Laboratory diagnosis for thalassemia intermedia: Are we there yet?

BACKGROUND: Differentiation between thalassemia major and thalassemia intermedia at presentation is not uniformly characterized, for which an absolute criteria needs to be developed. This study investigated the primary and secondary genetic modifiers to develop a laboratory finding by forming different genetic mutational combinations seen among thalassemia intermedia patients and comparing them with thalassemia major. METHODS: This cross-sectional study analyzed 315 thalassemia intermedia patients. One hundred and five thalassemia major patients were recruited on the basis of documented evidence of diagnosis and were receiving blood transfusion therapy regularly. Various mutational combinations were identified, and comparison was performed between thalassemia intermedia and major using statistical software STATA 11.1. RESULTS: The mean age of the total population was 5.9 ± 5.32 years of which 165 (52%) were males. Of the two groups (thalassemia intermedia and thalassemia major), IVSI-5, IVSI-1, and Fr 8-9 were more prevalent among the thalassemia intermedia cohort. When comparison was performed between the thalassemia intermedia and thalassemia major patients, it showed significant results for the presence of Xmn-1 polymorphism. CONCLUSION: The presence of IVSI-5 homozygous with Xmn-1, IVSI-5 heterozygous with Xmn-1, Cd 30 homozygous with or without Xmn-1 and IVSI-1 homozygous or heterozygous either with or without Xmn-1 prove to be strong indicators towards diagnosis of thalassemia intermedia.

Molecular epidemiology of ß-thalassemia in Pakistan: Far reaching implications.

BACKGROUND: ß -Thalassaemia, an autosomal recessive hemoglobinopathy, is one of the commonest genetically transmitted disorders throughout the world. Collective measures including carrier identification, genetic counseling and prenatal diagnosis are required for preventing ß-thalassemia. AIM: To achieve this objective, Identification of the spectrum of genetic mutations, especially for various ethnic backgrounds in Pakistan. Therefore, we designed a cross sectional prospective study to identify the frequency of various gene mutations in different ethnic groups of Pakistan. MATERIALS AND METHODS: Over a 5-year period, DNA from 648 blood samples {including specimens of chorionic villus sampling (CVS)} were analyzed for the twelve most common ß-thalassemia mutations found in the Pakistani population by a Multiplex amplification refractory mutation system (ARMS). Each sample was analyzed for the mutation as well as the normal gene, appropriate with negative and positive controls, and reagent blanks. RESULTS: Out of 648 samples mutations were identified in 640 (98.75%) samples by multiplex ARMS. 8 common ß-thalassemia mutations were identified in 8 different ethnic groups accounting for 93.9% of the ß-thalasemia alleles. CONCLUSIONS: Based on the outcome of this study a cost effective proposal is formulated for detection of ß-thalassemia mutations.

Evaluation of the combination therapy of hydroxyurea and thalidomide in ß-thalassemia.

Transfusion-related complications and lack of resources in low-to-middle-income countries have led to a search for novel therapies to reduce the need for blood transfusions in patients with ß-thalassemia. Hydroxyurea (HU) has demonstrated promising outcomes; additionally, thalidomide has also shown improvement in hemoglobin (Hb) levels for patients with ß-thalassemia in some studies. This study presents the findings of a single-arm nonrandomized trial to evaluate the efficacy of combination therapy of HU and thalidomide in children with ß-thalassemia. A total of 135 patients (median age, 6 [interquartile range, 3-10] years), 77 (57%) males and 58 (43%) females, were followed first using HU alone, for 6 months, and then using the combination of HU and thalidomide for another 6 months. The primary outcome was a response to therapy, as measured by the number of transfusions required and Hb levels, for patients while receiving HU alone and then while using the combination therapy. Study findings showed a significant decline in blood transfusion volume (P < .001) and a significant increase in median Hb levels within 3 and 6 months of the combination therapy (P < .001). Eighty-nine (65.93%) participants were good responders, 16 (11.85%) were responders, and 30 (22.22%) were nonresponders, whereas the responders had variable genetic mutations. A total of 38 adverse events were reported that resolved on supportive treatment or temporary hold of the intervention. The combination therapy demonstrated promising results and could be considered for a diverse patient population with ß-thalassemia. This trial was registered at www.clinicaltrials.gov as #NCT05132270.

Management of Anemia and other Hematologic Derangements in Patients with Chronic Kidney Disease.

INTRODUCTION: Chronic Kidney Disease (CKD) has adverse consequences on almost all body systems. The kidney does not function merely as an excretory organ, but participates in normal erythropoiesis, normal bone mineral deposition and blood pressure regulation. REVIEW: Anemia is prevalent in CKD with known deleterious effects on the car diovascular system. It is mostly due to erythropoietin deficiency, inhibition of erythropoiesis by uremic solutes, and reduction in red blood cell life span. Other possible causes include iron, B12 or folic acid deficiency or blood loss. Dysfunction of the endogenous erythropoietin is usually clinically evident once the glomerular filtration rate (GFR) falls below 20-25 ml/min. Treating anemia of CKD is based on correction of iron deficiency and replacement of decreased erythropoietin production by erythropoietin stimulating agents (ESA). Guidelines recommend targeting hemoglobin levels of no more than 10-12 g/dl since there is evidence of increased mortality and morbidity in patients with higher levels. Increased level of pro-coagulant biomarkers cause enhanced thrombotic activity in CKD patients which promotes ischemic cardiac events while platelet dysfunction leads to bleeding diathesis. If anticoagulation is indicated, low molecular weight heparins (LMWHs) offer certain advantage sbut the dosage needs to be adjusted with increasing grade of renal insufficiency. Antiplatelet agents are effective in averting shunt and catheter thrombosis, but not for avoiding the thrombosis of arteriovenous grafts. CONCLUSION: Health related quality of life in CKD patients can be improved by treating anemia. Newly available ESAs and the entry into the market of epoetinbiosimilars are expected to lead to improvements in the management of CKD and its complications.

Effect of Facebook on the life of Medical University students.

BACKGROUND: Facebook is a social networking service launched in February 2004, owned and operated by Facebook, Inc. As of June 2012, Facebook reports more than 1 billion active users. Objective of study was to evaluate the effect of Facebook on the social life, health and behavior of medical students. METHODOLOGY: It was a cross sectional, observational and questionnaire based study conducted in Dow University OF Health Sciences during the period of January 2012 to November 2012. We attempted to interview all the participants who could be approached during the period of the study. Participants were MBBS students, while all students of other courses and programs were taken as exclusion criteria. Approximately 1050 questionnaires were distributed to participants. Fifty questionnaires were rejected due to incomplete answers, yielding 1000 usable responses for an approximate 95% response rate. Informed verbal consent was taken from each participant. Study was ethically approved by Institutional Review Board of Dow University of Health Sciences. All the data was entered and analyzed through SPSS 19. RESULT: Out of total 1000 participants, males were 400 (40%) and females were 600 (60%). Participants were in the age group of 18-25 years with a mean age of 20.08 years. Most of the participants were using Facebook daily (N = 640, 64%) for around 3-4 hours (N = 401, 40.1%). Majority of them (N = 359, 35.9%) believed that they were equally active on Facebook and in real life while few believed their social life became worse after start using Facebook (N = 372, 37.2%). Most of the participants admitted that they were considered as shy in real world (N = 390, 39.0%) while in the world of Facebook they were considered as fun loving by their friends (N = 603, 60.3%). A large number of participants (N = 715, 75%) complained of mood swings. CONCLUSION: Youngsters are willing to compromise their health, social life, studies for the sake of fun and entertainment or whatever satisfaction they get after using Facebook. What we observed in our study was that although majority of our subjects showed multiple signs of Facebook addiction, they don't realize it and if even they realize it they don't want to quit Facebook and even if they want to quit, they can't. Our observance concluded that majority of the users are highly addicted.

Seropositivity of hepatitis C, hepatitis B and HIV in chronically transfused ß-thalassaemia major patients.

The purpose of this study was to determine the frequency and trend of transfusion transmitted infections (TTI) in chronically transfused ß-thalassaemia major (TM) patients with reference to the duration of transfusions. A cross-sectional study was done on 160 ß-TM patients and 5517 healthy blood donors to find out the prevalence of HCV, HBV and HIV infections. Out of 160 patients, 21 cases (13.1%) were anti-HCV positive, 2 (1.25%) were HBsAg positive. HIV antibodies were not detected in any sample. However, 109 (1.9%) and 104 (1.8%) of 5517 blood donors were positive for HCV and HBV respectively. No donor showed HIV antibodies. Anti-HCV was positive in 9/111(8.4%) thalassaemics (< 10 years of age) while 11/49 (22%) [> 10 years of age] showing significant difference (p = 0.005) among the two groups. For the past 10 - 12 years the screening of blood has reduced the magnitude of the disease significantly as shown by the trend in two age groups. Further improvements need to be done to implement uniform screening throughout the country.

Molecular epidemiology of ß-thalassemia in Pakistan: far reaching implications.

ß-thalassaemia, an autosomal recessive hemoglobinopathy, is one of the commonest genetically transmitted disorders throughout the world. Collective measures including carrier identification, genetic counseling and prenatal diagnosis are required for preventing ß-thalassemia. To achieve this objective, Identification of the spectrum of genetic mutations, especially for various ethnic backgrounds in Pakistan is necessary. Therefore, we designed a cross sectional prospective study to identify the frequency of various gene mutations in different ethnic groups of Pakistan. Over a 5-year period, DNA from 648 blood samples [including specimens of chorionic villus sampling (CVS)] were analyzed for the twelve most common ß-thalassemia mutations found in the Pakistani population by a Multiplex amplification refractory mutation system (ARMS). The most common mutation identified was Intervening Sequence 1-5 (IVS 1-5 (G-C)); accounting for 40.89% mutated alleles, and was represented in all ethnic groups. 15.7 % of the ß-thalassemia alleles were found to have Frameshift 8-9 (Fr 8-9) as the second most common mutation Other common genetic defects responsible for ß-thalassemia: IVS 1-1 (G-T) was found in 8.17%, Codon-30 (Cd-30 (G-C)) 8.02%, Codon-5(Cd-5 (-CT)) contributed 2.16% and Deletion 619 base pair (Del 619bp) affected 11.11% were found in Pakistan. This large study adds to the pre-existing data in Pakistan. Knowledge of the predominant mutation in a given ethnic group will not only help in developing a short panel of (population-specific) primers of mutations thereby providing a cost-effective method for prenatal diagnosis and also help the clinicians to counsel regarding blood transfusion regimen/ pregnancy termination.