ISRN Hematology

Hematological and Genetic Predictors of Daytime Hemoglobin Saturation in Tanzanian Children with and without Sickle Cell Anemia

Wed, 03 Apr 2013 08:59:10 +0000

Low hemoglobin oxygen saturation (SpO2) is common in Sickle Cell Anemia (SCA) and associated with complications including stroke, although determinants remain unknown. We investigated potential hematological, genetic, and nutritional predictors of daytime SpO2 in Tanzanian children with SCA and compared them with non-SCA controls. Steady-state resting pulse oximetry, full blood count, transferrin saturation, and clinical chemistry were measured. Median daytime SpO2 was 97% (IQ range 94–99%) in SCA (N = 458), lower () than non-SCA (median 99%, IQ range 98–100%; N = 394). Within SCA, associations with SpO2 were observed for hematological variables, transferrin saturation, body-mass-index z-score, hemoglobin F (HbF%), genotypes, and hemolytic markers; mean cell hemoglobin (MCH) explained most variability (, Adj ). In non-SCA only age correlated with SpO2. -thalassemia 3.7 deletion highly correlated with decreased MCH (Pearson correlation coefficient 0.60, ). In multivariable models, lower SpO2 correlated with higher MCH (-coefficient 0.32, ) or with decreased copies of -thalassemia 3.7 deletion (-coefficient 1.1, ), and independently in both models with lower HbF% (-coefficient 0.15, ) and Glucose-6-Phosphate Dehydrogenase genotype (-coefficient 1.12, ). This study provides evidence to support the hypothesis that effects on red cell rheology are important in determining SpO2 in children with SCA. Potential mechanisms and implications are discussed.

Assessment of Hepatic and Pancreatic Iron Overload in Pediatric Beta-Thalassemic Major Patients by Weighted Gradient Echo Magnetic Resonance Imaging

Thu, 28 Mar 2013 08:05:57 +0000

Background. MRI has emerged for the noninvasive assessment of iron overload in various tissues. The aim of this paper is to evaluate hepatic and pancreatic iron overload by weighted gradient echo MRI in young beta-thalassemia major patients and to correlate it with glucose disturbance and postsplenectomy status. Subjects and Methods. 50 thalassemic patients, in addition to 15 healthy controls. All patients underwent clinical assessment and laboratory investigations. Out of 50 thalassemic patients, 37 patients were splenectomized. MRI was performed for all subjects. Results. All patients showed significant reduction in the signal intensity of the liver and the pancreas on GRD compared to controls, thalassemic patients who had abnormal glucose tolerance; diabetic and impaired glucose tolerance patients displayed a higher degree of pancreatic and hepatic siderosis and more drop in their signal intensity than those with normal blood sugar level. Splenectomized thalassemic patients had significantly lower signal intensity of the liver and pancreas compared to nonsplenectomized patients. Conclusion. gradient echo MRI is noninvasive highly sensitive method in assessing hepatic and pancreatic iron overload in thalassemic patients, more evident in patients with abnormal glucose tolerance, and is accelerated in thalassemic splenectomized patients.

Hemoglobin A2 Lowered by Iron Deficiency and α-Thalassemia: Should Screening Recommendation for β-Thalassemia Change?

Tue, 12 Mar 2013 14:23:03 +0000

Screening for β-thalassemia trait (BTT) relies on measuring hemoglobin (Hb) A2. Since multiple factors can affect HbA2 levels, the screening can become unreliable. In 1356 healthy Arabs enrolled into a federally funded premarital BTT screening program, the effects of iron deficiency (ID), -thalassemia trait, gender, smoking, and tribalism on HbA2 were studied. The complete blood count and hemoglobin fractions were determined on the entire cohort; serum ferritin (<15 μg/L) in 391 subjects was used to determine ID. BTT was present in 29 (2.1%) subjects (HbA2 > 3.5%). Among 77(20.3%) subjects with ID, the mean HbA2 (%) was 0.2% lower than in subjects without iron deficiency (%, ). In 65 (38%)/172 subjects with phenotypic -thalassemia trait, the mean HbA2 (%) was 0.13% lower than in subjects without -thalassemia trait, . The mean HbA2 did not differ between males and females, smokers and nonsmokers, and between the tribes. Thus, 35 (2.6%) subjects with HbA2 between 3.2 and 3.5% were at a risk of false negative diagnosis of BTT. Since iron deficiency and -thalassemia are both common and both lower HbA2, modifications in screening recommendations for BTT are proposed.

MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies

Ronit Vogt Sionov — Tue, 29 Jan 2013 09:39:03 +0000

The initial response of lymphoid malignancies to glucocorticoids (GCs) is a critical parameter predicting successful treatment. Although being known as a strong inducer of apoptosis in lymphoid cells for almost a century, the signaling pathways regulating the susceptibility of the cells to GCs are only partly revealed. There is still a need to develop clinical tests that can predict the outcome of GC therapy. In this paper, I discuss important parameters modulating the pro-apoptotic effects of GCs, with a specific emphasis on the microRNA world comprised of small players with big impacts. The journey through the multifaceted complexity of GC-induced apoptosis brings forth explanations for the differential treatment response and raises potential strategies for overcoming drug resistance.

CD47: A Cell Surface Glycoprotein Which Regulates Multiple Functions of Hematopoietic Cells in Health and Disease

Per-Arne Oldenborg — Mon, 21 Jan 2013 15:52:08 +0000

Interactions between cells and their surroundings are important for proper function and homeostasis in a multicellular organism. These interactions can either be established between the cells and molecules in their extracellular milieu, but also involve interactions between cells. In all these situations, proteins in the plasma membranes are critically involved to relay information obtained from the exterior of the cell. The cell surface glycoprotein CD47 (integrin-associated protein (IAP)) was first identified as an important regulator of integrin function, but later also was shown to function in ways that do not necessarily involve integrins. Ligation of CD47 can induce intracellular signaling resulting in cell activation or cell death depending on the exact context. By binding to another cell surface glycoprotein, signal regulatory protein alpha (SIRPα), CD47 can regulate the function of cells in the monocyte/macrophage lineage. In this spotlight paper, several functions of CD47 will be reviewed, although some functions may be more briefly mentioned. Focus will be on the ways CD47 regulates hematopoietic cells and functions such as CD47 signaling, induction of apoptosis, and regulation of phagocytosis or cell-cell fusion.

Comparative Effects of Three Iron Chelation Therapies on the Quality of Life of Greek Patients with Homozygous Transfusion-Dependent Beta-Thalassemia

Vasilis Goulas, Alexandra Kourakli-Symeonidis, and Charalambos Camoutsis — Mon, 17 Dec 2012 18:12:58 +0000

This prospective study assessed the quality of life of patients with homozygous transfusion-dependent beta-thalassemia in Greece receiving three different iron chelation treatments. Patients enrolled were receiving one of the following chelation therapies: deferoxamine (), deferasirox (), or deferoxamine in combination with deferiprone (). The three groups were compared in terms of their quality of life, satisfaction and adherence to treatment, control of their health, and self-esteem through the completion of five questionnaires. A higher percentage of patients receiving deferoxamine felt that their treatment negatively influenced their body and skin appearance and limited their ability to work, attend school, and perform daily tasks (). The adherence to treatment rate and self-esteem were the lowest in the deferoxamine group (). The deferoxamine group also had the lowest physical component summary score in the SF-36 questionnaire (). This study suggests that the quality of life of beta-thalassemia patients receiving chelation therapy is dependent on the type of iron chelation treatment they receive. The study provides insight into important factors associated with the quality of life of these patients, which are essential for developing a more suitable clinical support team and counseling in order to maximize the treatment benefits for these patients in daily clinical practice.

Transfusion Practices in the Management of Sickle Cell Disease: A Survey of Florida Hematologists/Oncologists

Wed, 12 Dec 2012 15:59:33 +0000

The purpose of this study was to characterize transfusion practices in the management of sickle cell disease and to identify factors attributing to differences in prescribing practices among Florida hematologists/oncologists. A cross-sectional study was performed in 2005-2006 utilizing a mail survey. The survey instrument addressed practice characteristics, sickle cell patient populations, transfusion settings, indications and techniques, red blood cell phenotype specifications/modifications, use of practice guidelines, and educational resource utilization. One hundred fifty two physicians (75% adult-oriented, 25% pediatric) completed the survey. Non-academic practice settings (78 %) were the primary location. Pediatric practices had a larger percentage of patients with overt strokes, and receiving hydroxyurea therapy than adult-oriented practices. The majority of survey respondents did not request limited phenotypically matched red blood cells on a routine basis. The majority of pediatric practices (60%) had individually defined transfusion practice guidelines in contrast to 8% of adult-oriented practices. There were statistically significant differences for pediatric and adult-oriented practices in managing certain acute and chronic transfusion indications. Analysis of clinical vignette data revealed variation among hematologists/oncologists in the transfusion management of common clinical scenarios. The study underscores the need for the development and dissemination of comprehensive sickle cell transfusion guidelines and protocols.

RhC Phenotyping, Adsorption/Elution Test, and SSP-PCR: The Combined Test for D-Elute Phenotype Screening in Thai RhD-Negative Blood Donors

Wed, 14 Nov 2012 10:46:01 +0000

The Rhesus (Rh) blood group is the most polymorphic human blood group and it is clinically significant in transfusion medicine. Especially, D antigen is the most important and highly immunogenic antigen. Due to anti-D, it is the cause of the hemolytic disease of the newborn and transfusion reaction. About 0.1%–0.5% of Asian people are RhD-negative, whereas in the Thai population, the RhD-negative blood type only occurs in 0.3%. Approximately 10%–30% of RhD-negative in Eastern Asian people actually were D-elute (DEL) phenotype, the very weak D antigen that cannot be detected by indirect antiglobulin test (IAT). There are many reports about anti-D immunization in RhD-negative recipients through the transfusion of red blood cells from individuals with DEL phenotype. D-elute phenotype screening in Thai RhD-negative blood donors was studied to distinguish true RhD-negative from DEL phenotype. A total of 254 Thai serologically RhD-negative blood donors were tested for RhCE phenotypes and anti-D adsorption/elution test. In addition, RhC(+) samples were tested for RHD 1227A allele by SSP-PCR technique. The RhD-negative phenotype samples consisted of 131 ccee, 4 ccEe, 1 ccEE, 101 Ccee, 16 CCee, and 1 CcEe. The 42 Ccee and 8 CCee phenotype samples were typed as DEL phenotype and 96% of DEL samples were positive for RHD 1227A allele. The incidence of RhC(+) was 46.4%, and 48 of the 118 RhC(+) samples were positive for both anti-D adsorption/elution test and SSP-PCR technique for RHD 1227A allele. The sensitivity and specificity were 96% and 100%, respectively, for RHD 1227A detection as compared with the adsorption/elution test. In conclusion, RhC(+) phenotype can combine with anti-D adsorption/elution test and RHD 1227A allele SSP-PCR technique for distinguishing true RhD-negative from DEL phenotype.

Implications of Weight and Body Mass Index for Plasma Donation and Health

Wed, 14 Nov 2012 09:59:39 +0000

This study determined the percentage of potential plasma donors who could donate plasma in the 3 allowable plasma volume limit categories as specified by the Food and Drug Administration (FDA), as well as the association of the body mass index (BMI) of these individuals with age, blood pressure, oral temperature, and pulse. Of 315 plasma donors analyzed, 107 (34.0%) weighed between 110 and 149 lbs (50.0–67.7 kg), 89 (28.2%) weighed between 150 and174 lbs (68.2–79.1 kg), and 119 (37.8%) weighed >175 lbs (79.5 kg), theoretically allowing collection of an additional 101.4 liters (16% more plasma) from both heavier categories based on FDA standards for plasma donor quantities. BMI was positively associated with age, mean arterial pressure (MAP), and pulse (Pearson’s , 0.24, and 0.18, resp., values <0.05), but not with oral temperature. Average BMI for females was higher than for males (, ), and BMI for African Americans was higher than for White and Asian participants ( and , resp., s <0.05). A significant association was also found in the sex by race interaction with BMI (). Follow-up analyses suggested a significant difference in BMI by sex among African Americans, higher BMI among African American females than Asian and White males, and higher BMI among White females than African American males (s <0.05).

Evaluation of X-Chromosome Inactivation Patterns in Patients with Acute Myeloid Leukemia during Remission

Tue, 23 Oct 2012 08:56:04 +0000

The aim of this study was to evaluate the patterns of X-chromosome inactivation during the remission in acute myeloid leukemia (AML) at the RNA level. Two hundred normal females and 45 female patients with AML entered the study. The frequency of heterozygosity was 48.5% (119/245) for P55, 40% (93/245) for IDS, and only 28.9% (71/245) for G6PD. Some individuals were heterozygous for more than one gene polymorphism. Overall, one hundred normal individuals proved showed to be heterozygous for at least one of the above polymorphisms. 92/100 (92%) normal females showed a polyclonal pattern. Clonal patterns were observed in 44/45 (98%) AML patients at presentation. Of 27 patients who were followed after remission, 23 (85.2%) patients showed a clonal pattern. Ten patients were available for a longer followup (up to 12 months) and the clonal pattern was observed in seven patients. It can be concluded that clonality at remission is a frequent event in AML and does not necessarily mean relapse of the disease. There is also a possibility of conversion of clonality to polyclonality over time.

Evaluation of Transfusion Pyrexia: A Review of Differential Diagnosis and Management

Oladimeji P. Arewa — Mon, 15 Oct 2012 11:56:23 +0000

Background/purpose. Transfusion pyrexia (fever) is an important clinical sign/symptom occurring either as an isolated event or as part of a constellation of signs and symptoms in relation to blood transfusion. It is an important cause of morbidity and may be an important sign of life-threatening complications of blood transfusion. Pyrexia is often a reason for the discontinuation of a blood transfusion episode, and adequate evaluation remains a challenge for clinicians. The decision to stop a blood transfusion episode on account of fever is often a difficult one. This paper reviews the differential diagnosis of transfusion pyrexia (TP), the pathogenesis as well as current management measures. Study selection and data source. Literature sources include medical texts, journals, dissertations, and internet-based electronic materials Results and conclusion. Adequate evaluation of pyrexia accompanying blood transfusion remains a challenge for clinicians. An algorithm to assist the clinician in the evaluation of fever occurring in a blood transfusion recipient is developed and presented. Continuous medical education is necessary for clinicians towards improved patient care in transfusion medicine.

The Effects of Continuous Blood Purification for SIRS/MODS Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Wed, 26 Sep 2012 11:24:17 +0000

Background. Continuous veno-venous hemofiltration (CVVH) has aroused great concern in recent years because its effect on clearing inflammatory mediators and its mechanism of clinical effects in the treatment of critical illness has also become a research direction. Objective. To evaluate the efficacy of continuous blood purification for systemic inflammatory response syndrome (SIRS)/multiple organ dysfunction syndrome (MODS) patients. Methods. A systematic review of the literature was undertaken to assess randomized controlled trials on CVVH. Results. 11 RCTs involving a total of 414 patients were included. Compared with the control group, CVVH for SIRS/MODS patients has several advantages including better effects on clearing the plasma inflammatory mediators IL-6 [, 95%CI, (−0.83, −0.07), , 95%CI, (−1.52, −0.62)], on plasma TNF-alfa [, 95%CI, (−1.69, −0.04), , 95%CI, (−2.49, −0.35)], lower white blood cell (WBC) count [, 95%CI, (1.49, 3.73)], shorter hospital stays [ days, 95%CI, (−10.68, −3.74)] and better stability of hemodynamics. However, there is no significant difference in the mortality rate [MODS:, 95%CI, (0.38, 1.01), SIRS:, 95%CI, (0.57, 1.08)]. Conclusions. The study showed that CVVH was able to eliminate inflammatory mediators (TNF-alfa, IL-6) in plasma effectively, lower WBC count and shorter hospital stays than conventional therapeutic measures.

Need for Nucleic Acid Testing in Countries with High Prevalence of Transfusion-Transmitted Infections

Rohit Jain, Pankaj Aggarwal, and Gajendra Nath Gupta — Wed, 12 Sep 2012 14:58:13 +0000

Introduction. In India, family/replacement donors still provide more than 45% of the collected blood. With increasing voluntary blood donation and the still-prevalent infectious diseases in donors, we need to augment transfusion-transmitted infections (TTIs) testing before use. Our study was aimed to know the seroprevalence of TTIs among the donors of Rajasthan and the need for newer technologies like nucleic acid testing (NAT). Materials and Methods. Enhanced chemiluminescence immunoassay (ECi) was used for detection of HBsAg, anti-HIV, and anti-HCV in donor serum. 50% of the blood units which were negative on ECi were randomly selected and subjected to NAT testing for HBV, HCV, and HIV. Results. The total seroprevalence of TTIs is 2.62%. Of the randomly selected donor units negative by ECi, 8 turned out to be reactive on NAT testing: 4 were voluntary and 4 were family/replacement donors. Combined NAT yield (NAT reactive/seronegative) for HIV, HCV, and HBV was 0.034% (1 in 2972 donations). All the 8 reactive samples were positive for HBV DNA. Conclusion. In countries with a high prevalence of TTIs like India there are likely to be a significant number of window period donations that can be identified by NAT which may be implemented in blood centers allover India with serological testing to provide safe blood and cost alone should not be a deterrent to the government and implementing agencies.

The Platelet Function Analyzer (PFA-100) as a Screening Tool in Neurosurgery

Wed, 08 Aug 2012 10:27:37 +0000

We investigated whether the inclusion of the PFA-100 in the preoperative screening of neurosurgical patients might reduce perioperative bleeding complications. Patients with intracranial space-occupying lesions who were scheduled for neurosurgery underwent routine preoperative PFA-100 testing. In case of an abnormal PFA test, patients received prophylactic treatment with desmopressin. 93 consecutive patients were compared to 102 consecutive patients with comparable characteristics operated before introduction of the PFA-100 testing. 2 patients (2.2%) in the PFA group and 2 patients (2.0%) in the non-PFA group experienced clinically relevant intracranial bleeding confirmed by computed tomography (OR 1.05, 95% CI 0.39–2.82; 𝑃=1.0). Transfusions were not significantly different between the two groups. 13 (14.0%) patients in the PFA group and 5 (4.9%) patients in the non-PFA group received desmopressin (OR 3.2, 95% CI 1.1–9.2; 𝑃=0.045). Preoperative screening with the PFA-100 did result in a significant increase in the administration of desmopressin, which could not reduce perioperative bleeding complications or transfusions.

Intermittent Iron Folate Supplementation: Impact on Hematinic Status and Growth of School Girls

Aditi Sen and Shubhada Kanani — Thu, 26 Jul 2012 13:57:08 +0000

In view of high iron needs for adolescent growth, this paper studied the impact of daily vs. intermittent (once and twice weekly) iron folic acid (IFA) supplementation on hemoglobin levels and pubertal growth among primary school girls in early adolescence (9–13 years) of Vadodara, India. Methods. Hemoglobin (Hb), height and weight of the girls were assessed using standard methods. In three experimental schools (ES) IFA tablets in a dose of 100 mg Fe+0.5 mg folic acid was given either daily, once weekly or twice weekly for one year. The fourth school (control: CS) did not receive any intervention. Results. Hb levels significantly improved (𝑃<0.01) in all ES compared to CS. Body Mass Index (BMI) increment in ES vs CS was significant (𝑃<0.05) in twice weekly IFA and daily IFA. Within ES groups, mean Hb and BMI increments were comparable between twice weekly IFA and daily IFA. Anemic ES girls showed higher Hb and BMI increments vs. non-anemic girls. Better the Hb response, greater was the benefit on BMI. Conclusion: Twice-weekly IFA supplementation was comparable to daily IFA as regards impact on Hb and growth; at less cost and greater feasibility. Once-weekly dose was inadequate to significantly improve growth.

Thrombotic Microangiopathies

Mohamed Radhi and Shannon L. Carpenter — Wed, 25 Jul 2012 10:19:47 +0000

Thrombotic microangiopathy results from thrombotic occlusion of the microvasculature leading to fragmentation of red blood cells, profound thrombocytopenia, and a microangiopathic hemolytic anemia with elevation of lactate dehydrogenase and negative direct Coomb’s test. This constellation of clinical and laboratory findings is not due to one disease entity; rather, it represents a variety of underlying diagnoses. Among the major disease entities are TTP/HUS, which can be congenital or acquired, bacterial infections, medications, vascular or endothelial pathology like Kasabach-Merritt phenomenon, and stem cell transplantation. In this paper, we offer a review of some of the major causes of thrombotic microangiopathy.

K3EDTA Vacuum Tubes Validation for Routine Hematological Testing

Tue, 24 Jul 2012 10:46:54 +0000

Background and Objective. Some in vitro diagnostic devices (e.g, blood collection vacuum tubes and syringes for blood analyses) are not validated before the quality laboratory managers decide to start using or to change the brand. Frequently, the laboratory or hospital managers select the vacuum tubes for blood collection based on cost considerations or on relevance of a brand. The aim of this study was to validate two dry K3EDTA vacuum tubes of different brands for routine hematological testing. Methods. Blood specimens from 100 volunteers in two different K3EDTA vacuum tubes were collected by a single, expert phlebotomist. The routine hematological testing was done on Advia 2120i hematology system. The significance of the differences between samples was assessed by paired Student’s t-test after checking for normality. The level of statistical significance was set at 𝑃<0.05. Results and Conclusions. Different brand’s tubes evaluated can represent a clinically relevant source of variations only on mean platelet volume (MPV) and platelet distribution width (PDW). Basically, our validation will permit the laboratory or hospital managers to select the brand’s vacuum tubes validated according to him/her technical or economical reasons for routine hematological tests.

Cotransduction with MGMT and Ubiquitous or Erythroid-Specific GFP Lentiviruses Allows Enrichment of Dual-Positive Hematopoietic Progenitor Cells In Vivo

Thu, 19 Jul 2012 19:00:20 +0000

The P140K point mutant of MGMT allows robust hematopoietic stem cell (HSC) enrichment in vivo. Thus, dual-gene vectors that couple MGMT and therapeutic gene expression have allowed enrichment of gene-corrected HSCs in animal models. However, expression levels from dual-gene vectors are often reduced for one or both genes. Further, it may be desirable to express selection and therapeutic genes at distinct stages of cell differentiation. In this regard, we evaluated whether hematopoietic cells could be efficiently cotransduced using low MOIs of two separate single-gene lentiviruses, including MGMT for dual-positive cell enrichment. Cotransduction efficiencies were evaluated using a range of MGMT : GFP virus ratios, MOIs, and selection stringencies in vitro. Cotransduction was optimal when equal proportions of each virus were used, but low MGMT : GFP virus ratios resulted in the highest proportion of dual-positive cells after selection. This strategy was then evaluated in murine models for in vivo selection of HSCs cotransduced with a ubiquitous MGMT expression vector and an erythroid-specific GFP vector. Although the MGMT and GFP expression percentages were variable among engrafted recipients, drug selection enriched MGMT-positive leukocyte and GFP-positive erythroid cell populations. These data demonstrate cotransduction as a mean to rapidly enrich and evaluate therapeutic lentivectors in vivo.

Detection of Common Deletional Alpha-Thalassemia Spectrum by Molecular Technique in Kelantan, Northeastern Malaysia

Thu, 19 Jul 2012 08:25:31 +0000

Thalassemia is a hereditary blood disorder that results from genetic defects causing deficient synthesis of hemoglobin polypeptide chains. Although thalassemia mostly affects developing countries, there is limited knowledge of its accurate frequency and distribution in these regions. Knowing the prevalence of thalassemia and the frequency of responsible mutations is therefore an important step in the prevention and control program as well as treatment strategies. This study was performed to determine the prevalence and to study the spectrum of gene deletions that are responsible in α-thalassemia in Kelantan, located in northeastern Malaysia. A total 400 first-time blood donors from multiple areas of donation centre were chosen randomly. The presence of three types of α-thalassemia gene deletion in southeast Asian population which were -SEAdeletion, -α3.7 rightward deletion, and -α4.2 leftward deletion was detected by using multiplex PCR method. 37 (9.25%) of blood donors were confirmed to have α-thalassemia deletion types. 34 (8%) were heterozygous for α3.7 deletion, 1 (0.25%) was heterozygous for α4.2 deletion, and 2 (0.5%) were heterozygous for SEA type deletion. Alpha-thalassemia-2 with 3.7 deletion was the most common determinant detected in Kelantan Malay compared to other ethnic groups. It has been noted that alpha-thalassemia-2 with 3.7 deletion is the most common type of α-thalassemia throughout the world.

A Method for the In Vivo Measurement of Zebrafish Tissue Neutrophil Lifespan

Mon, 16 Jul 2012 09:03:58 +0000

Neutrophil function is thought to be regulated, in large part, by limitation of lifespan by apoptosis. A number of studies suggest that circulating neutrophils have a half-life of approximately 6 hours, although contradictory evidence exists. Measuring tissue neutrophil lifespan, however, is more problematic. It is thought that tissue neutrophils survive longer, perhaps with a half-life in the order of 3–5 days, but this has never been directly measured. Zebrafish are an emerging model organism, with several advantages for the study of vertebrate immunity. In zebrafish, neutrophils constitutively assume tissue locations allowing their direct study in vivo. Using a transgenic approach, neutrophils were labelled with a photoconvertible pigment, Kaede. Photoconversion parameters were optimised and the stability of the Kaede confirmed. Individual neutrophils were photoconverted by scanning a confocal 405 nm laser specifically over each cell and their survival monitored for 48 hours, revealing an in vivo half-life for zebrafish tissue neutrophils of around 120 hours (117.7 hrs, 95% CI 95.67–157.8). Laser energy did not extend neutrophil lifespan, and we conclude that this represents a lower bound for the lifespan of a resting tissue neutrophil in the developing zebrafish larva. This is the first direct measurement of the lifespan of an in vivo tissue neutrophil.

Hematological Manifestations of SLE at Initial Presentation: Is It Underestimated?

P. K. Sasidharan, M. Bindya, and K. G. Sajeeth Kumar — Mon, 09 Jul 2012 10:32:47 +0000

SLE can present with hematological manifestations alone or along with features of other system involvement. With a low index of clinical suspicion or inadequate follow up the diagnosis may be delayed or missed at the time of presentation, in those with hematological abnormalities as the initial manifestation. An observational study was conducted among patients of SLE, in a tertiary referral centre of North Kerala, with the purpose of estimating the proportion of patients with hematological manifestations as the initial presentation of the disease and to study their nature. It was observed that 82% of the patients had hematological manifestations at presentation. It is the most common presenting manifestation of SLE in people of North Kerala. Autoimmune hypothyroidism was one of the common coexisting abnormalities in these patients, which is not included in the American College of Rheumatology (ACR) criteria for diagnosis. Arthritis was uncommon among those who presented with hematological manifestations. A significant number of patients do not satisfy the ACR criteria at the time of diagnosis but do so on follow up. The ACR criteria are weak to diagnose such patients and therefore need revision. We therefore propose an alternative to ACR criteria as “Kozhikode criteria for SLE”.

Pattern of 𝜷-Thalassemia and Other Haemoglobinopathies: A Cross-Sectional Study in Bangladesh

Thu, 14 Jun 2012 14:01:20 +0000

Thalassemia and other structural haemoglobinopathies are the major erythrocyte formation disorder prevalent in certain parts of the world including Bangladesh. We investigated 600 cases of anaemic patients referred from various parts of the country for diagnosis and counselling during 3 months (April to June 2011) of time. The most common form of haemoglobin (Hb) formation disorder observed in 600 subjects studied was β-thalassemia minor (21.3%). Two other conditions, such as E-β-Thalassemia and HbE trait, were also fairly common (13.5 and 12.1%, resp.) in the total subjects studied. Other forms of haemoglobin formation disorders observed were HbE disease (9.2%), Hb D/S trait (0.7%), β-thalassemia major (0.5%), and δ-β-thalassemia (0.5%). The majority of the haemoglobinopathies belonged to neonatal to childhood period (0–15 years), followed by reproductive age group (16–45 years). Few old-age (46+ years) cases were also detected in course of clinical complications.

Angiogenesis in Non-Hodgkin's Lymphoma: An Intercategory Comparison of Microvessel Density

Tue, 27 Mar 2012 09:35:14 +0000

Background. This study was aimed at comparing angiogenesis, seen as microvessel density (MVD) in subtypes of non-Hodgkin’s lymphoma (NHL). Methods. In this study, 64 cases of NHL diagnosed over a three-year period were included along with 15 lymph node biopsies of reactive hyperplasia. NHLs were classified using REAL classification, and immunohistochemistry was performed for CD34 in all cases. CD34-stained sections were evaluated for “hot spots,” where MVD was assessed and expressed as per mm2. Appropriate statistical methods were applied. Results. There were 6 cases of well-differentiated lymphocytic lymphoma (SLL), 21 diffuse large B-cell lymphoma (DLBCL), 15 follicular lymphoma, 10 lymphoblastic lymphoma, 7 MALToma, and 5 peripheral T-cell lymphoma (PTCL). Mean MVD was highest in reactive hyperplasia (191.92±12.16 per mm2) compared to all NHLs. Among NHLs, PTCL demonstrated the highest MVD (183.42±8.24) followed by DLBCL (149.91±13.68). A significant difference was found in MVD between reactive and individual lymphoma groups. SLL had significantly lower MVD than other lymphoma subtypes. Conclusion. Angiogenesis, assessed by MVD, showed significant differences among subtypes of NHL, especially the indolent types like SLL. The higher MVD in aggressive lymphomas like PTCL and DLBCL can potentially be utilized in targeted therapy with antiangiogenic drugs.

Anemia in Heart Failure Patients

Michael G. Alexandrakis and George Tsirakis — Sun, 25 Mar 2012 13:41:28 +0000

Heart failure is a very common disease, with severe morbidity and mortality, and a frequent reason of hospitalization. Anemia and a concurrent renal impairment are two major risk factors contributing to the severity of the outcome and consist of the cardio renal anemia syndrome. Anemia in heart failure is complex and multifactorial. Hemodilution, absolute or functional iron deficiency, activation of the inflammatory cascade, and impaired erythropoietin production and activity are some pathophysiological mechanisms involved in anemia of the heart failure. Furthermore other concomitant causes of anemia, such as myelodysplastic syndrome and chemotherapy, may worsen the outcome. Based on the pathophysiology of cardiac anemia, there are several therapeutic options that may improve hemoglobin levels, tissues’ oxygenation, and probably the outcome. These include administration of iron, erythropoiesis-stimulating agents, and blood transfusions but still the evidence provided for their use remains limited.

Clinical and Electrocardiographic Evaluation of Sickle-Cell Anaemia Patients with Pulmonary Hypertension

Sun, 25 Mar 2012 11:44:06 +0000

Pulmonary hypertension is an emerging complication of sickle cell anaemia with associated increased risk of mortality. In order to evaluate the clinical and electrocardiographic findings in adult sickle-cell patients with pulmonary hypertension, a cross sectional study was conducted on sixty two sickle cell anaemia patients and sixty two age and sex matched normal controls. Elevated pulmonary artery pressures (PAP), defined by PAP ≥ 30 mm Hg on echocardiography, was demonstrated in 41.9% of patients with sickle cell anaemia and in 3.2% of the controls; 𝜒2=26.571, 𝑃<0.001. Right ventricular hypertrophy, increased P-wave duration, QTc interval, and QTc dispersion were significantly associated with pulmonary hypertension. Significant correlation was found between mean PAP and (1) Frequency of crisis (Spearman correlation = 0.320; 𝑃=0.011), (2) body mass index (Pearson’s correlation = −0.297; 𝑃=0.019), and (3) QTc interval (Pearson’s correlation 0.261; 𝑃=0.040). Pulmonary hypertension in adult sickle anaemia patients is associated with electrocardiographic evidence of right ventricular hypertrophy, and correlates significantly with frequency of vaso-occlusive crisis, and QTc interval. The observations by this study tend to suggest that these parameters could be useful for early detection and prevention of pulmonary hypertension in patients with sickle cell anaemia.

Sexual Dimorphism in Hematocrit Response Following Red Blood Cell Transfusion of Critically Ill Surgical Patients

Thu, 22 Mar 2012 15:11:38 +0000

The change in hematocrit (ΔHct) following packed red blood cell (pRBCs) transfusion is a clinically relevant measurement of transfusion efficacy that is influenced by post-transfusion hemolysis. Sexual dimorphism has been observed in critical illness and may be related to gender-specific differences in immune response. We investigated the relationship between both donor and recipient gender and ΔHct in an analysis of all pRBCs transfusions in our surgical intensive care unit (2006–2009). The relationship between both donor and recipient gender and ΔHct (% points) was assessed using both univariate and multivariable analysis. A total of 575 units of pRBCs were given to 342 patients; 289 (49.9%) donors were male. By univariate analysis, ΔHct was significantly greater for female as compared to male recipients (3.81% versus 2.82%, resp., 𝑃<0.01). No association was observed between donor gender and ΔHct, which was 3.02% following receipt of female blood versus 3.23% following receipt of male blood (𝑃=0.21). By multivariable analysis, recipient gender remained associated significantly with ΔHct (𝑃<0.01). In conclusion, recipient gender is independently associated with ΔHct following pRBCs transfusion. This association does not appear related to either demographic or anthropomorphic factors, raising the possibility of gender-related differences in recipient immune response to transfusion.

Mechanism of Protein-Z-Mediated Inhibition of Coagulation Factor Xa by Z-Protein-Dependent Inhibitor: A Molecular Dynamic Approach

Mohammad Reza Dayer, Omid Ghayour, and Mohammad Saaid Dayer — Tue, 20 Mar 2012 14:09:53 +0000

Protein Z is a plasma protein functioning as a carrier for ZPI. Protein Z also accelerates inhibitory effect of ZPI on factor Xa by 1000-fold. Inhibition of coagulation cascade via FXa by ZPI and other serpins is very important safety factor for normal homeostasis protecting human life against unwanted thrombosis. In the present work using native structure of PZ, ZPI, FXa and in a dynamic simulation, using NAMD software, the ternary complex was studied in an up to 10 nanoseconds protocol. Rely on trajectory analyses, we postulated that PZ binds ZPI by using its SP-like domain and through noncovalent forces. PZ then transfers ZPI through-out the blood, and by using its GLA domain and a bivalent cation of calcium, PZ binds to phospholipid bilayers (e.g., platelet) where the FXa is preallocated. In case of PZ-ZPI binding to plasma membrane, a series of complementary interactions take place between FXa, and PZ-ZPI complex including interactions between RCL loop of ZPI and catalytic site of FXa and some take place between long arm of PZ (composed of GLA, EGF1, and EGF2 domains) and GLA domain of FXa. In our claim these complementary interactions lead PZ to bind correctly to prelocated FXa.

Regulation of Immune Responses by Histone Deacetylase Inhibitors

Paul V. Licciardi and Tom C. Karagiannis — Sun, 18 Mar 2012 13:32:55 +0000

Both genetic and epigenetic factors are important regulators of the immune system. There is an increasing body of evidence attesting to epigenetic modifications that influence the development of distinct innate and adaptive immune response cells. Chromatin remodelling via acetylation, methylation, phosphorylation, and ubiquitination of histone proteins as well as DNA, methylation is epigenetic mechanisms by which immune gene expression can be controlled. In this paper, we will discuss the role of epigenetics in the regulation of host immunity, with particular emphasis on histone deacetylase inhibitors. In particular, the role of HDAC inhibitors as a new class of immunomodulatory therapeutics will also be reviewed.

18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Management of Aggressive Non-Hodgkin's B-Cell Lymphoma

M. J. Shelly, S. McDermott, O. J. O'Connor, and M. A. Blake — Sun, 11 Mar 2012 08:21:16 +0000

18-Fluorodeoxyglucose (FDG-PET/CT) is an established imaging modality that has been proven to be of benefit in the management of aggressive B-cell non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma and advanced stage follicular lymphoma. The combination of anatomic and functional imaging afforded by FDG-PET/CT has led to superior sensitivity and specificity in the primary staging, restaging, and assessment of response to treatment of hematological malignancies when compared to FDG-PET and CT alone. The use of FDG-PET/CT for posttreatment surveillance imaging remains controversial, and further study is needed to ascertain whether this modality is cost effective and appropriate for use in this setting.

Inhibition of LPS-Induced Activation of Coagulation by p38 MAPK Inhibitor

Mon, 05 Mar 2012 10:57:40 +0000

During Gram-negative sepsis, lipopolysaccharide (LPS) activates toll-like receptor (TLR) 4 and induces complex responses of immune system and coagulation. However, the underlying LPS signalling mechanism on coagulation activation remains complex. To determine the role of the intracellular signalling factors p38 mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and c-Jun N-terminal kinase (JNK) in the procoagulant response to LPS, coagulation process of human whole blood exposed to specific inhibitors was measured by thrombelastography. Samples were stimulated with LPS (100 μg/mL) after preincubation with BAY117082 (specific NF-κB inhibitor), SP600125 (specific JNK inhibitor), SB203580 (specific p38 MAPK inhibitor), or vehicle. SB203580 strongly inhibited LPS-induced coagulation activation, whereas BAY117082 and SP600125 showed no significant effect. Activation of p38 MAPK, NF-κB, and JNK and respective inhibitory effects were confirmed by Multi-Target Sandwich ELISA. In conclusion, activation of p38 MAPK is crucial for early LPS-induced activation of coagulation.