Normal Hematocrit Research Articles

ESAs in Dialysis Patients

The philosopher Isaiah Berlin1 divides authors and perhaps people in general into two categories: Hedgehogs, who view the world through the lens of one defining idea, and foxes, for whom the world cannot be boiled down to a single idea. Looking at erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in chronic kidney disease (CKD), should there be a single conclusion about the safety of ESAs? In a previous editorial, I discussed the use of ESAs in nondialysis patients.2 Here, I consider their continued use for the anemia of dialysis patients. ESAs have proved effective in correcting anemia in patients with ESRD. No one relishes blithely turning the clock back to the pre-ESA era, when dialysis patients were treated with repeated blood transfusions, iron therapy, anabolic steroids, and other maneuvers; however, mortality and the rate of cardiovascular complications in the dialysis population remain high, and reducing risk would be important in improving outcomes. Randomized, controlled trials (RCTs) demonstrate there is increased risk in correcting anemia with ESAs in all patients with CKD–both dialysis and nondialysis. In the recently published Trial to Reduce Cardiovascular Endpoints with Aranesp Therapy (TREAT),3 a placebo-controlled, double-blind, randomized study comprising 4038 nondialysis patients, there was a significantly higher rate of strokes in patients who were treated with darbepoetin (hazard ratio 1.92; P < 0.001) as well as higher rates of thromboembolism and cancer-related deaths. In the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) study,4 the risk was a higher rate of mortality and cardiovascular complications in nondialysis patients targeted to a hemoglobin (Hb) level of 13.0 g/dl with epoetin-alfa (hazard ratio 1.34; P = 0.03). A higher rate of death or myocardial infarction (MI) or vascular access thrombosis was also observed in the Normal Hematocrit study.5 Meta-analyses have reached …

Can lab data be used to reduce abdominal computed tomography (CT) usage in young adults presenting to the emergency department with nontraumatic abdominal pain?

We sought to determine whether laboratory parameters could be found, predictive of a negative abdominal CT scan in young adults with nontraumatic abdominal pain. Following institutional review board approval, we evaluated CT reports of 522 patients, aged 21-35 years old, who presented to the Emergency Department with nontraumatic abdominal pain. Bivariate analyses relating ten laboratory parameters to whether the CT detected a cause for abdominal pain were conducted. A multivariate logistic regression model was then derived, with all variables in the final model significant at p < 0.05. Variables were dichotomized to yield odds ratios and 95% confidence intervals. Of the 522 patients meeting inclusion criteria, 45% had a cause for pain demonstrated by CT. Predictors of a negative CT in men were normal hematocrit and negative urine blood (p = 0.045, p = 0.016, respectively), and in women normal hematocrit, granulocyte percent, and alkaline phosphatase (p = 0.023, p = 0.039, p < 0.0001, respectively). When standard normal values were used to calculate descriptive statistics, only granulocyte percent in women had a significant confidence interval (odds ratio 2.5, confidence interval 1.6-4.0). Among the 208 women with normal granulocyte percent, the final clinical diagnosis was appendicitis, cholecystitis, and diverticulitis, in three, three, and two cases, respectively (4% combined). In summary, no laboratory test was sufficient to offer reassurance that a CT is not necessary in a young adult patient with nontraumatic abdominal pain. Alternative strategies should be considered to decrease the use of CT, and its associated radiation exposure, in young adults with nontraumatic abdominal pain.

It's Time to Compare Anemia Management Strategies in Hemodialysis

Randomized trials of intravenous (IV) iron have repeatedly demonstrated a rise in hemoglobin (Hgb), an erythropoiesis-stimulating agent (ESA) dose-sparing effect, and apparent safety. Such benefits were confirmed in a trial in hemodialysis patients with high ferritin receiving high ESA doses. But long-term randomized safety trials of IV iron have not been performed, which critics blame on IV iron manufacturers, leading some to question widespread use of IV iron to optimize Hgb and reduce ESA dose. ESAs increase risks of cardiovascular events and death when used to target higher versus lower Hgb values. Association studies report increasing risk with higher ESA doses at approved Hgb targets. Nevertheless, ESAs remain essential in dialysis practice. After early termination of the Normal Hematocrit Trial in 1996, analysis suggested IV iron was a risk factor for harm. In 2006, dangers related to ESA use were recognized. Trial results demonstrating IV iron was efficacious and ESA-sparing even at higher serum ferritin have intensified the focus on iron safety. Two principal alternatives in the management of anemia among dialysis patients are: (1) more intensive ESA dosing sparing iron dosing and (2) more intensive iron dosing sparing ESA dosing. Extended safety trials of IV iron versus no iron will become confounded by ESA dose differences between arms. Similarly higher ESA doses are associated with increased mortality risk, but trials comparing ESA doses will be confounded by Hgb differences. Rather than focus on individual products, we should perform trials comparing anemia management strategies to assess safety, efficacy, and cost.

Resistance and resilience of West African Dwarf goats of the Nigerian savanna zone exposed to experimental escalating primary and challenge infections with Haemonchus contortus

We assessed the resilience and resistance to infection with Haemonchus contortus of savanna West African Dwarf (WAD) goats from northern Nigeria. Adult male goats ( n = 32) were given an escalating immunizing infection, comprising 5 weekly infections with increasing numbers of larvae. On day (D) 56 they were segregated into low (LFEC) and high (HFEC) faecal egg count phenotypes, and within each phenotype 7 goats were treated with anthelmintic and seven received no treatment. Four goats were culled for worm counts. Fourteen additional goats acted as naïve controls until D56. All, except seven naïve, were challenged with 6000 L3 of H. contortus on D63 and culled on D81, together with the seven naïve goats. The escalating infections had no effect on body weight of the goats. Neither deworming, nor challenge infection and previous experience of infection influenced body weight post-challenge (pc). There was no effect of the escalating infection on packed cell volume (PCV) of blood cells, however, the HFEC phenotypes tended to have lower values than their LFEC counterparts and controls towards the end of immunization. Virtually all goats maintained normal PCV values (28–32%) throughout, without clinical evidence of anaemia. After challenge infection the HFEC phenotypes had significantly lower PCV than the LFEC goats and naïve controls but without other symptoms of anaemia. Anthelmintic treatment had no influence on PCV pc. The anthelmintic-treated LFEC group harboured fewer worms on D18 pc than the untreated LFEC group with the superimposed challenge. In contrast anthelmintic treatment made only a small difference to the worm burdens of the HFEC group pc. In week 7 there was a strong correlation between FEC and PCV among all the goats that experienced the immunizing infection. With anthelmintic treatment taken into account, higher FEC and lower PCV in week 7 predicted higher worm burdens at the end of the experiment, but both relationships were dependent on and differed between the anthelmintic treatment groups. Overall, we found no parasitological evidence of attenuation or loss of resistance and resilience of the Nigerian savanna WAD goat ecotype to H. contortus, suggesting that significant introgression of genes from parasite-susceptible Sahelian breeds into this WAD goat population has so far not occurred.

The FDA's Perspective on the Risk for Rapid Rise in Hemoglobin in Treating CKD Anemia

The Trial to Reduce Cardiovascular Endpoints with Aranesp Therapy (TREAT) (1) has prompted the Food and Drug Administration (FDA) to reevaluate the use of erythropoiesis-stimulating agents (ESAs) in the treatment of chronic kidney disease (CKD) anemia (2). An FDA public advisory committee meeting in 2010 is anticipated. The TREAT study reported, against placebo, minimal benefit and increased risk of ESA therapy (1). Before TREAT, Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) (3), Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin β (CREATE) (4), and Normal Hematocrit (5) studies also demonstrated either no benefit or increased risk of targeting a higher hemoglobin (Hb) concentration. Consequently, attention has shifted from the benefits of ESAs to their risks (6). Most nephrologists will be eager to receive guidance from the convened FDA panel on how to interpret these trials in terms of clinical practice. In a recent New England Journal of Medicine Perspective article, Unger et al. (2) from the FDA reviewed the evidence from TREAT and the Normal Hematocrit and CHOIR studies. Unger et al. raised again, among several factors, the issue of too rapid an increase in Hb as being an important factor in determining clinical outcomes in patients who have CKD and anemia and are treated with an ESA. Here, I examine the strength of this evidence and evaluate the FDA's emphasis on the rate of increase of Hb in ESA treatment of CKD anemia. The FDA's concern regarding the potential risk of too rapid an increase in Hb dates back to a review conducted by the Center for Biologics Evaluation and Research (CBER) in 2001 (7). The CBER performed exploratory safety analyses of the Aranesp licensing application and observed an association between Hb rate of rise >0.5 g/dl per wk and the risk for cardiovascular and thromboembolic …

Hematocrit Level as a Marker of Outcome in ST-Segment Elevation Myocardial Infarction

Anemia is a well-known predictor of a poor outcome in patients with ST-segment elevation myocardial infarction (STEMI). In contrast, data relating erythrocytosis to clinical outcomes in patients with STEMI are limited. Because erythrocytosis predisposes to a prothrombotic state, we hypothesized it would be associated with an increased risk of thrombotic complications in patients with STEMI undergoing primary percutaneous coronary intervention. We studied 1,042 consecutive patients with STEMI who underwent primary percutaneous coronary intervention and were a part of our primary percutaneous coronary intervention registry from 2001 to 2007. Patients with cardiogenic shock and late arrival were excluded. Patients were allocated into 3 groups according to their baseline hematocrit: anemia (<36% for women and <39% for men), normal, erythrocytosis (>46% for women and >47% for men). The clinical outcomes were assessed at 1, 6, and 12 months. The patients with anemia had the greatest clinical risk profile. Patients with erythrocytosis had a lower risk profile than the other 2 groups, except for greater rates of smoking. The mortality rates were greatest among the patients with anemia, followed by the patients with erythrocytosis, who in turn had greater short-term mortality than patients with normal hematocrit. Multivariate analysis, which included patients with erythrocytosis and those with normal hematocrit (excluding the patients with anemia), revealed that erythrocytosis was associated with an odds ratio of 4.3 (95% confidence interval 1.4 to 13, p = 0.01) for 1-month mortality. In conclusion, although not as strong a predictor of mortality as anemia, erythrocytosis might be associated with increased short-term mortality compared to a normal hematocrit. The measurement of hematocrit can be used as a useful prognostic marker in patients with STEMI.

A blood transfusion leading to misdiagnosis of beta-thalassaemia carrier status.

Thalassaemia is the leading genetic problem in the Thai population, with the prevalence of the carrier state being as high as 30–40%1,2. Carriers live a normal life and can not be discriminated from the normal population unless blood investigations are performed. The diagnosis of a beta-thalassaemia carrier in thalassaemia screening and control programmes depends on the person’s percentage of haemoglobin (Hb) A23,4. The percentage of HbA2 in normal adults ranges between 2.5 to 3.5%5,6. To be diagnosed a beta-thalassaemia carrier, this value has to be higher than normal. Most institutes use a HbA2 cut-off level of 3.5%3–5. The cause of the increase in HbA2 in beta-thalassaemia carriers appears to involve both transcriptional and post-translational modifications of Hb synthesis6. Because a genetic diagnosis is not feasible in mass screening programmes, the percentage of HbA2 is a critical surrogate for the diagnosis of beta-thalassaemia carriers. Given the high prevalence of the carrier state in the Thai population, there is a chance of blood donation from thalassaemia carriers even with stringent blood bank criteria for donor selection. Here we report the interesting case of a patient misdiagnosed as a beta-thalassaemia carrier (elevated HbA2) after having received a blood transfusion. The patient had chronic anaemia from renal insufficiency. She was treated with an erythropoiesis-stimulating agent and occasional packed red cell (PRC) transfusions. A previous Hb analysis appeared to be normal (HbA2 2.9%). Thereafter, the Hb analysis was repeated by accident and the woman was indicated to be a beta-thalassaemia carrier with a HbA2 of 6.0%. However, subsequent beta-globin DNA sequencing did not reveal any beta gene mutations. The patient had been transfused one unit of PRC almost 2 months prior to the finding of elevated HbA2. Her blood donor was, therefore, traced back from the blood bank donor registry. A sample of blood product from this donor, which had been kept by routine in the blood bank, was rechecked with analysis of Hb. This donor appeared to be a HbE carrier. We retrospectively reconsidered how transfused HbE led to a misdiagnosis of beta-thalassaemia carrier status. The issue involved in this patient was the misinterpretation of transfused HbE as high HbA2 in the Hb analysis. Electrophoretic and chromatographic separation methods rely on differences in charges to resolve proteins from one another. HbA2 and HbE have similar charge differences. Electrophoretic and conventional methods of column chromatography are, therefore, incapable of separating HbA2 from HbE. High performance liquid chromatography (HPLC) with a cation exchange column produces good resolution of HbA2 from a group of positively charged Hb with similar charge differences such as HbS and HbC6. However, HbA2 and HbE are generally eluted from HPLC with the same retention time although in different amounts. The percentage of HbE in a HbE carrier is usually 28–30%7. The level of HbA2 in a beta-thalassaemia carrier is above 3.5% but generally does not exceed 8%5. When the amount of HbA2 from HPLC exceeds 8–10%, the Hb must be assumed to be HbE. The apparently high HbA2 in our case was actually transfused HbE but with a dilutional effect. One unit of PRC contains approximately 300 mL of red blood cell (RBC). Given that 30% of the Hb of a HbE carrier is HbE, one unit of PRC from a HbE carrier contains roughly 90 mL of HbE. Our patient, weighing approximately 60 kg, has an estimated blood volume of 4,200 mL (7% of body weight)8 and RBC volume of 840 mL (pretransfusion haematocrit 20%). Therefore, after transfusion of one unit of PRC, she would have approximately 90 mL of HbE out of 1,140 mL RBC (840 mL + 300 mL) which is 7–8%. This percentage is reasonably close to the percentage of “HbA2” found by Hb analysis after blood transfusion. Once the mystery had been solved, we had the chance to collect the patient’s blood for repeat Hb analysis almost 3 months after the transfusion of PRC from the HbE carrier. This third specimen still revealed an elevated HbA2 (7.0%), confirming the results in the second specimen collected. Another 5 months later, her HbA2 had returned to a normal level (3.0%) as expected. A similar situation may happen in an everyday-life scenario in Thailand without detection. Without performing Hb analysis, a HbE carrier donor can not be discriminated clinically from a normal donor even with stringent blood bank selection criteria. Most HbE carriers have normal Hb and haematocrit levels. Furthermore, some HbE carriers can have a normal mean corpuscular volume. Given the high prevalence of HbE carriers in Thailand, misdiagnosis of beta thalassaemia carriers may not be uncommon in Thai blood transfusion recipients.

Physiological Levels of Jak2 V617F Result in Enhanced Megakaryocyte Differentiation, Proplatelet Formation and Platelet Reactivity.

Abstract 226The major clinical challenge in treating patients with myeloproliferative diseases (MPD) such as essential thrombocythaemia (ET) and polycythaemia vera (PV) is to prevent thrombotic events. Despite adequate red cell and platelet count control by means of venesection or cytoreductive therapy and the use of anti-platelet agents, patients with ET and PV have a three-fold risk-increase of cardiovascular and cerebral ischaemic events. A V617F mutation in the Janus kinase 2 (Jak2) that causes constitutive activation of Jak2 has been shown to be present in >90% and ∼50% of PV and ET patients, respectively. The effect of this activation on the biology of primary megakaryocytic cells is not known and neither is it clear whether the thrombotic risk conferred by this mutation reflects the increase in red cell/platelet counts, an intrinsic increase in platelet reactivity or both. Studies in humans are hampered by the co-existence of normal and clonal haematopoiesis with significant clonal and phenotypic heterogeneity between patients. Chimaeric mouse models based on retroviral transduction of Jak2 V617F have marked overexpression of the mutant Jak2 and show a PV phenotype with normal platelet counts. Recently, Jak2 V617F transgenic mice models have been published but the transgenes have multiple (and variable) insertions and are therefore subject to position effects with varying degrees of expression of the mutant Jak2 compared to the wild-type allele. We have generated a Cre-inducible mouse model where the human Jak2 V617F gene has been knocked into one allele of the mouse endogenous Jak2 gene. Upon Cre induction, the mice exhibit an ET phenotype (platelet count increased by approximately 30% but with a normal haematocrit) that is stable for over 26 weeks. Bone marrow histology shows classical features of ET with increased numbers of megakaryocytes (MKs) and clusters with no fibrosis. Quantitative RT-PCR shows stable expression of Jak2 V617F in the MKs at a similar level to that of endogenous mouse Jak2 therefore reflecting the physiological situation found in human ET patients. In liquid cultures, bone marrow-derived MKs show increased ploidy in response to suboptimal concentrations of thrombopoietin (TPO) in keeping with the increased number of MKs found in the bone marrow histology. Crucially, in vitro proplatelet formation in mutant MKs was increased two-fold compared to MKs derived from litter-match control animals showing that platelet production may not only relate to the increased number of MKs but to intrinsic differences in MK biology and platelet production. Platelet aggregation studies and P-selectin expression in response to an array of agonists was not significantly different between mutant and controls but in vitro laminar flow assays show increased thrombus formation on collagen. Although Jak2V617F expression was down-regulated at protein level in mature MKs and platelets, analysis of downstream signalling pathways showed alteration of the phosphorylation status of Src kinases. This mouse model therefore provides a unique opportunity to understand the biological mechanism of increased platelet production and thrombotic risk in ET patients as well as unravelling the signalling pathways downstream of the Jak2 V617F in primary cells, which will be crucial in the context of specific therapeutic Jak2 inhibitors currently in clinical development.This work was supported by the British Heart Foundation Disclosures:No relevant conflicts of interest to declare.

Normal Serum-Erythropoietin (S-epo) Level at Diagnosis of Polycythemia Vera (PV) Correlates with LowJAK2V617F Mutant Allele Burden and Indicates Mild Phenotype.

Abstract 4978A low serum-erythropoietin (S-epo) level is a minor criterion of the World Health Organization (WHO) recommendations for diagnosing polycythemia vera (PV) even though previous studies indicate that a normal level does not always rule out PV. We wished to determine whether a normal S-epo level correlates with a low JAK2V617F mutant allele burden and a low phlebotomy (PHL) rate, since the relationship between S-epo level, JAK2V617F allele burden, and PHL rate heretofore has not been reported.At diagnosis, we grouped the S-epo levels of 26 PV patients (pts) as follows: low (<5 U/l), normal (5-10 U/l), and high (>10 U/l). Of the 26 pts, 4 (15.4%) had normal S-epo levels, and 22 had low S-epo levels. The diagnosis of PV in pts with normal S-epo levels was made by quantitative JAK2V617F analysis and elevated Cr51 red cell mass (RCM). All pts had a bone marrow biopsy consistent with PV.We determined the number of phlebotomies required to maintain normal hematocrit (hct) levels ('42% women, '45% men) as an assessment of disease severity during the period prior to myelosuppressive therapy. We then examined the number of phlebotomies per year (PHL/yr) in relation to S-epo level at diagnosis. Of the 26 pts, 14 were treated with PHL-only for a mean of 15 months (mos) prior to beginning other therapies including anagrelide, hydroxyurea, imatinib, and rIFNa-2b. The number of PHL/yr were grouped into 4 categories: 0 (none), 1 – 5 (low), 6 – 10 (moderate), and >10 (high). Of the 14 pts, 3 had a normal S-epo level at diagnosis, all of whom had a low PHL requirement, median 3/yr. The other 11 pts had low S-epo levels at diagnosis and a median PHL requirement of 6/yr (7 moderate and 4 low). Thus, while a low S-epo level at presentation was usually associated with moderate PHL requirement, a normal S-epo level at diagnosis was always associated with a subsequently low PHL requirement during the period of observation (mean 15 mos).Of the 26 pts, 14 had quantitative JAK2 analyses done at diagnosis. The other 12 were diagnosed prior to 2002 and quantitative JAK2 determinations were not available. Of the 14 pts, 2 had a normal S-epo level and a low JAK2V617F mutant allele burden (1-25%). These 2 pts also had a low PHL requirement. Thus, these pts who had normal S-epo levels, had JAK2V617F allele burdens in the lowest quartile, and had low PHL rates. Of the remaining 12 pts, 5 had JAK2V617F allele burdens in the 2nd (25-50%) quartile, 5 in the 3rd (50-75%) quartile, and 1 each in the 1st and 4th quartiles.We conclude (1) as previously reported, about 15% of pts with PV present with normal S-epo levels at diagnosis, suggesting a limitation of this WHO criterion, and (2) those pts with a low JAK2V617F allele burden and a normal S-epo level required fewer PHL/yr, all suggesting a more benign phenotype. This may provide a useful prognostic tool for patients with PV. DisclosuresNo relevant conflicts of interest to declare.

Recent Developments in Acute Pancreatitis

The incidence of acute pancreatitis (AP) has been increasing worldwide, but the major etiologies remain gallstones and alcohol. Several studies have reported that smoking is an independent risk factor for developing AP. Classification of AP has traditionally used the categories of mild and severe disease. However, a new intermediate category of moderately severe AP has been described with intermediate characteristics including a high incidence of local complications but a low mortality. Assessment criteria that can serve as early predictors of AP severity are often complex and not sufficiently accurate. However, several recently described criteria that rely on criteria such as the body mass index, physical findings, and simple laboratory measurements could prove useful if validated in large prospective studies. Many issues related to the therapy of AP are still unresolved. Although preliminary studies support the importance of early volume expansion for the treatment of acute pancreatitis, optimization of the amount and type of fluids will require further studies. Similarly, preliminary studies suggest that enteral nutrition might benefit patients with AP and could even be useful early in the course of disease. However, the timing and type of fluids as well as the intestinal infusion site require further study. Finally, issues related to the prophylactic use of antibiotics in patients with severe AP have not been resolved. While the process of clinical investigation moves slowly, progress has been made in clinical studies of AP.

What do Cardiovascular Nurses Know about the Hematological Management of Patients with Eisenmenger Syndrome?

We investigated the level of knowledge of hematological management of patients with Eisenmenger syndrome among general cardiovascular nurses and nurses who specialize in congenital heart disease (CHD). We conducted a survey at two international conferences attended by cardiovascular nurses. Nurses were asked to complete a questionnaire comprising two questions and three clinical case scenarios. Overall, 89 nurses participated (response rate 90.8%), 43 of whom specialized in CHD. The level of knowledge displayed among cardiovascular nurses is poor. About one-third of nurses not specialized in CHD recognized the definition of Eisenmenger syndrome and knew what normal hematocrit levels are. With respect to the cases presented, less than 10% of the nurses could give a correct answer. The level of knowledge of specialized nurses was significantly higher, but also here, important gaps in the level of knowledge could be observed. Less than two-thirds knew the reference values of hematocrit and knew the appropriate management in two cases. Less than half of the specialized nurses knew about the procedure of isovolumic phlebotomy. The level of knowledge displayed by cardiovascular nurses regarding the hematological management of patients with Eisenmenger syndrome is poor. Also the knowledge of nurses specialized in CHD could be improved.

Influence of laser-supported liposuction on hemoglobin, hematocrit, and erythrocyte values in patient's blood

Liposuction has been used as a surgical method of shaping the body for more than 30 years. Although of considerable interest, there are very few studies dealing with preoperative and postoperative blood parameters. There are no papers reporting what goes on in a patient's blood after laser-assisted lipectomy. Standard blood samples were evaluated in patients before and after lipectomy. We compared values of hemoglobin, erythrocytes, hematocrit, and leukocytes. We performed the same evaluation in patients undergoing laser-supported lipectomy. Moreover, we compared the decrease in postoperative values in laser-aided lipectomy patients with the reduction of values in conventional lipectomy patients. A paired two-sided Student's t test was used for statistical evaluation. p < 0.005 was acknowledged to be statistically significant. We found that hemoglobin, erythrocyte, and hematocrit levels after surgery were lower and differed specifically from the values before surgery. Nevertheless, no patient had values diverging from the norm after surgery. This was the case in both conventional and laser-aided surgery patients. We found no statistically significant difference when comparing the degrees of value decrease (“before minus after conventional” versus “before minus after laser-assisted”). Furthermore, we found that leukocyte levels increase very rapidly in venous blood within the 24 h following surgery. This is statistically significant in the case of both conventional and laser-assisted liposuction. This emphasizes that every patient has normal red blood cells, hemoglobin, and hematocrit levels after surgery. We conclude that conventional liposuction and laser-assisted lipectomy have a similar influence on hemoglobin erythrocytes and hematocrit. Our work is the first study of blood examinations during postoperative care following laser-assisted liposuction.

Special Article: The Normal Hematocrit Cardiac Trial Revisited

The Normal Hematocrit Cardiac Trial (NHCT) was the first large, randomized study of patients receiving hemodialysis to examine the outcomes of treating anemia to a target hematocrit range of 42 +/- 3% versus maintaining partial correction in a range of 30 +/- 3%. The results of the NHCT and a meta-analysis adding eight subsequent trials of normalization of hematocrit/hemoglobin in chronic kidney disease (CKD) have demonstrated increased thrombovascular events and mortality associated with the higher targets. This article expands and clarifies the results of the NHCT, including data that were edited from the original publication, and highlights findings from more recent studies in the field. Paradoxically, none of the randomized trials has reported an association between higher attained hemoglobin concentration and mortality within randomized groups. Mean platelet count did not increase among the patients in the normal-hematocrit group in the NHCT or in two other large trials, CREATE and CHOIR. Exposure to high doses of erythropoietic stimulating agents and/or intravenous iron could be mediating complications in the CKD anemia-normalization studies, but post-hoc analyses to probe such potential associations have yielded conflicting results and are clearly hindered by the risk of confounding by indication. The mechanisms underlying the deleterious outcomes associated with efforts to correct renal anemia fully remain unproven.

Infection by Trypanosoma vivax in goats and sheep in the Brazilian semiarid region: From acute disease outbreak to chronic cryptic infection

A study was undertaken to investigate the role of Trypanosoma vivax in sheep and goat mortality and abortions in the Brazilian semiarid region, where outbreaks had been previously reported in bovines. For this purpose, 177 goats and 248 sheep (20% of herds) were randomly sampled on four farms in the State of Paraiba in May and October 2008. The animals were screened for trypanosomes by the buffy coat technique (BCT) and PCR. Infected animals, ∼25% in both surveys, manifested apathy, pale mucous membranes, enlarged lymph nodes, weakness, weight loss, opacity of the cornea, blindness and abortion. However, the animals with acute and severe disease showing the highest levels of parasitemia and fever, which many times resulted in death, were only detected in the first survey. These severely diseased animals exhibited progressive weight loss and had the smallest packed cell volume (PCV) values. During survey 2, done in October 2008 on the same farms, only animals with low parasitemia and normal temperatures, PCV values and body weights were detected. Therefore, animals that spontaneously recovered from acute infection developed chronic and asymptomatic disease. This finding demonstrated for the first time that sheep and goats, which are the most important livestock in the semiarid region of Brazil, may be severely injured by T. vivax infection and also play a role as asymptomatic carriers and important sources of T. vivax to ruminants in general.

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Resolved

First Hematological Signals of Latent Anemia to Aging Population

Anemia is an independent risk factor for morbidity and mortality in an array of disorders common to seniors including cancer, renal diseases and heart diseases. The aim of this study was to identify the first hematological signals of latent anemia to aging population using as screening the hematological aspects of cells from peripheral blood and additional tests, establishing the etiology of anemia in the elderly.Method: Additional to level of hemoglobin(HGB) and hematocrit (HCT) have been included Hematological Indexes( MCV, HCV, MCHC ), red cell distribution width,(RDW), reticulocyte count (RET), serum iron (SI), total iron binding capacity,(TIBC), transferrin saturation index, (TSI), serum ferritin( SF), on an study of 140 adult hospitalized patients, in wars with chronic diseases males and females with ages past 65 years. Anemia of chronic diseases (ACD) is more common in the elderly than other group.In ACD correlation of hematological testes was following: 32 % with normal HGB, HCT and normal hematological indexes, 21.5 % with only MCV or HCV decreased, 22.5 % patients with HB in value 10.8 g/dl for women and 11.08 g/dl form men, 15 % patients with HB 9.8-10.6g/d L and 9% patients with HB 7.8-9.6, g/d L (mean SD=2,2 ); average number of Reticulocytes =1.2%; Corrected Index Ret = 0.6%; Production Index Reticulocytes, (PIR) = 1.4, meaning the hypo-regenerative anemia with globular value, GV =1.2. Precision: CV < 2% for RBC, CV < 1% for HB and CV < 2% for HCT. Accuracy: R > 0.95 for RBC, HGB and HCT. In this study was observed a higher prevalence of anemia in elderly men than in women. Anemia of renal disease is considered to be a distinct form of anemia and is typical due to decreased EPO production in 20 percent from normal value to adult persons. Discussion: Elderly anemic patients fail to show increases in erythrocytes progenitors and reticuloculocytes as a result of chronic stress along life. In some cases, the presence of anemia may reflect an underling or undetected medical condition. Most anemic adults are asymptomatic until HGB fall below normal values. For this reason a routine anemia screening should be recommended by HB, HCT and MCV, HCV, MCHC to persons with age past >_65 year.

First Hematological Signals of Latent Anemia to Aging Population

AbstractAnemia is an independent risk factor for morbidity and mortality in an array of disorders common to seniors including cancer, renal diseases and heart diseases. The aim of this study was to identify the first hematological signals of latent anemia to aging population using as screening the hematological aspects of cells from peripheral blood and additional tests, establishing the etiology of anemia in the elderly.Method: Additional to level of hemoglobin(HGB) and hematocrit (HCT) have been included Hematological Indexes( MCV, HCV, MCHC ), red cell distribution width,(RDW), reticulocyte count (RET), serum iron (SI), total iron binding capacity,(TIBC), transferrin saturation index, (TSI), serum ferritin( SF), on an study of 140 adult hospitalized patients, in wars with chronic diseases males and females with ages past 65 years. Results: Anemia of chronic diseases (ACD) is more common in the elderly than other group.In ACD correlation of hematological testes was following: 32 % with normal HGB, HCT and normal hematological indexes, 21.5 % with only MCV or HCV decreased, 22.5 % patients with HB in value 10.8 g/dl for women and 11.08 g/dl form men, 15 % patients with HB 9.8-10.6g/d L and 9% patients with HB 7.8-9.6, g/d L (mean SD=2,2 ); average number of Reticulocytes =1.2%; Corrected Index Ret = 0.6%; Production Index Reticulocytes, (PIR) = 1.4, meaning the hypo-regenerative anemia with globular value, GV =1.2. Precision: CV &lt; 2% for RBC, CV &lt; 1% for HB and CV &lt; 2% for HCT. Accuracy: R &gt; 0.95 for RBC, HGB and HCT. In this study was observed a higher prevalence of anemia in elderly men than in women. Anemia of renal disease is considered to be a distinct form of anemia and is typical due to decreased EPO production in 20 percent from normal value to adult persons. Discussion: Elderly anemic patients fail to show increases in erythrocytes progenitors and reticuloculocytes as a result of chronic stress along life. In some cases, the presence of anemia may reflect an underling or undetected medical condition. Conclusions: Most anemic adults are asymptomatic until HGB fall below normal values. For this reason a routine anemia screening should be recommended by HB, HCT and MCV, HCV, MCHC to persons with age past &gt;_65 year.

Response

Thank you for your letter regarding our article, “Differences in Glucose Values From Point-of-Care Glucose Meters and Laboratory Analysis in Critically Ill Patients.”1Our selection, a priori, of glucose differences of more than 20 mg/dL as being significant was based on a clinical judgment. It was not tied to an industry standard related to use of a point-of-care (POC) device for trend monitoring of glucose. Glucose determinations in critically ill patients are used for titration of continuous intravenous insulin infusions based on narrowly defined ranges of glucose values, necessitating a performance level that is more precise than what may be acceptable for trend monitoring.We agree that the POC device used in this study did perform as described in the manufacturer’s information. The concern we raised based on the results of this study, as well as those raised by other recent publications,2–4 is related to whether devices with this level of precision are appropriate when used for therapeutic insulin manipulations, not trend monitoring, in critically ill patients.This study was designed to determine the difference in POC and laboratory glucose values under circumstances of usual device usage (multiple device users, venous and capillary blood sources, in patients with normal and low hematocrit [HCT] levels), including typical laboratory turnaround times. Whereas the rate of glucose degradation prior to laboratory determination varies, most laboratories estimate this glucose decrease to be less than 7 mg/dL per hour. Because time from blood sampling to laboratory analysis for stat specimens is less than 30 to 40 minutes, this “delay” represents a small potential change in glucose (3–5 mg/dL). Although national laboratory standards groups may recommend no more than a 5-minute delay, most clinical laboratories in acute care hospitals do not or cannot process samples that rapidly.Data from this study concur with the concerns voiced in other studies2–4 of using POC glucose devices in patients with HCT values below the labeled lower limit (depending on the manufacturer, HCT less than 30% to 35%). Unfortunately, most clinical facilities do not restrict the use of these devices in patients with abnormally low HCT values, a clinical situation that is present in many hospitalized patients. Data from this clinical study emphasize the need to restrict use of POC devices to individuals with relatively normal HCT levels.

Late onset hypogonadism: an alternate cause for night sweats in the haematology clinic

Late onset hypogonadism: an alternate cause for night sweats in the haematology clinic

Bidirectional Glenn with Existing Transvenous Cardioverter-Defibrillator Leads

The population of patients with adult congenital heart disease is increasing. A significant number of these patients already have or will require placement of either a transvenous pacemaker or implantable cardioverter defibrillator. In addition to this, some with right ventricular dysfunction might benefit from volume unloading of the right ventricle by the construction of a superior cavopulmonary anastomosis. The usual technique for the bidirectional Glenn anastomosis precludes the presence of upper extremity transvenous hardware. We present a modified technique for the superior cavopulmonary anastomosis when pacing or cardioverter defibrillator leads are present.