The culminating step of the intraerythrocytic development of Plasmodium falciparum, the causative agent of malaria, is the spectacular release of multiple invasive merozoites on rupture of the infected erythrocyte membrane. This work reports for the first time that the whole process, taking place in time scales as short as 400 milliseconds, is the result of an elastic instability of the infected erythrocyte membrane. Using high-speed differential interference contrast (DIC) video microscopy and epifluorescence, we demonstrate that the release occurs in 3 main steps after osmotic swelling of the infected erythrocyte: a pore opens in similar to 100 milliseconds, ejecting 1-2 merozoites, an outward curling of the erythrocyte membrane is then observed, ending with a fast eversion of the infected erythrocyte membrane, pushing the parasites forward. It is noteworthy that this last step shows slight differences when infected erythrocytes are adhering. We rationalize our observations by considering that during the parasite development, the infected erythrocyte membrane acquires a spontaneous curvature and we present a subsequent model describing the dynamics of the curling rim. Our results show that sequential erythrocyte membrane curling and eversion is necessary for the parasite efficient angular dispersion and might be biologically essential for fast and numerous invasions of new erythrocytes. (Blood. 2011;117(15):4118-4124)
Prior to diagnosis, patients with haematological cancers often have multiple primary care consultations, resulting in diagnostic delay. They are less likely to be referred urgently to hospital and often present as emergencies. We examined patient perspectives of time to help-seeking and diagnosis, as well as associated symptoms and experiences. The UK's Haematological Malignancy Research Network (http://www.hmrn.org) routinely collects data on all patients newly diagnosed with myeloma, lymphoma and leukaemia (>2000 annually; population 3.6 million). With clinical agreement, patients are also invited to participate in an on-going survey about the circumstances leading to their diagnosis (presence/absence of symptoms; type of symptom(s) and date(s) of onset; date medical advice first sought (help-seeking); summary of important experiences in the time before diagnosis). From 2004-2011, 8858 patients were approached and 5038 agreed they could be contacted for research purposes; 3329 requested and returned a completed questionnaire. The duration of the total interval (symptom onset to diagnosis), patient interval (symptom onset to help-seeking) and diagnostic interval (help-seeking to diagnosis) was examined by patient characteristics and diagnosis. Type and frequency of symptoms were examined collectively, by diagnosis and compared to UK Referral Guidelines. Around one-third of patients were asymptomatic at diagnosis. In those with symptoms, the median patient interval tended to be shorter than the diagnostic interval across most diseases. Intervals varied markedly by diagnosis: acute myeloid leukaemia being 41 days (Interquartile range (IQR) 17-85), diffuse large B-cell lymphoma 98 days (IQR 53-192) and myeloma 163 days (IQR 84-306). Many symptoms corresponded to those cited in UK Referral Guidelines, but some were rarely reported (e.g. pain on drinking alcohol). By contrast others, absent from the guidance, were more frequent (e.g. stomach and bowel problems). Symptoms such as tiredness and pain were common across all diseases, although some specificity was evident by sub-type, such as lymphadenopathy in lymphoma and bleeding and bruising in acute leukaemia. Pathways to diagnosis are varied and can be unacceptably prolonged, particularly for myeloma and some lymphomas. More evidence is needed, along with interventions to reduce time-to-diagnosis, such as public education campaigns and GP decision-making aids, as well as refinement of existing Referral Guidelines.
Knowledge of the factors associated with health-related quality of life (HRQOL) among patients with thalassemia is essential in developing more suitable clinical, counseling, and social support programs to improve treatment outcomes of these patients. In light of the limited research in this area, this study aims to examine factors associated with HRQOL among children and adolescents with thalassemia in Thailand. A cross-sectional survey was conducted in three selected hospitals in Thailand during June to November 2006. PedsQL 4.0 Generic Core Scale (Thai version) was used to assess HRQOL in 315 thalassemia patients between 5 and 18 years of age. Other related clinical characteristics of the patients were collected via medical record review. The mean (SD) of the total summary score was 76.67 (11.40), while the means (SD) for the Physical Health Summary score and Psychosocial Health Summary score were 78.24 (14.77) and 75.54 (12.76), respectively. The school functioning subscale scored the lowest, with a mean of 67.89 (SD = 15.92). The following factors significantly affected the HRQOL of the patients: age; age at onset of anemia and age at first transfusion; pre-transfusion hemoglobin (Hb) level; receiving a blood transfusion during the previous three months; and disease severity. In addition, iron chelation therapy had a significant negative effect on HRQOL in the school functioning subscale. In contrast, serum ferritin level, frequency of blood transfusions per year, and gender were not significantly related to HRQOL among these patients. The results from multivariate analysis also confirmed these findings. To improve HRQOL of thalassemia patients, suitable programs aimed at providing psychosocial support and a link between the patient, school officials, the family and the physician are important, especially in terms of improving the school functioning score. The findings also confirmed the importance of maintaining a pre-transfusion Hb level of at least 9-10.5 g/dL. In addition, special care and attention should be given to patients with a severe condition, and those who are receiving subcutaneous iron chelation therapy.
Influenza vaccines are recommended for administration by the intramuscular route. However, many physicians use the subcutaneous route for patients receiving an oral anticoagulant because this route is thought to induce fewer hemorrhagic side effects. Our aim is to assess the safety of intramuscular administration of influenza vaccine in patients on oral anticoagulation therapy. Randomised, controlled, single blinded, multi-centre clinical trial. 4 primary care practices in Barcelona, Spain. 229 patients on oral anticoagulation therapy eligible for influenza vaccine during the 2003-2004 season. intramuscular administration of influenza vaccine in the experimental group (129 patients) compared to subcutaneous administration in the control group (100 patients). change in the circumference of the arm at the site of injection at 24 hours. appearance of local reactions and pain at 24 hours and at 10 days; change in INR (International Normalized Ratio) at 24 hours and at 10 days. Analysis was by intention to treat using the 95% confidence intervals of the proportions or mean differences. Baseline variables in the two groups were similar. No major side effects or major haemorrhage during the follow-up period were reported. No significant differences were observed in the primary outcome between the two groups. The appearance of local adverse reactions was more frequent in the subcutaneous administration group (37,4% vs. 17,4%, 95% confidence interval of the difference 8,2% to 31,8%). This study shows that the intramuscular administration route of influenza vaccine in patients on anticoagulant therapy does not have more side effects than the subcutaneous administration route. NCT00137579 at clinicaltrials.gov.
Hypogammaglobulinemia may be part of several different immunological or malignant conditions, and its origin is not always obvious. Furthermore, although autoimmune cytopenias are known to be associated with common variable immunodeficiency (CVID) and even may precede signs of immunodeficiency, this is not always recognized. Despite novel insight into the molecular immunology of common variable immunodeficiency, several areas of uncertainty remain. In addition, the full spectrum of immunological effects of the B cell depleting anti-CD20 antibody Rituximab has not been fully explored. To our knowledge this is the first report of development of CVID in a patient with normal immunoglobulin prior to Rituximab treatment. Here we describe the highly unusual clinical presentation of a 34-year old Caucasian male with treatment refractory immune thrombocytopenic purpura and persistent lymphadenopathy, who was splenectomized and received multiple courses of high-dose corticosteroid before treatment with Rituximab resulted in a sustained response. However, in the setting of severe pneumococcal meningitis, hypogammaglobulinemia was diagnosed. An extensive immunological investigation was performed in order to characterize his immune status, and to distinguish between a primary immunodeficiency and a side effect of Rituximab treatment. We provide an extensive presentation and discussion of the literature on the basic immunology of CVID, the mechanism of action of Rituximab, and the immunopathogenesis of hypogammaglobulinemia observed in this patient. We suggest that CVID should be ruled out in any patient with immune cytopenias in order to avoid diagnostic delay. Likewise, we stress the importance of monitoring immunoglobulin levels before, during, and after Rituximab therapy to identify patients with hypogammaglobulinemia to ensure initiation of immunoglobulin replacement therapy in order to avoid life-threatening invasive bacterial infections. Recent reports indicate that Rituximab is not contra-indicated for the treatment of CVID-associated thrombocytopenia, however concomitant immunoglobulin substitution therapy is of fundamental importance to minimize the risk of infections. Therefore, lessons can be learned from this case report by clinicians caring for patients with immunodeficiencies, haematological diseases or other autoimmune disorders, particularly, when Rituximab treatment may be considered.
Peripheral pancytopenia is not a disease by itself; rather it describes simultaneous presence of anemia, leucopenia and thrombocytopenia resulting from a number of disease processes. Only a few systematic studies have been published on the topic of pancytopenia, although extensive studies have been done for its different etiological factors like aplastic anemia, megaloblastic anemia, leukemia, etc. Thus, this study was carried out to investigate for and to identify the causes of pancytopenia, to find out the frequency of different causes, to determine the incidence of pancytopenia in relation to sex and age and to compare our findings with those of other similar studies from this part of the world. This was a prospective study conducted in the Department of Pathology of a teaching institute and a tertiary care hospital in southern Maharashtra, India, over a period of two years. All the patients referred to the central clinical laboratory for routine complete blood count (CBC) and peripheral smear (PS) examination, from both - the outpatient and the inpatient departments, were screened for pancytopenia. Of these, a total number of 250 cases that fulfilled the diagnostic criteria were selected.Detailed hematological investigations followed by bone marrow aspiration wherever indicated and possible were performed according to standard methods to ascertain the causes of pancytopenia. A definite male preponderance was observed, the male to female ratio being 2.6 : 1. The majority of cases were encountered in 3rd and 4th decades. Hypersplenism (29.2%), Infections (25.6%), Myelosuppressants (16.8%) and Megaloblastosis (13.2%) were the four most common causes in this large series on pancytopenia from a single centre in India. Detailed clinical history and meticulous physical examination along with baseline hematological investigations, provides invaluable information in the complete workup of pancytopenic patients, helping in systematic planning of further investigations to diagnose and ascertain the cause, avoiding a battery of unnecessary tests.
Anaemia is a common complication of infection with the human immunodeficiency virus (HIV) and may have various causes. The aim of this study was to determine the prevalence and related factors of anemia in HAART-naive HIV positive Patients. A retrospective study was conducted on HAART naive HIV positive patients at the Gondar University Hospital between September 2011 and August 2012. Socio-demographic and immunohematological (hemoglobin and CD4+ T cells) data were collected carefully from the existing ART logbook and patient follow up cards. Anaemia was defined according to the WHO criteria. The overall prevalence of anaemia was 138 (35%). Female HAART naive HIV positive patients had significantly (P < 0.05) higher prevalence of anaemia than males (62% Vs 38%). The prevalence of anaemia at different CD4 level was; 6 (4%) with CD4 count greater than 500 cells/μL, 18 (13%) with a CD4 count of 350-500 cells/μL, 37 (27%) with a CD4 count of 200-349 cells/μL, 44 (32%) with a CD4 count of 100-199 cells/μL, 14 (10%) with a CD4 count of 50-99 and 19 (14%) with CD4 count of less than 50 cells/μL. Our findings showed that one-third of HAART naïve HIV positive patients were anaemic and the increase in prevalence of anaemia with decreased CD4 cell count was statistically significant. Therefore, early diagnosis and treatment of anaemia in these patients are essential.
Hematological abnormalities are a common complication of HIV infection. These abnormalities increase as the disease advances. Bone marrow abnormalities occur in all stages of HIV infection. Two hundred HIV infected individual were screened for hematological abnormalities from March 2007-March 2008. Absolute CD4 cell count analysis was carried out by flowcytometry. Depending on the results of the primary screening further investigations were performed, like iron studies, hemolytic work up, PNH work up and bone marrow evaluation. Other investigations included coagulation profile, urine analysis, blood culture (bacterial, fungal, mycobacterial), serology for Epstein Barr virus (EBV), Cytomegalovirus (CMV), Hepatitis B and C, and Parvo B19 infection. The most common hematological abnormality was anemia, seen in 65.5% (131/200) patients. Iron deficiency anemia was seen in 49.2% (/200) cases while anemia of chronic disease occurred in 50.7% (/200) cases. Bone marrow evaluation was carried out in 14 patients out of which staging marrow was performed in 2 cases of non-Hodgkin's lymphoma (NHL) and did not show any bone marrow infiltration. In remaining 12 cases bone marrow was done for evaluation of pancytopenia. Among patients with pancytopenia 50% (6/12) showed granulomas (4 were positive for AFB, 2 were positive for fungal cryptococci), 25% (3/12) showed hemophagocytosis. There was a strong negative correlation between anemia and CD4 counts in this study. Thrombocytopenia was seen in 7% (14/200) cases and had no significant correlation with CD4 counts. No patient had absolute neutrophil count (ANC) < 800 cells/microL. No case of coagulation abnormalities was found. Anemia in HIV patients can be a good clinical indicator to predict and access the underlying immune status. Patients should be investigated for hematological manifestations and appropriate steps should be taken to identify and treat the reversible factors.
There are many descriptions of the association of pica with iron deficiency in adults, but there are few reports in which observations available at diagnosis of iron deficiency were analyzed using multivariable techniques to identify significant predictors of pica. We sought to identify clinical and laboratory correlates of pica in adults with iron deficiency or depletion using univariable and stepwise forward logistic regression analyses. We reviewed charts of 262 non-pregnant adult outpatients (ages ≥18 y) who required treatment with intravenous iron dextran. We tabulated their sex, age, race/ethnicity, body mass index, symptoms and causes of iron deficiency or depletion, serum iron and complete blood count measures, and other conditions at diagnosis before intravenous iron dextran was administered. We excluded patients with serum creatinine >133 μmol/L or disorders that could affect erythrocyte or iron measures. Iron deficiency was defined as both SF <45 pmol/L and TS <10%. Iron depletion was defined as serum ferritin (SF) <112 pmol/L. We performed univariable comparisons and stepwise forward logistic regression analyses to identify significant correlates of pica. There were 230 women (184 white, 46 black; ages 19-91 y) and 32 men (31 white, 1 black; ages 24-81 y). 118 patients (45.0%) reported pica; of these, 87.3% reported ice pica (pagophagia). In univariable analyses, patients with pica had lower mean age, black race/ethnicity, and higher prevalences of cardiopulmonary and epithelial manifestations. The prevalence of iron deficiency, with or without anemia, did not differ significantly between patients with and without pica reports. Mean hemoglobin and mean corpuscular volume (MCV) were lower and mean red blood cell distribution width (RDW) and platelet count were higher in patients with pica. Thrombocytosis occurred only in women and was more prevalent in those with pica (20.4% vs. 8.3%; p = 0.0050). Mean total iron-binding capacity was higher and mean serum ferritin was lower in patients with pica. Nineteen patients developed a second episode of iron deficiency or depletion; concordance of recurrent pica (or absence of pica) was 95%. Predictors of pica in logistic regression analyses were age and MCV (negative associations; p = 0.0250 and 0.0018, respectively) and RDW and platelet count (positive associations; p = 0.0009 and 0.02215, respectively); the odds ratios of these predictors were low. In non-pregnant adult patients with iron deficiency or depletion, lower age is a significant predictor of pica. Patients with pica have lower MCV, higher RDW, and higher platelet counts than patients without pica.
The genetic polymorphism of thiopurine methyltransferase (TPMT) is well characterized in most populations. Four common polymorphic alleles are associated with impaired activity of the enzyme. These are TPMT*2 (238G>C), TPMT*3B (c.460G>A), TPMT*3A (c.460G>A and c.719A>G) and TPMT*3C (c.719A>G). The aim of the present study was to determine the frequency of TPMT polymorphisms and their association with the occurrence of adverse events, during 6-mercaptopurine therapy in pediatric acute lymphoblastic leukemic (ALL) patients in Gaza Strip. A total of 56 DNA samples from all pediatric ALL patients admitted to the pediatric hematology departments of Gaza strip hospitals were analyzed. Genomic DNA from peripheral blood leukocytes was isolated and the TPMT*2, TPMT*3B TPMT*3A and TPMT*3C allelic polymorphism was determined by PCR-RFLP and allele specific PCR technique. No TPMT*2, *3B or *3C alleles were detected. Only one, out of 56 patients, was found heterozygous for the TPMT*3A allele. Thus, the frequency of TPMT*3A allele was calculated to be 0.89%. Fourteen patients of ALL were suffering from myelotoxicity during 6-MP therapy. From our results, no significant association could be established between clinical and laboratory data and/or the presence of the mutation in TPMT gene. TPMT*3A was the only deficiency allele detected in our population with an allelic frequency of 0.89%. Other polymorphic alleles in TPMT gene, or factors other than TPMT polymorphisms may be responsible for the development of myelosuppression in cases that don't carry the investigated TPMT alleles (*2, *3A, *3B and *3C). Therefore, more studies are recommended to study such factors.
Background Benign neutropenia, i.e., neutropenia not associated with an increased risk of infection, may result in serious medical consequences when a 'standard' definition of neutropenia (absolute neutrophil count (ANC) & 1.5 A 10 super(9)cells/L) is universally applied to all races. The aims of this study were to determine the prevalence of benign neutropenia among healthy Arabs and evaluate its mode of inheritance. Methods ANCs were studied prospectively amongst a healthy indigenous population (n = 1032) from the United Arab Emirates undergoing a nation-wide sickle-cell and thalassemia screening program. The mean neutrophil count and the prevalence of benign neutropenia were compared by age, sex and amongst various tribes. Results The mean neutrophil count (A 10 super(9)cells/L) was 3.3 (range 0.95a7.6). Benign neutropenia was present in 110 (10.7%) subjects of whom 24 (2.3%) individuals had moderate neutropenia (ANC 0.5 a 1.0 A 10 super(9 )cells/L). In the 22 tribe-family groups, the prevalence of benign neutropenia varied between 0% and 38%. Benign neutropenia showed no difference in the frequency amongst the sexes (p = 0.23) and it was independent of age (Spearman's rho = 0.05, p = 0.13). The age-related mean neutrophil count was the lowest in Arabs when compared with other ethnic groups (Blacks, Europeans and Mexicans). The inheritance of benign neutropenia was consistent with an autosomal dominant pattern; however, the diversity of observed phenotypes suggested the presence of more than one genetic variant for this trait. Conclusion Arabs have a high prevalence of benign neutropenia that may be inherited as an autosomal dominant trait.
In Ethiopia, the existence of iron deficiency anemia is controversial despite the fact that Ethiopia is one of the least developed in Africa with a high burden of nutrient deficiencies. The first large nutrition study of a representative sample of women in Ethiopia was conducted from June to July 2005 and a systematically selected sub-sample of 970 of these subjects, 15 to 49 years old, were used in this analysis of nutritional anemia. Hemoglobin was measured from capillary blood using a portable HemoCue photometer. For serum ferritin, venous blood from antecubital veins was measured by an automated Elecsys 1020 using commercial kits. Diets were assessed via simplified food frequency questionnaire. The association of anemia to demographic and health variables was tested by chi-square and a stepwise backward logistic regression model was applied to test the significant associations observed in chi square tests. Mean hemoglobin +/- SD was 11.5 +/- 2.1 g/dL with a 29.4% prevalence of anemia. Mean serum ferritin was 58 +/- 41.1 ug/L with a 32.1% prevalence of iron deficiency. The overall prevalence rate of iron deficiency anemia was 18.0%. Prevalence of anemia, iron deficiency, and iron deficiency anemia was highest among those 31-49 years old (p < 0.05). Intake of vegetables less than once a day and meat less than once a week was common and was associated with increased anemia (p = 0.001). Although the prevalence of anemia was slightly higher among women with parasitic infestation the difference was not significant (p = 0.9). Nonetheless, anemia was significantly higher in women with history of illness and the association was retained even when the variable was adjusted for its confounding effect in the logistic regression models (AOR = 0.3; 95%CI = 0.17 to 0.5) signifying that the most probable causes of anemia is nutrition related and to some extent chronic illnesses. Moderate nutritional anemia in the form of iron deficiency anemia is a problem in Ethiopia and therefore, the need for improved supplementation to vulnerable groups is warranted to achieve the United Nation's Millennium Development Goals. Chronic illnesses are another important cause of anemia.
Anemia is a common problem in diabetic patients. Diabetic patients have a greater severity of anemia as the level of Glomerular Filtration Rate (GFR) decreases compared to non-diabetic patients. Despite these facts, anemia is unrecognized and largely untreated in patients with diabetes in Ethiopia particularly in those patients attending Fenote Selam Hospital. Therefore, this study was aimed to assess the association of anemia and renal function test among diabetes mellitus patients attending Fenote Selam Hospital, North West of Ethiopia. An Institutional -based cross-sectional study was conducted from February 2012 to April 2012 on diabetes mellitus (DM) patients. Systematic random sampling technique was used to get the total sample size of 384 patients. A total of seven ml of venous blood was collected from diabetes mellitus patients; two ml was collected by EDTA anticoagualted vacutainer test tube for haemoglobin determination and 5 ml venous blood was collected by plain vacutainer tube for creatinine and Blood urea nitrogen determination. The data were double entered and analyzed using SPSS-16 statistical software. The degree of association between independent and dependent variables was assessed using bivariate and multivariate logistic regression analysis in terms of P-value and odds ratio with 95% confidence interval. Out of the total 384 DM patients included in the study 73 (19%) were anemic. Fifty three (13.8%), forty eight (12.5%), and two hundred eighty three (73.7%) DM patients had an estimated GFR 90 ml/min/1.73 m respectively. One hundred eleven (28.9%) diabetic patients had increased urine albumin level. There was a statistically significant association between anaemia and Glomerular filtration rate (P<0.05) with Odds ratio of 8.58 and CI (10.21, 49.94). As the glomerular filtration rate increase, the risk to be anemic will decrease dramatically. The study showed that there was a significant association between anaemia and Glomerular filtration rate in DM patients. Therefore, DM patients should be strictly monitored for renal failure and anemia for proper management of diabetes patients.
Complete blood count (CBC) and reticulocyte (Retics) are routine hematology tests useful for the differential diagnosis of anemia and other medical conditions. However, it has been presumed that they are not used as regular as they should be in medical practice in Addis Ababa hospitals. A hospital-based cross-sectional questionnaire survey was conducted during November-December 2010, in which 408 clinicians participated and their response on the use of CBC and Retics was assessed. The always/frequently (A/F) response was considered to reflect routine use of the CBC/Retics parameters by the clinicians. The Chi square test was used to study statistical associations among different variables. Only four of 13 parameters in CBC were frequently or always used by more than 85% of the clinicians. Health Officers were observed to use 12 of the 13 CBC parameters less than the other professional group; interns and residents demonstrated highest use of CBC results. More than a third of clinicians' preferred white blood cell (WBC) differential report in percentages than the more useful absolute number report. Reticulocyte parameters were not being used by majority of clinicians in patient management. Clinicians rated 'average' regarding the adequacy of clinical laboratory methods course they took during medical education. As service users, clinicians indicated mm3 as unit of preference in cell count on the laboratory report form. Overall, most clinicians do not use much of the data provided on routine CBC report. Additional research is needed to understand the issue further. Responsible bodies should promote the appropriate use of CBC/Retics reports by clinicians.
Dan L. Longo is professor of medicine at Harvard Medical School in the division of hematology at Brigham and Women's Hospital and Deputy Editor of the New England Journal of Medicine. He is a Master of the American College of Physicians and is a member of the American Society of Clinical Investigation and the Association of American Physicians. He has been active in research on the treatment of malignant lymphoma including new treatments targeting CD30, CD40, HLA Class II molecules and immunoglobulin idiotype. His laboratory work has focused in part on the regulation of lymphocyte proliferation, NK cell effects on hematopoiesis, and tumor-induced immunosuppression. He is the Section Editor of the Malignant hematological diseases section for BMC Hematology. In this interview, he explains how he first became interested in hematology and gives his personal view on the recent progress and future challenges of the hematological cancer field in particular.
Congenital hemangiomas are benign abnormal proliferation of blood vessels. Noninvoluting congenital hemangiomas are a rare variant which persist, and may become bigger. Hemangiomas are known to be associated with thrombocytopenia, microangiopathic hemolytic anemia and Kasabach-Merritt phenomenon. Kasabach-Merritt phenomenon is characterized by consumptive coagulopathy with microangiopathic haemolyic anemia and thrombocytopenia. Platelet sequestration in the hemangioma or increased destruction which may either be immune or non immune are also further contributors to thrombocytopenia. A 45 year old female with a non involuting hemangioma and baseline thrombocytopenia was observed to develop repeated episodes of transient severe thrombocytopenia associated with a variety of infectious conditions. Laboratory investigations suggested a peripheral mechanism. Platelet counts always returned to baseline levels on resolution of the precipitating infection. The authors report this phenomenon as the first reported case of baseline thrombocytopenia complicated by recurrent episodes of transient severe thrombocytopenia following infections associated with a non involuting congenital hemangioma. The observations made in this patient were unique and hitherto unreported in medical literature. Both peripheral sequestration and destructive consumption were considered likely. Consumptive mechanisms were likely to encompass either or both immune and non immune causes. Further studies are needed to establish the precise pathogenesis.
This Editorial marks the launch of BMC Hematology, formerly known as BMC Blood Disorders, within the BMC series of journals published by BioMed Central. The scope of BMC Hematology encompasses basic, experimental and clinical research related to hematology. In this Editorial we will discuss the rationale behind this relaunch and how, as an open access journal providing unrestricted and free access to scientific and scholarly work, BMC Hematology will help disseminate research in the hematology field in a freely-accessible manner.
Glucose-6-Phosphate dehydrogenase (G6PD) is a key enzyme of the pentose monophosphate pathway, and its deficiency is the most common inherited enzymopathy worldwide. G6PD deficiency is common among Iraqis, including those of the Kurdish ethnic group, however no study of significance has ever addressed the molecular basis of this disorder in this population. The aim of this study is to determine the prevalence of this enzymopathy and its molecular basis among Iraqi Kurds. A total of 580 healthy male Kurdish Iraqis randomly selected from a main regional premarital screening center in Northern Iraq were screened for G6PD deficiency using methemoglobin reduction test. The results were confirmed by quantitative enzyme assay for the cases that showed G6PD deficiency. DNA analysis was performed on 115 G6PD deficient subjects, 50 from the premarital screening group and 65 unrelated Kurdish male patients with documented acute hemolytic episodes due to G6PD deficiency. Analysis was performed using polymerase chain reaction/restriction fragment length polymorphism for five deficient molecular variants, namely G6PD Mediterranean (563 C>T), G6PD Chatham (1003 G>A), G6PD A- (202 G>A), G6PD Aures (143 T>C) and G6PD Cosenza (1376 G>C), as well as the silent 1311 (C>T) mutation. Among 580 random Iraqi male Kurds, 63 (10.9%) had documented G6PD deficiency. Molecular studies performed on a total of 115 G6PD deficient males revealed that 101 (87.8%) had the G6PD Mediterranean variant and 10 (8.7%) had the G6PD Chatham variant. No cases of G6PD A-, G6PD Aures or G6PD Cosenza were identified, leaving 4 cases (3.5%) uncharacterized. Further molecular screening revealed that the silent mutation 1311 was present in 93/95 of the Mediterranean and 1/10 of the Chatham cases. The current study revealed a high prevalence of G6PD deficiency among Iraqi Kurdish population of Northern Iraq with most cases being due to the G6PD Mediterranean and Chatham variants. These results are similar to those reported from neighboring Iran and Turkey and to lesser extent other Mediterranean countries.
The first survey on sickle cell disease (SCD) done in Uganda in 1949, reported the district of Bundibugyo in Western Uganda to have the highest sickle cell trait (SCT) prevalence (45%). This is believed to be the highest in the whole world. According to the same survey, the prevalence of SCT in the districts of Mbale and Sironko in the East was 20-28%, whilst the districts of Mbarara and Ntungamo in the West had 1-5%. No follow-up surveys have been conducted over the past 60 years. SCA accounts for approximately 16.2% of all pediatric deaths in Uganda. The pattern of SCT inheritance, however, predicts likely changes in the prevalence and distribution of the SCT. The objective of the study therefore was to establish the current prevalence of the SCT in Uganda. This study was a cross sectional survey which was carried out in the districts of Mbale and Sironko in the Eastern, Mbarara/Ntungamo and Bundibugyo in Western Uganda. The participants were children (6 months-5 yrs). Blood was collected from each subject and analyzed for hemoglobin S using cellulose acetate Hb electrophoresis. The established prevalence of the SCT (As) in Eastern Uganda was 17.5% compared to 13.4% and 3% in Bundibugyo and Mbarara/Ntungamo respectively. 1.7% of the children in Eastern Uganda tested positive for haemoglobin ss relative to 3% in Bundibugyo, giving gene frequencies of 0.105 and 0.097 for the recessive gene respectively. No ss was detected in Mbarara/Ntungamo. A shift in the prevalence of the SCT and ss in Uganda is notable and may be explained by several biological and social factors. This study offers some evidence for the possible outcome of intermarriages in reducing the incidence of the SCT.