest feature in the expression data, although some life history stages (mating vs. nonmating males and pregnant females) were also associated with significant variation. There was a striking set of significant negative associations between inflammatory mediators and condition indices reflecting packed erythrocyte volume and relative liver size, spleen size and splenocyte count. Grouped (principal component) measures of inflammatory and anti-inflammatory expression were high in winter, with minima in the breeding season that occurred earlier for grouped anti-inflammatory responses than for grouped inflammatory responses. Some individual immunological mediators also showed patterns unrelated to the breeding season or annual periodic cues. For example, interferon regulatory factor 5 (IRF5) expression declined throughout the study period, indicating a systematic trend in antimicrobial defences. Pinpointing the causes and consequences of such variation may help identify underlying environmental drivers of individual fitness and demographic fluctuation.

A patient of 31 years of age with an atypical overhydrated hereditary stomatocytosis is described. The diagnosis was established on the basis of a markedly increased red cell volume with low MCHC, high osmotic fragility of red cells, but increased binding of eosin-5-maleimide (EMA) to red cells, presence of stomatospherocytes and large spherocytes in blood and a high sodium and low potassium concentration in erythrocytes. A double band 7 was found by SDS-PAGE of the erythrocyte membrane, but even when only one them was taken into account, the level of stomatin was normal. Expression of stomatospherocytes in patient\'s blood was erratic: in blood films prepared in 2005, both stomatospherocytes and large spherocytes were present but in those from 2008 large erythrocytes of spherocyte morphology predominated. Clinically, the disease symptoms were typical for haemolytic anemia. When heparinized blood of the patient was kept at 0 degrees Celsius for 24 h, the haemolysis of red cells amounted only to 2%. The patient\'s son, 5 years old, suffers from the same disease.
CONCLUSIONS: In spite of its rarity, hereditary stomatocytosis and allied disorders should be taken into consideration in differential diagnosis of haemolytic anemia including newborns. The diagnosis is supported by finding increased binding of eosin-5-maleimide (EMA) dye to patients\' erythrocytes associated with their elevated osmotic fragility. Absence of a significant count of stomatocytes in the blood does not exclude the diagnosis of overyhydrated hereditary stomatocytosis.

The present study was designed to determine the effect of anisocytosis on the association of MCV values with HbA1c and reticulocyte counts as markers of red cell age. Normo-, micro- and macrocytic samples, fractionated by counterflow centrifugal elutriation were studied. The previously described correlation between MCV and HbA1c was only observed in normal samples and in the middle fractions of samples with anisocytosis. At both extremes of the elutriation profile, curves for HbA1c content and reticulocyte count levelled out. Furthermore, in fractions containing the largest red cells of the microcytic series and the smallest red cells of normo- and macrocytic samples, reticulocyte count decreased while HbA1c content increased with increasing MCV. From these data it is concluded that MCV is not an absolute determinant of red cell age in case of anisocytosis.

When microcytosis is present in patients with anemia of chronic disease, the mean corpuscular volume (MCV) rarely if ever falls below 70 fL. The lowest MCV previously reported is 67 fL. We describe a patient with anemia of chronic disease with severe microcytosis and an MCV of 61 fL. After correction of the chronic disorder, complete correction of the hematologic values occurred. In patients with a low total iron binding capacity, iron therapy should not be instituted without clearly establishing the presence of iron deficiency irrespective of the degree of microcytosis.

A case of posttransplant erythrocytosis in a 51-year-old diabetic man is described. This problem, which can occur in 5 to 15% of renal transplant patients, can result from a contracted plasma volume (diuretics, pressure natriuresis, or glycosuria) or from a true elevation in red blood cell mass. Once the diagnosis of true erythrocytosis is made by a radiolabeled red blood cell mass study, secondary causes such as hypoxia, liver disease, polycythemia rubra vera, renal artery stenosis, and cystic kidney disease should be excluded. Posttransplant erythrocytosis has only been observed in renal transplant recipients and appears to be more frequent with cyclosporine compared with azathioprine therapy. An inappropriately high level of erythropoietin has been described in some, but not all patients, suggesting stimulation of erythropoietin production as the mechanism. Posttransplant erythrocytosis can be associated with an increased incidence of thrombotic events. The presence of this potential complication has prompted intervention to maintain the hematocrit below 50 to 55%. Measures such as discontinuation of diuretics as well as better control of blood pressure and plasma glucose should be used to facilitate the correction of extracellular volume contraction. Phlebotomy has been the most accepted intervention to intermittently lower the hematocrit when needed, but this can lead to iron deficiency. Newer therapeutic modalities are now being used to treat the problem medically. Theophylline, which reduces adenosine-mediated erythropoietin synthesis, is effective but may be associated with side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Despite published guideline and consensus conference recommendations, the role of acute preoperative hemodilution in elective surgery has not been defined. We performed a case study analysis of this technique in a large surgical program in order to estimate its degree of efficacy as practiced routinely, and to better define its role as a blood conservation strategy. Patients undergoing elective radical prostatectomy by one surgeon during a 3-yr period were analyzed retrospectively for blood loss, hematocrit levels, records of acute hemodilution, and transfusion outcomes. Patient blood volumes were determined by nomogram; final hematocrits after discrete blood volumes lost by surgery or by hemodilution were estimated. Sixteen (4.4%) of 410 total patients reviewed underwent hemodilution, representing 0 (0%), 4 (3%), and 12 (8%) of the 112, 146, and 152 patients undergoing surgery in years 1, 2, and 3, respectively. Median whole blood volume and mean red blood cell (RBC) volume removed by hemodilution was 1000 mL (range, 400-1500 mL) and 338 mL (range, 156-585 mL), respectively, representing 15% of patients\' admission RBC volume. Net intraoperative RBC volume \"saved\" in losses by this technique was 95 mL (range, 25-204 mL), representing only 9.3% (range, 4%-17%) of total RBC volume lost during hospitalization. RBC volume removed by hemodilution constituted 34% (95-283 mL) of the total RBC volume transfused. We conclude that use of acute preoperative hemodilution remains in evolution and, as a single blood conservation intervention, contributes only modestly to blood conservation.

A 67-year-old woman with agnogenic myeloid metaplasia, who underwent splenectomy 1 year after the diagnosis, experienced spontaneous hematologic remission 6 years after splenectomy. Ten months before her anemia improved, peripheral leukocytes no longer showed a shift to the left and peripheral erythroblasts had disappeared. Sequential erythrokinetic studies revealed ineffective erythropoiesis with mild hemolysis and expansion of marrow activity in the tibia and femur but no erythropoiesis in the sacral or vertebral marrow.