Genetic Alterations, DNA Methylation, Alloantibodies and Phenotypic Heterogeneity in Type III von Willebrand Disease.

Type III von Willebrand disease is present in the Punjab province of Pakistan along with other inherited bleeding disorders like hemophilia. Cousin marriages are very common in Pakistan so genetic studies help to establish protocols for screening, especially at the antenatal level. Factors behind the phenotypic variation of the severity of bleeding in type III vWD are largely unknown. The study was conducted to determine Mutations/genetic alterations in type III von Willebrand disease and also to determine the association of different mutations, methylation status, ITGA2B/B3 mutations and alloimmunization with the severity of type III vWD. After informed consent and detailed history of the patients, routine tests and DNA extraction from blood, mutational analysis was performed by Next Generation Sequencing on Ion Torrent PGM. DNA methylation status was also checked with the help of PCR. In our cohort, 55 cases were detected with pathogenic mutations. A total of 27 different mutations were identified in 55 solved cases; 16 (59.2%) were novel. The mean bleeding score in truncating mutations and essential splice site mutations was relatively higher than weak and strong missense mutations. The mean bleeding score showed insignificant variation for different DNA methylation statuses of the VWF gene at the cg23551979 CpG site. Mutations in exons 7,10, 25, 28, 31, 43, and intron 41 splice site account for 75% of the mutations.

Malabsorption of iron as a cause of iron deficiency anemia in postmenopausal women.

OBJECTIVE: Malabsorption is one of the causes of iron deficiency anemia in postmenopausal women. The main objective of this study was to access the frequency of malabsorption in iron deficient anemic postmenopausal women. METHODS: A total of 123 postmenopausal women were enrolled in the study. Of these 123 women, 50 were included as 'control group' and 73 patients with comparable severity of anemia were the 'patient group'. Two tablets of ferrous sulfate (200 mg/tablet) along with one tablet of vitamin C (500 mg) were given to all participants. Serum iron levels were determined on samples collected from all participants before and after the administration of ferrous sulfate. Difference between before and after serum iron levels of normal and patients were compared. RESULTS: No change in serum iron between sample one and sample two represented malabsorption. Out of 73, 5 postmenopausal anemic patients showed no change in their serum iron level after the administration of ferrous sulfate. This study shows that frequency of malabsorption of iron in postmenopausal women is 6.8%. CONCLUSION: Malabsorption should be considered as a prevalent cause of iron deficiency anemia in postmenopausal women. It should be properly diagnosed and iron response should be monitored properly in postmenopausal women with IDA after oral iron therapy. If a postmenopausal woman does not show any response to oral iron therapy, she should be evaluated for iron loss (blood loss and/or malabsorption). Intravenous route should be used for the administration of iron in these patients.

Comparative analysis of cellulose acetate hemoglobin electrophoresis and high performance liquid chromatography for quantitative determination of hemoglobin A2.

BACKGROUND: The present study is designed to evaluate the reliability and cost effectiveness of cellulose acetate Hb electrophoresis and high performance liquid chromatography (HPLC) in the determination of HbA2 levels. METHODS: The test population comprised 160 individuals divided into four groups: normal individuals, ß-thalassemia trait (BTT) patients, iron deficiency anemia (IDA) patients, and co-morbid patients (BTT with IDA). HbA2 levels determined using cellulose acetate Hb electrophoresis and HPLC were compared. RESULTS: HbA2 levels were found to be diagnostic for classical BTT using either method. In co-morbid cases, both techniques failed to diagnose all cases of BTT. The sensitivity, specificity, and Youden's index for detection of the co-morbid condition was 69% and 66% for HPLC and cellulose acetate Hb electrophoresis, respectively. CONCLUSION: This study revealed that semi-automated cellulose acetate Hb electrophoresis is more suitable for use in ß-thalassemia prevention programs in low-income countries like Pakistan. This technique is easily available, simple and cost effective.

Disorders associated with malabsorption of iron: A critical review.

Malabsorption is a disorder of the gastrointestinal tract that leads to defective digestion, absorption and transport of important nutrients across the intestinal wall. Small intestine is the major site where most of the nutrients are absorbed. There are three main mechanisms of malabsorption; premucosal, mucosal and postmucosal. Premucosal malabsorption is the inadequate digestion due to improper mixing of gastrointestinal enzymes and bile with chyme. This could be because of surgical resection of the small intestine or a congenital deficiency of the enzymes and bile responsible for digestion e.g. postgastrectomy, chronic pancreatitis, pancreatic cancer, cystic fibrosis, gallstones, cholangitis etc. Mucosal malabsorption occurs in celiac disease, tropical sprue, Crohn's disease etc. Postmucosal condition arises due to impaired nutrients transport e.g. intestinal lymphangiectasia, macroglobulinemia etc. Disorders of malabsorption lead to decreased iron absorption and produce iron deficiency anemia. Using the index terms malabsorption, postgastrectomy, chronic pancreatitis, pancreatic cancer, cystic fibrosis, gallstones, cholangitis, celiac disease, tropical sprue, Crohn's disease intestinal lymphangiectasia, macroglobulinemia and iron deficiency anemia the MEDLINE and EMBASE databases were searched. Additional data sources included bibliographies and references of identified articles.

PAH exposure and oxidative stress indicators of human cohorts exposed to traffic pollution in Lahore city (Pakistan).

Pollution from road traffic is not only a major source of exposure to polycyclic aromatic hydrocarbons (PAHs) but also a growing problem in the city of Lahore (Pakistan). In this study, we evaluated exposure to traffic-related PAHs, among subjects including traffic police officers (TPs), rickshaw drivers (RKs) shopkeepers working near main roads (SKs) and a control group (CN) for comparative analyses. We monitored the 1-hydroxypyrene (1-OHP) as biomarkers of exposure to PAHs and its probable association with catalase (CAT), glutathione (GSH) glutathione peroxidase (GSHPx) activity as biomarkers of oxidative stress in selected cohorts from the city Lahore. Results showed that median 1-OHP concentration was significantly higher in TPs than CN (med 1.21 vs. 0.51 µmol mol-C(-1) respectively, P=0.046), followed by RKs (0.68 µmol mol-C(-1), P=0.19 vs. CN). Furthermore, GSH, GSHPx, and CAT activities were also higher in exposed subjects than CN, which indicated that they experienced oxidative stress. Similar, but less severe observations were recorded in SKs. Observation of self-reported health status showed that, on the basis of daily time spent in the middle of heavy traffic, TPs and RKs most frequently suffered from adverse head and respiratory symptoms. The study shows that increasing traffic pollution can be associated with important health risk factor not only for the workers in transport industry but also for the public. Finally, the issue of traffic pollution in Lahore city needs to be addressed on priority.

Frequency of ABH secretors and non secretors: A cross sectional study in Karachi.

OBJECTIVE: ABO blood group and secretor status is valuable in relation to some diseases in clinical and forensic medicine. Across the globe there are geographic and racial differences in the frequency of secretors and non-secretors. Aim of this study was to evaluate the status of ABH blood group secretors and non-secretors in Karachi (Pakistan). METHODS: Blood and saliva samples were randomly collected from one hundred and one (n=101) healthy adult students (76 male, 25 female) ranging in age from 15 to 40 years. Their ABO and Rhesus blood groups were determined by conventional methods, and their secretor status was studied by hemagglutination inhibition method of saliva. RESULTS: RESULTS showed that 64.4% of the study population were ABH blood group secretors while 35.6% were non-secretors. Frequencies of the secretor status among various ABO blood groups were 71.4% in group A, 79.5% in group B, 45.5% in group AB, and 61.5% in group O. CONCLUSION: Frequency of ABH secretor is high (64.4%). Blood group B has the highest secretor (79.5%) frequency while Blood group AB has the lowest (45.5%).