Carriers Of Hemoglobin Research Articles

Detection of Asymptomatic Sickle Cell Hemoglobin Carriers and Fetal Hemoglobin Regulating Genetic Variants in African Descendants from Oaxaca, Mexico.

Sickle cell anemia has been classified as a noninfectious neglected tropical disease and, although not exclusively, affects African descendants more frequently. This study aimed to detect asymptomatic sickle cell hemoglobin carriers (HbAS) in marginalized and vulnerable populations during a public health screening in African descendants from Oaxaca, Mexico, and to validate an amplification refractory mutation system (ARMS)-PCR methodology to detect fetal-hemoglobin (HbF)-regulating genetic variants in BCL11A toward affordable routine association of single nucleotide variants (SNVs) with HbF concentrations. To this aim, hemoglobin variants were detected by acidic citrate agar and alkaline cellulose acetate electrophoreses. SNVs in the hemoglobin subunit beta gene (HBB) were identified by the β-globin mutation detection assay (β-GMDA) and ARMS-PCR, respectively, and validated by Sanger sequencing. The association between genotypes and HbF concentrations was evaluated using Spearman's correlation coefficient. The results obtained during a directed screening in 140 self-identified African descendants revealed 42 HbS-carriers (30%), of which 39 showed normal total hemoglobin concentrations (92.8%), only 3 presented anemia (7.2%), and 9 showed quantifiable HbF concentration (21.4%). As validated by Sanger sequencing, the designed ARMS-PCR efficiently detected homozygous and heterozygous variants in BCL11A. In a cohort of 42 heterozygous (HbAS) and 27 healthy (HbAA) individuals from the same population, only one SNV (rs766432) showed statistically significant association with increasing HbF concentration, and two new unrelated homozygous silent variants were identified. This study reveals the need to raise coverage of HbS screening in vulnerable populations and shows a feasible low-cost ARMS-PCR methodology to determine the presence of SNVs in quantitative trait loci affecting HbF.

Biomarker of Anopheles exposure in Ghanaian children with hemoglobin S and C

Heterozygous carriers of hemoglobin S and C (HbAS and HbAC) have a reduced risk of severe malaria but are not protected from Plasmodium falciparum infection, suggesting that the protection involves acquired immunity. During a blood meal, female Anopheles mosquitoes inject saliva that can elicit a host antibody response, which can serve as a proxy for exposure to Plasmodium infection. Previous studies have shown that the peptide gSG6-P1 of An. gambiae saliva is antigenic and highly Anopheles specific. Here, we used plasma samples from 201 Ghanaian children with wild-type hemoglobin (HbAA), HbAS, and HbAC to evaluate antibody levels against gSG6-P1 as a serological biomarker of Anopheles exposure and, therefore of P. falciparum infection risk. Malaria antigen (PfCSP, GLURP, Pfs230, and HB3VAR06)-specific IgG levels, demographic data, and data regarding P. falciparum infection and malaria control practices were also analyzed. Children with active P. falciparum infection had higher antibody levels against all antigens, and those with HbAS and HbAC had significantly higher antibody levels against Pfs230. Pfs230-specific IgG correlated negatively with gSG6-P1-specific IgG in children with HbAC. Our results highlight the importance of studying the role of hemoglobinopathies in malaria transmission to improve control interventions.

Red Blood Cell Substitutes: Liposome Encapsulated Hemoglobin and Magnetite Nanoparticle Conjugates as Oxygen Carriers.

The established blood donation and transfusion system has contributed a lot to human health and welfare, but for this system to function properly, it requires a sufficient number of healthy donors, which is not always possible. Pakistan was a country hit hardest by COVID-19 which additionally reduced the blood donation rates. In order to address such challenges, the present study focused on the development of RBC substitutes that can be transfused to all blood types. This paper reports the development and characterization of RBC substitutes by combining the strategies of conjugated and encapsulated hemoglobin where magnetite nanoparticles would act as the carrier of hemoglobin, and liposomes would separate internal and external environments. The interactions of hemoglobin variants with bare magnetite nanoparticles were studied through molecular docking studies. Moreover, nanoparticles were synthesized, and hemoglobin was purified from blood. These components were then used to make conjugates, and it was observed that only the hemoglobin HbA1 variant was making protein corona. These conjugates were then encapsulated in liposomes to make negatively charged RBC substitutes with a size range of 1-2 μm. Results suggest that these RBC substitutes work potentially in a similar way as natural RBCs work and can be used in the time of emergency.

Frequency of carrier state of thalassemia and various hemoglobinopathies in tertiary care hospital of Pakistan.

Background: It has been estimated that 5% of the global population are carriers of Hemoglobin (Hb) disorders. These disorders may cause hemolytic anemia leading to the critical condition of the patients. The current research was designed to identify spectrums of thalassemia minor and carriers of other hemoglobinopathies patients presenting at the tertiary care center to evaluate anemia.
 Methodology: A total of 3289 patients’ data with low Hb values and suspicion of hemoglobinopathies were included in this cross-sectional retrospective study. Complete blood count (CBC), High-performance liquid chromatography (HPLC), and sickling test were utilized in this study. At the same time, Patients with normal Hb as per HPLC analysis were excluded from this study.
 Results: Of the total, 708 (21.5%) patients had hemoglobin disorder and the mean age of patients with thalassemia minor was 24.0 ± 14.7 years. Out of 708 carriers, 646 (19.6%) cases showed traits of thalassemia minor, 12 (0.36%) showed Hb S trait, 43 (1.30%) showed Hb D trait, 07 (0.21%) showed Hb E trait, whereas there were no cases of Hb C recorded in this study.
 Conclusion: Thalassemia trait was the highest among other variants in our study population. It is recommended that to decrease the frequency of hemoglobinopathies, pre-marriage screening should be conducted, and family marriages should be restricted.

Assessment of Iron Status in Hemoglobin E and b Thalassemia Carriers

Background: About 10-13% people of Bangladesh are carrier of HbE and b- thalassaemia. Many program have been taken by Government and NGOs for supplementation of iron to raise hemoglobin level of children which may not be beneficial or might be harmful to the carriers of this disease.
 Objectives: of the study was to assess the iron status of Hemoglobin E and b thalassemia carriers thereby to develop iron supplementation strategy for these carriers.
 Methods: This cross sectional analytic study was on 206 carriers of Hemoglobin E and b thalassemia and 54 healthy controls. Complete blood count with RBC indices, Hemoglobin (Hb) electrophoresis and serum ferritin, serum iron and TIBC were carried out for all subjects following standard protocol. Data were analyzed by Statistical Package for Social Science (SPSS) Version 12.
 Results: Among 260 subjects 206 were carriers and 54 were control. Number of male was 137 and female was 123 and male to female ratio was 1.1:1. Age of the subjects ranges from 1 year to 59 years with a mean age (±SEM) of 23.07± 0.84 years. Mean age (±SEM) of cases was 22.78 ± 0.971 years and that of control was 24.17 ± 1.63 years. Hematological parameters such as mean (±SEM) Hb concentration, MCV, MCH, and MCHC of carriers were significantly low as compared to the control (p value < 0.01 in all comparison). Mean serum ferritin and iron level in carriers were higher than control however; statistical significance between the values were not found (p value >0.5). Out of 206 carriers 27 (13.1%) cases had IDA and it’s frequency was similar among HbE (14.2%) and thalassemia carriers (12.2%) and prevalence of IDA among the carriers were high (37.5 %) in age group 1-5 years which rises to 52.5% in under nourished children.
 Conclusion: Carriers of HbE and b thalassemia do have relatively higher iron profile as compared to control but not statistically significant. Iron deficiency anemia is not uncommon in carriers especially in children. So there is no contraindication of iron supplementation to the children in general.
 DS (Child) H J 2020; 36(1) : 25-33

Distribution of msp1, msp2 and eba175 Allelic Family According to Hemoglobin Genotype and G6PD Type from Children with Uncomplicated Malaria in Banfora Heath District (Burkina Faso)

Aim: The present study aimed to evaluate the Plasmodium falciparum genetic diversity according to the host hemoglobin and G6PD genetic variants during the course of malaria in infected children aged from 2 to 10 years and living in endemic area in Burkina Faso.
 Study Design: The study was designed as a longitudinal follow up conducted between May 2015 and February 2016 in Banfora health district, Burkina Faso.
 Methodology: We included 136 subjects (73 males and 63 females; age range from 2-10 years). Blood thick and thin film was done by capillary blood. Venous blood was collected for DNA extraction. Malaria diagnosis was done by microscopy. Human and parasite DNA were extracted based on Qiagen kit procedure. Then, hemoglobin and G6PD were genotyped by RLFP-PCR while the msp1, msp2 and eba175 genes were typed by a nested PCR. All PCR products were analyzed by electrophoresis on a 1.5-2% agarose gel and alleles categorized according to the molecular weight.
 Results: The prevalence of hemoglobin type was 19.11% for abnormal hemoglobin and 80.9% for normal hemoglobin carriage. The prevalence of G6PD type was 91.18% for normal and 8.82% for G6PD deficiency carriage, respectively. The prevalence of msp1 allelic families was 81.60%, 80.80% and 67.20% for k1, ro33 and mad20 respectively while for msp2 gene, fc27 and 3D7 allelic family the prevalence was 70.53% and 69.64% respectively. The eba175 allelic families’ distribution showed 77.31% and 40.21% for fcr3 and Camp respectively. There was no difference in multiplicity of infection (MOI) according to hemoglobin genotypes and G6PD types. We found that k1 was the predominant allelic family of msp1 in normal hemoglobin genotype (AA) and normal G6PD type. The mixed infection of eba175 was statistically higher in abnormal hemoglobin (p=0.04). There was no statistical difference between fcr3 and camp prevalence excepted in G6PD deficient type. The polymorphism results showed that the prevalence of 450 bp in fc27 was statistically significantly higher in normal hemoglobin variant carriers (AA) than abnormal hemoglobin carriers (p=2.10 -4)). However, the prevalence of 350 bp in fc27 was statistically higher in normal G6PD than deficient G6PD carriers (p=0.034).
 Conclusion: Our result showed that the distribution of msp1 and eba75 polymorphism could be influenced by hemoglobin and G6PD variants. These results suggest that hemoglobin and G6PD could influence P. falciparum genetic diversity.

HemoTypeSC, a low-cost point-of-care testing device for sickle cell disease: Promises and challenges

BackgroundSickle cell disease (SCD) is a neglected burden of growing importance. >312,000 births are affected annually by sickle cell anaemia (SCA). Early interventions such as newborn screening, penicillin prophylaxis and hydroxyurea can substantially reduce the mortality and morbidity associated with SCD. Nevertheless, their implementation in African countries has been mostly limited to pilot projects. Recent development of low-cost point-of-care testing (POCT) devices for sickle haemoglobin (HbS) could greatly facilitate the diagnosis of those affected. MethodsWe conducted the first multi-centre, real-world assessment of a low-cost POCT device, HemoTypeSC, in a low-income country. Between September and November 2017, we screened 1121 babies using both HemoTypeSC and HPLC and confirmed discordant samples by molecular diagnosis. FindingsWe found that, in optimal field conditions, the sensitivity and specificity of the test for SCA were 93.4% and 99.9%, respectively. All 14 carriers of haemoglobin C were successfully identified. Our study reveals an overall accuracy of 99.1%, but also highlights the importance of rigorous data collection, staff training and accurate confirmatory testing. It suggests that HPLC results might not be as reliable in a resource-poor setting as usually considered. InterpretationThe use of such a POCT device can be scaled up and routinely used across multiple healthcare centres in sub-Saharan Africa, which would offer great potential for the identification and management of vast numbers of individuals affected by SCD who are currently undiagnosed. Funding USImperial College London's Wellcome Trust Centre for Global Health Research (grant #WMNP P43370).

Donor Cell Myeloma: A Unique Case

Leukemia relapse occurring in donor cells, so called donor cell leukemia (DCL) after allogeneic hematopoietic stem cell transplantation has been previously reported in the literature. Some authors have suggested that the development of DCL is perhaps a more common occurrence than traditionally thought. Donor cell myeloma (DCM) seems to be less frequent than DCL. This 46-year old male when first seen in 2000 was diagnosed with stage IIIa multiple myeloma. A monoclonal IgA kappa spike was recorded at diagnosis. Treatment with melphalan and prednisone was delivered every four to six weeks for a total of 22 courses. Fourty months after the initial diagnosis, an M2 acute myelogenous leukemia was identified. Treatment with chemotherapy resulted in complete remission. Matched UCB cells were localized at the London Cord Blood Bank. The UCB belonged to a male product of a white western European mother and a black Nigerian father who was a carrier of hemoglobin S. Hemoglobins A, F and S were detected in the UCB, consonant with sickle cell trait. The patient was allografted employing the “Mexican” NST conditioning regimen, granulocyte count recovered to more than 0.5 x 109/L on day 14, with the platelet count never dropping below 20 x 109/L. On day +40, the polymorphic microsatellite markers revealed mixed chimerism. The hemoglobin S gene was identified on day +20 and on day +60, full chimerism was shown. Cyclosporine A was stopped on day +350. The patient returned 170 months after the transplant with low back pain and the bone marrow aspiration disclosed 80% abnormal plasma cells, an IgA kappa monoclonal spike of 3.1 gr/dl, and complete chimerism. Malignant plasma cells were sorted by means of flow cytometry before genetic fingerprinting; cells were stained with an admixture of fluorescent monoclonal antibodies and cells co-expressing dim CD45, bright CD38 and CD56 were sorted out to ≥99% purity. Sorted cells were shown to have donor origin (Figure 1). The patient was treated with thalidomide, dexamethasone and bortezomib and the monoclonal spike disappeared; an autologous stem cell transplant is planned. Most people consider that the development of a malignancy in the cells of the donor is a rare event and very few prospective studies have analyzed the real prevalence of this phenomenon. Prospectively, we have found that 7% (95% CI 2.9 to 13.6%) of patients with leukemic activity after an allogeneic graft do have a donor cell-derived leukemia; this figure contrasts with those described elsewhere in non-prospective studies. A major problem in the analysis of donor cell derived malignancies is that demonstration of the donor cell origin of malignant activity. In this case, the demonstration of DNA of the donor in the fluorescence-activated sorted malignant plasma cells is indicative of the origin of the myeloma cells. Interestingly, the immunoglobulin type produced by the initial myeloma cells is the same as that of the donor-cell myeloma; Despite being two myelomas producing the same immunoglobulin subtype, both should be considered as de novomalignancies and as such, treated; we have previously shown that donor cell leukemias do have a response when treated as de novo, non-secondary leukemias. To our best knowledge, this is the second report of DCM following allogeneic HSCT. Prior to this case, Kim et al reported a DCM after an allogeneic transplant in a patient with refractory anemia with ringed sideroblasts. Previously, two cases have been reported of donor-origin MM, but they occurred in patients who underwent solid organ transplantation of the kidney and heart-lung. Kumar et alreported a case of DCM developing after unrelated allogeneic HSCT in the both donor and recipient but they did not conducted a comprehensive molecular cytogenetic study. In the case published by Maestas et al, an abnormal proliferation of plasma cells was identified in the donor, thus making possible that a malignant plasma cell clone was already present in the donor stem cells. In summary, we have clearly shown that this patient has had three different malignancies: 1) De novomultiple myeloma, 2) Secondary acute myelogenous leukemia and 3) De novodonor cell-derived multiple myeloma. The mechanisms involved in these episodes could be useful to better understand tumorigenesis. DisclosuresNo relevant conflicts of interest to declare.

Perception des lésions oculaires cécitantes de la drépanocytose par les praticiens hospitalo-universitaire de Dakar

In Senegal, 10% of the population are said to be carriers of hemoglobin S, the most widespread hemoglobinopathy in the world. It is responsible for potentially blinding ophthalmological manifestations. Few practitioners refer patients for ophthalmologic screening. The goal of our study was to assess the level of knowledge of practitioners of the blinding ocular lesions of sickle cell disease. A cross-sectional prospective study was carried out over five months. It included Dakar university hospital practitioners aside from ophthalmologists. On the survey form, each practitioner specified his or her specialty and responded to eight questions regarding sickle cell patients seen in consultation, knowledge of the blinding lesions related to the disease, and ocular monitoring for blinding systemic diseases. The practitioners were divided into three groups: department of medicine and medical specialties (group I), surgery and surgical specialties (group II), and biology and functional testing (group III). The descriptive analysis was done with the EPI-INFO software version 6.04. The participation rate was 45.88%. Group I represented 45.29% of the sample, Group II 35.85% and Group III 18.86%. In all, 87.73% of practitioners saw sickle cell patients in consultation, 75.47% were aware of ocular involvement related to sickle cell disease, and 58.49% were aware of blinding lesions. 94.62% of practitioners saw sickle cell disease patients without systematically recommending ophthalmological consultation. Practitioners' level of knowledge of the blinding ocular lesions of sickle cell disease is considered to be low.

Nucleated Teleost Erythrocytes Play an Nk-Lysin- and Autophagy-Dependent Role in Antiviral Immunity.

With the exception of mammals, vertebrate erythrocytes are nucleated. Nevertheless, these cells are usually considered as mere carriers of hemoglobin. In this work, however, we describe for the first time an unrecognized role of teleost red blood cells (RBCs). We found that Nk-lysin (Nkl), an antimicrobial peptide produced by NK-cells and cytotoxic T-lymphocytes, was also expressed in flatfish turbot (Scophthalmus maximus) erythrocytes. Although the antiviral role of Nkl remains to be elucidated, we found a positive correlation between the transcription of nkl and the resistance to an infection with Rhabdovirus in a teleost fish. Surprisingly, Nkl was found to be present in the autophagolysosomes of erythrocytes, and therefore this higher resistance provided by Nkl could be related to autophagy. The organelles of RBCs are degraded through autophagy during the maturation process of these cells. In this work, we observed that the blockage of autophagy increased the replication of viral hemorrhagic septicemia virus in nucleated teleost erythrocytes, which suggests that this mechanism may also be a key process in the defense against viruses in these cells. Nkl, which possesses membrane-perturbing ability and was affected by this modulation of RBC autophagy, could also participate in this process. For the first time, autophagy has been described not only as a life cycle event during the maturation of erythrocytes but also as a pivotal antiviral mechanism in nucleated erythrocytes. These results suggest a role of erythrocytes and Nkl in the antiviral immunity of fish and other vertebrates with nucleated RBCs.

Cardiometabolic and Hemostatic Profiles of Women Carriers of Hemoglobin Variants Using Combined Oral Contraceptives

Introduction: Several studies reported combined contraceptives influence in hemostatic and lipid profile besides the concern about the thromboembolism and cardiovascular risks due to the steroids hormones use. As women with hemoglobin (Hb) variants have a pre-existing inflammatory condition and considering the high frequency of hemoglobin variant worldwide, this study aims to evaluate the association of hematological, lipid, glicemic, inflammatory and hemostatic profiles in women using combined oral contraceptives and carriers of hemoglobin variants.Methods: We performed a cross-sectional study including 591 women in reproductive-age. We investigated their hemoglobin profile and COCs use. Of them, we included 60 women with HbAA, 21 with HbAC, 25 with HbAS and 7 with HbSC profiles, all of them combined oral contraceptives users. Among those combined oral contraceptives nonusers, 9 were HbAC and 19 HbSC. We evaluated fasting serum glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), C-reactive protein (CRP), fibrinogen, D-dimer and hematological profile among the studied groups. This study was conducted in accordance and approved by the Research Ethics Committee of the Fundação Oswaldo Cruz - FIOCRUZ, Brazil; and also with the Helsinki Declaration of 1975, and its revisions. Mann-Whitney U tests were used to compare two groups of values within the same variable.Results: We observed significant differences in some hematological and cardiometabolic parameters in women carriers of different Hb variants and using COCs. We found relevant increases in CRP levels in HbSC and HbAC women that seem to be associated with different types of progestins present in combined oral contraceptives formulations. Also, combined oral contraceptives use seems to be associated with decreased HDL-c levels in HbAC women. Otherwise, D-dimer levels were increased in all women with Hb variants, independently of the contraceptive use.Conclusions: Although combined oral contraceptive remains an important method to prevent unintended pregnancy, our data suggest that contraception in women carriers of Hb variants, including those in heterozygosis, should be carefully evaluated, especially, considering the pre-existent inflammatory and pro-thrombotic conditions that together with combined oral contraceptive use may result in additional health problems, such as cardiovascular and thromboembolic diseases. DisclosuresNo relevant conflicts of interest to declare.

Citrate metabolism in red blood cells stored in additive solution-3.

Red blood cells (RBCs) are thought to have a relatively simple metabolic network compared to other human cell types. Recent proteomics reports challenge the notion that RBCs are mere hemoglobin carriers with limited metabolic activity. Expanding our understanding of RBC metabolism has key implications in many biomedical areas, including transfusion medicine. In-gel digestion coupled with mass spectrometric analysis proteomics approaches were combined with state-of-the-art tracing experiments by incubating leukofiltered RBCs in additive solution-3 for up to 42 days under blood bank conditions, in presence of 13 C1,2,3 -glucose, 2,2,4,4-d-citrate, and 13 C,15 N-glutamine. Results indicate that the pentose phosphate pathway/glycolysis ratio increases during storage in additive solution-3. While the majority of supernatant glucose is consumed to fuel glycolysis, incorporation of glucose-derived pentose phosphate moieties was observed in nucleoside monophosphates. Incubation with deuterated citrate indicated that citrate uptake and metabolism contribute to explain the origin of up to approximately 20% to 30% lactate that could not be explained by glucose oxidation and 2,3-diphosphoglycerate consumption alone. Incubation with 13 C,15 N-glutamine showed that glutaminolysis fuels transamination reactions and accumulation of millimolar levels of 5-oxoproline, while de novo glutathione synthesis was not significantly active during refrigerated storage. Quantitative tracing metabolic experiments revealed that mature RBCs can metabolize other substrates than glucose, such as citrate, an observation relevant to transfusion medicine (i.e., formulation of novel additives), and other research endeavors where metabolic modulation of RBCs opens potential avenues for therapeutic interventions, such as in sickle cell disease.

Investigating alpha-globin structural variants: a retrospective review of 135,000 Brazilian individuals.

BackgroundBrazil has a multiethnic population with a high diversity of hemoglobinopathies. While screenings for beta-globin mutations are far more common, alterations affecting alpha-globin genes are usually more silent and less well known. The aim of this study was to describe the results of a screening program for alpha-globin gene mutations in a representative sample of the Southeastern Brazilian population.MethodsA total of 135,000 individuals, including patients with clinical suspicion of hemoglobinopathies and their family members, randomly chosen individuals submitted to blood tests and blood donors who were abnormal hemoglobin carriers were analyzed. The variants were screened by alkaline and acid electrophoreses, isoelectric focusing and cation-exchange high performance liquid chromatography (HPLC) and the abnormal chains were investigated by reverse-phase high performance liquid chromatography (RP-HPLC). Mutations were identified by molecular analyses, and the oxygen affinity, heme–heme cooperativity and Bohr effect of the variants were evaluated by functional tests.ResultsFour new and 22 rare variants were detected in 98 families. Some of these variants were found in co-inheritance with other hemoglobinopathies. Of the rare hemoglobins, Hasharon, Stanleyville II and J-Rovigo were the most common, the first two being S-like and associated with alpha-thalassemia.ConclusionThe variability of alpha-globin alterations reflects the high degree of racial miscegenation and an intense internal migratory flow between different Brazilian regions. This diversity highlights the importance of programs for diagnosing hemoglobinopathies and preventing combinations that may lead to important clinical manifestations in multiethnic populations.

Engineering the oxygen sensing regulation results in an enhanced recombinant human hemoglobin production by Saccharomyces cerevisiae.

Efficient production of appropriate oxygen carriers for transfusions (blood substitutes or artificial blood) has been pursued for many decades, and to date several strategies have been used, from synthetic polymers to cell-free hemoglobin carriers. The recent advances in the field of metabolic engineering also allowed the generation of different genetically modified organisms for the production of recombinant human hemoglobin. Several studies have showed very promising results using the bacterium Escherichia coli as a production platform, reporting hemoglobin titers above 5% of the total cell protein content. However, there are still certain limitations regarding the protein stability and functionality of the recombinant hemoglobin produced in bacterial systems. In order to overcome these limitations, yeast systems have been proposed as the eukaryal alternative. We recently reported the generation of a set of plasmids to produce functional human hemoglobin in Saccharomyces cerevisiae, with final titers of active hemoglobin exceeding 4% of the total cell protein. In this study, we propose a strategy for further engineering S. cerevisiae by altering the oxygen sensing pathway by deleting the transcription factor HAP1, which resulted in an increase of the final recombinant active hemoglobin titer exceeding 7% of the total cellular protein.

Systemic oxygen delivery by peritoneal perfusion of oxygen microbubbles

Severe hypoxemia refractory to pulmonary mechanical ventilation remains life-threatening in critically ill patients. Peritoneal ventilation has long been desired for extrapulmonary oxygenation owing to easy access of the peritoneal cavity for catheterization and the relative safety compared to an extracorporeal circuit. Unfortunately, prior attempts involving direct oxygen ventilation or aqueous perfusates of fluorocarbons or hemoglobin carriers have failed, leading many researchers to abandon the method. We attribute these prior failures to limited mass transfer of oxygen to the peritoneum and have designed an oxygen formulation that overcomes this limitation. Using phospholipid-coated oxygen microbubbles (OMBs), we demonstrate 100% survival for rats experiencing acute lung trauma to at least 2 h. In contrast, all untreated rats and rats treated with peritoneal oxygenated saline died within 30 min. For rats treated with OMBs, hemoglobin saturation and heart rate were at normal levels over the 2-h timeframe. Peritoneal oxygenation with OMBs was therefore shown to be safe and effective, and the method requires less equipment and technical expertise than initiating and maintaining an extracorporeal circuit. Further translation of peritoneal oxygenation with OMBs may provide therapy for acute respiratory distress syndrome arising from trauma, sepsis, pneumonia, aspiration, burns and other pulmonary diseases.

Estudo de microcitose numa população jovem adulta assintomática

EVALUATION OF MICROCYTOSIS IN AN ASYMPTOMATIC YOUNG ADULT POPULATION Aim: To identify the causes of microcytosis in an asymptomatic young adult population. Population and Methods: Candidates for induction into the Portuguese army who had passed the induction physical examination were included in this study. For subjects with a mean corpuscular volume less than 80fL (microcytosis), analyses of serum iron, ferritin and hemoglobin electrophoresis were performed. Cases were grouped according to possible causes of microcytosis. Data on birthplace and place of residence were recorded. Descriptive statistics were analyzed with SPSS software. Results:We studied 2558 subjects. The prevalence of microcytosis was 3,2% (N=81) in this population, we identified four diagnostic groups. Group I (N=12, 15%) included ten subjects with hemoglobin S (70% from Lisbon and Setubal), a carrier of hemoglobin C (from Lisbon) and a carrier of hemoglobin Lepore (from Santarem). Group II (N=16, 20%) was composed of heterozygous carriers of s-thalassemia, mostly from Faro. Subjects in Group III (N=21, 26%) were mostly from Lisbon, with ferritin below 15ng/mL and were characterized by iron deficiency anemia. Group IV (N=32, 40%) included subjects with normal serum iron, ferritin and hemoglobin electrophoresis, suspected of being carriers of a-thalassemia, mostly from Lisbon. Conclusion: The evaluation of microcytosis in an asymptomatic young adult population using simple and inexpensive methods was robust enough to identify subjects with genetic abnormalities and iron deficiency. This study contributes to a better epidemiologic understanding of this population. It enables the introduction of preventive and health-promoting measures such as counselling and genetic guidance.

Beta globin haplotypes in hemoglobin S carriers in Colombia

Introduction. HbS mutation is accompanied by other mutations in the region of chromosome 11 known as "beta globin cluster". The pattern of combination of these polymorphisms giving rise to the haplotypes that co-inherit the HbS mutation, are called haplotypes s and are of great epidemiological and clinical significance.Objective. To determine the frequency of major haplotypes associated with S beta-globin gene in Colombian patients heterozygous for hemoglobin S. Materials and methods. Within the national neonatal screening program at Clínica Colsanitas, nearly 1,200 children have been studied in search of hemoglobinopathies, finding the sickle cell trait as the most common hemoglobinopathy. S beta-globin gene haplotypes were determined by PCR and restriction enzymes, in 33 children with AS hemoglobin electrophoretic patterns. Also electrophoretic patterns of hemoglobin, fetal hemoglobin levels and hematologic parameters of each individual were identified.Results. The most frequent haplotypes in Colombia are of African origin the Bantú haplotype (36.4 %), followed by Senegal (30.3 %), Benin (21.2 %) and Cameroon (12.1 %). Hemoglobin electrophoresis confirmed the AS phenotype in all patients, and the dosing showed fetal hemoglobin levels below 1%. Hematological parameters analyzed showed normal values in all cases. Conclusion. The frequency of haplotypes found in mixed population carriers of hemoglobin S differ both in rate and order of appearance, as compared with what was reported more than ten years ago in a Colombian caribbean population with sickle cell anemia.

Sickle Cell Trait-Associated Deaths: A Case Series with a Review of the Literature*,†

This study presents a series of 16 carriers of hemoglobin S (HbS) who died during various circumstances. Many of the cases were associated with mild to moderate exertion. The onset and/or duration of symptoms varied from a few minutes to several hours with many displaying a prolonged lucid interval with stable vital signs. Despite seeking medical treatment, sickle cell trait-related micro-occlusive crisis was never considered in the differential diagnosis. Several cases were associated with sudden death. In those deaths which were delayed, high anion gap and uncompensated metabolic acidosis were typical and were not heat related. Also characteristic were large increases in creatine kinase, alanine aminotransferase, and aspartate aminotransferase along with myoglobinemia. Although the antemortem diagnosis of rhabdomyolysis was made, the underlying cause was never deduced by the clinicians. The sickling found at autopsy is not always a postmortem artifact, and in the right circumstances can be diagnostic.

Levels of glycated haemoglobin A – HbA1c in nondiabetic carriers of haemoglobin O‐Arab

International Journal of Laboratory HematologyVolume 31, Issue 4 p. 471-474 Levels of glycated haemoglobin A – HbA1c in nondiabetic carriers of haemoglobin O-Arab A. Agorasti, A. Agorasti General Hospital of Xanthi – Haematology Laboratory, Neapolis Xanthi Thrace 67100, GreeceE-mail: [email protected]Search for more papers by this authorT. Trivellas, T. Trivellas Technological Institute of Kavala, Kavala, GreeceSearch for more papers by this authorV. Papadopoulos, V. Papadopoulos Department of Internal Medicine, Democritus University of Thrace – University Hospital of Alexandroupolis, Alexandroupolis, GreeceSearch for more papers by this authorD. Konstantinidou, D. Konstantinidou General Hospital of Xanthi – Haematology Laboratory, Neapolis Xanthi Thrace 67100, GreeceE-mail: [email protected]Search for more papers by this author A. Agorasti, A. Agorasti General Hospital of Xanthi – Haematology Laboratory, Neapolis Xanthi Thrace 67100, GreeceE-mail: [email protected]Search for more papers by this authorT. Trivellas, T. Trivellas Technological Institute of Kavala, Kavala, GreeceSearch for more papers by this authorV. Papadopoulos, V. Papadopoulos Department of Internal Medicine, Democritus University of Thrace – University Hospital of Alexandroupolis, Alexandroupolis, GreeceSearch for more papers by this authorD. Konstantinidou, D. Konstantinidou General Hospital of Xanthi – Haematology Laboratory, Neapolis Xanthi Thrace 67100, GreeceE-mail: [email protected]Search for more papers by this author First published: 22 June 2009 https://doi.org/10.1111/j.1751-553X.2008.01065.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Volume31, Issue4August 2009Pages 471-474 RelatedInformation

Comparison of glycated albumin and hemoglobin A1c levels in diabetic subjects on hemodialysis

Glycated albumin is thought to more accurately reflect glycemic control in diabetic hemodialysis patients than hemoglobin A(1c) because of shortened red cell survival. To test this, glycated hemoglobin and albumin levels were measured in blood samples collected from 307 diabetic subjects of whom 258 were on hemodialysis and 49 were without overt renal disease. In diabetic subjects with renal disease, relative to those without, the mean serum glucose and glycated albumin concentrations were significantly higher while hemoglobin A(1c) tended to be lower. The glycated albumin to hemoglobin A(1c) ratio was significantly increased in dialysis patients compared with the controls. Hemoglobin A(1c) was positively associated with hemoglobin and negatively associated with the erythropoietin dose in hemodialysis patients, whereas these factors and serum albumin did not significantly impact glycated albumin levels. Using best-fit multivariate models, dialysis status significantly impacted hemoglobin A(1c) levels without a significant effect on glycated albumin. Our results show that in diabetic hemodialysis patients, hemoglobin A(1c) levels significantly underestimate glycemic control while those of glycated albumin more accurately reflect this control.