79 research outputs found
missense mutation (A300P) causing pyruvate kinase deficiency in an Omani Kindred—PK deficiency masquerading as congenital dyserythropoietic anemia
No full text: We report herein a child with transfusion-dependent chronic anemia, the cause of which was difficult to establish because of his transfusion dependency. The clinical and laboratory features suggested a chronic nonspherocytic hemolytic anemia (CNSHA) with bone marrow features suggestive of congenital dyserythropoietic anemia (CDA). DNA studies, however, revealed the underlying condition to be due to a novel mutation in the PKLR gene responsible for pyruvate kinase deficiency (PKD). Molecular investigations by a targeted next-generation sequencing (t-NGS) using a custom panel of 71 genes involved in the red blood cell (RBC) disorders revealed that the patient was homozygous for a novel missense mutation c.898G>C, p.Ala300Pro, whereas both his parents were heterozygous for the same mutation
Deferasirox (Exjade®) significantly improves cardiac T2* in heavily iron-overloaded patients with β-thalassemia major
No full textNoninvasive measurement of tissue iron levels can be assessed using T2* magnetic resonance imaging (MRI) to identify and monitor patients with iron overload. This study monitored cardiac siderosis using T2* MRI in a cohort of 19 heavily iron-overloaded patients with β-thalassemia major receiving iron chelation therapy with deferasirox over an 18-month period. Overall, deferasirox therapy significantly improved mean ± standard deviation cardiac T2* from a baseline of 17.2±10.8 to 21.5±12.8 ms (+25.0percent; P=0.02). A concomitant reduction in median serum ferritin from a baseline of 5,497 to 4,235 ng-mL (-23.0percent; P=0.001), and mean liver iron concentration from 24.2±9.0 to 17.6± 12.9 mg Fe-g dry weight (-27.1percent; P=0.01) was also seen. Improvements were seen in patients with various degrees of cardiac siderosis, including those patients with a baseline cardiac T2* of 10 ms, indicative of high cardiac iron burden. These findings therefore support previous observations that deferasirox is effective in the removal of myocardial iron with concomitant reduction in total body iron. © The Author(s) 2009.Anderson LJ, 2006, ACTA HAEMATOL-BASEL, V115, P106, DOI 10.1159-000089475; Anderson LJ, 2001, EUR HEART J, V22, P2171, DOI 10.1053-euhj.2001.2822; Borgna-Pignatti C, 2004, HAEMATOLOGICA, V89, P1187; BRITTENHAM GM, 1994, NEW ENGL J MED, V331, P567, DOI 10.1056-NEJM199409013310902; Cappellini MD, 2006, BLOOD, V107, P3455, DOI 10.1182-blood-2005-08-3430; Daar S, 2009, HAEMATOL-HEMATOL J, V94, P140, DOI 10.3324-haematol.13845; ELEFTHERIOU P, 2006, HAEMATOLOGICA S1, V91, P999; Garbowski M, 2008, BLOOD, V112, P116; Kolnagou A, 2006, HEMOGLOBIN, V30, P219, DOI 10.1080-03630260600642542; Noetzli LJ, 2008, BLOOD, V112, P2973, DOI 10.1182-blood-2008-04-148767; PENNELL D, 2008, BLOOD, V112, P3874; Pennell DJ, 2008, BLOOD, V112, P3873; Porter J, 2008, EUR J HAEMATOL, V80, P168, DOI 10.1111-j.1600-0609.2007.00985.x; St Pierre TG, 2005, BLOOD, V105, P855, DOI 10.1182-blood-2004-01-0177; Taher A, 2009, EUR J HAEMATOL, V82, P458, DOI 10.1111-j.1600-0609.2009.01228.x; Vichinsky E, 2007, BRIT J HAEMATOL, V136, P501, DOI 10.1111-j.1365-2141.2006.06455.x; Westwood M, 2003, J MAGN RESON IMAGING, V18, P33, DOI 10.1002-jmri.10332; Wood JC, 2004, BLOOD, V104, p111A; Wood JC, 2008, BLOOD, V112, P3882; Wood JC, 2006, TRANSL RES, V148, P272, DOI 10.1016-j.trsl.2006.05.005; ZURLO MG, 1989, LANCET, V2, P2719222
COMPARISON OF METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS IN HEALTHY COMMUNITY HOSPITAL VISITORS[CA-MRSA] AND HOSPITAL STAFF [HA-MRSA]
Get PDFBackground: The prevalence of community associated methicillin resistant Staphylococcus aureus [CA-MRSA] in unknown in Oman.
Methods: Nasal and cell phones swabs were collected from hospital visitors and health-care workers on sterile polyester swabs and directly inoculated onto a mannitol salt agar containing oxacillin, allowing growth of methicillin-resistant microorganisms. Antibiotic susceptibility tests were performed using Kirby Bauer’s disc diffusion method on the isolates. A brief survey questionnaire was requested be filled to ascertain the exposure to known risk factors for CA-MRSA carriage.
Results: Overall, nasal colonization with CA-MRSA was seen in 34 individuals (18%, 95% confidence interval [CI] =12.5%-23.5%), whereas, CA-MRSA was additionally isolated from the cell phone surface in 12 participants (6.3%, 95% CI =5.6%-6.98%). Nasal colonization prevalence with HA-MRSA was seen in 16 individuals (13.8%, 95% confidence interval [CI] =7.5%-20.06%), whereas, HA-MRSA was additionally isolated from the cell phone surface in 3 participants (2.6%, 95% CI =1.7-4.54). Antibiotic sensitivity was 100% to linezolid and rifampicin in the CA-MRSA isolates. Antibiotic resistance to vancomycin and clindamycin varied between 9-11 % in the CA-MRSA isolates. There was no statistically significant correlation between CA-MRSA nasal carriage and the risk factors (P>0.05, Chi-square test).
Conclusions: The prevalence of CA-MRSA in the healthy community hospital visitors was 18 % (95% CI, 12.5% to 23.5%) as compared to 13.8% [HA-MRSA] in the hospital health-care staff. In spite of a significant prevalence of CA-MRSA, these strains were mostly sensitive. Recommendation the universal techniques of hand washing, personal hygiene and sanitation are thus warranted
ALLOIMMUNIZATION IN PATIENTS WITH SICKLE CELL DISEASE AND THALASSAEMIA: EXPERIENCE OF SINGLE CENTRE FROM OMAN
Get PDFBackground: Blood transfusion is an integral part of the supportive care for patients with sickle cell anemia and thalassaemia. The hazard of red cell alloimmunization, however, is one of the main complications of this therapy.
Objectives: The aim of this study was to evaluate the incidence of red cell alloimmunization in Omani patients with sickle cell anemia and thalassaemia.
Methods: This study included 262 patients whose historical transfusion records were available. One hundred and twenty-nine patients with thalassaemia who were attending the day care unit for regular transfusions, and 133 sickle cell anemia patients admitted at our hospital were included in this study. The Diamed gel system was used for the screening and identification of atypical antibodies.
Results: The rate of alloimmunization in sickle cell anemia patients was 31% (n=41), whereas in thalassaemia patients it was 20% (n=26). Antibodies to E, e, C, c, D, K, S, Fyª, Kpª, Jkª and Cw were observed. Among the two groups, 8 developed nonspecific antibodies, and 12 developed more than one antibody; however, 85% of patients were also immunized to Rh and Kell antigens.
Conclusions: Red cell transfusions are associated with a significant risk of alloimmunization. It is, therefore, imperative to perform an initial extended red cell phenotyping for both donors and recipients, and carefully select ABO, Rh and Kell matched donors
Necrotizing Enterocolitis in a Term Neonate Following Intravenous Immunoglobulin Therapy
No full textIMPACT OF MANNOSE-BINDING PROTEIN GENE POLYMORPHISMS IN OMANI SICKLE CELL DISEASE PATIENTS
Get PDFObjectives: Our objective was to study mannose binding protein (MBP) polymorphisms in exonic and promoter region and correlate associated infections and vasoocculsive (VOC) episodes, since MBP plays an important role in innate immunity by activating the complement system.
Methods: We studied the genetic polymorphisms in the Exon 1 (alleles A/O) and promoter region (alleles Y/X; H/L, P/Q) of the MBL2 gene, in sickle cell disease (SCD) patients as increased incidence of infections is seen in these patients. A PCR-based, targeted genomic DNA sequencing of MBL2 was used to study 68 SCD Omani patients and 44 controls (voluntary blood donors).
Results: The observed frequencies of MBL2 promoter polymorphism (-221, Y/X) were 44.4% and 20.5% for the heterozygous genotype Y/X and 3.2% and 2.2% for the homozygous (X/X) respectively between SCD patients and controls. MBL2 Exon1 gene mutations were 29.4% and 50% for the heterozygous genotype A/O and 5.9% and 6.8% respectively for the homozygous (O/O) genotype between SCD patients and controls. The distribution of variant MBL2 polymorphisms did not show any correlation in SCD patients with or without vasoocculsive crisis (VOC) attacks (p=0.162; OR-0.486; CI=0.177 -1.33), however, it was correlated with infections (p=0.0162; OR-3.55; CI 1.25-10.04).
Conclusions: Although the frequency of the genotypes and haplotypes of MBL2 in SCD patients did not differ from controls, overall in the SCD patient cohort the increased representation of variant alleles was significantly correlated with infections (p<0.05). However, these variant MBL2 polymorphisms did not seem to play a significant role in the VOC episodes in this SCD cohort.
Keywords: Mannose-binding lectin, polymorphism, promoter, Sickle cell disease, MBL2, MB
Reduction in labile plasma iron during treatment with deferasirox, a once-daily oral iron chelator, in heavily iron-overloaded patients with β-thalassaemia
No full textThis subgroup analysis evaluated the effect of once-daily oral deferasirox on labile plasma iron (LPI) levels in patients from the prospective, 1-yr, multicentre ESCALATOR study. Mean baseline liver iron concentration and median serum ferritin levels were 28.6 ± 10.3 mg Fe-g dry weight and 6334 ng-mL respectively, indicating high iron burden despite prior chelation therapy. Baseline LPI levels (0.98 ± 0.82 μmol-L) decreased significantly to 0.12 ± 0.16 μmol-L, 2 h after first deferasirox dose (P = 0.0006). Reductions from pre- to post-deferasirox administration were also observed at all other time points. Compared to baseline, there was a significant reduction in preadministration LPI that reached the normal range at week 4 and throughout the remainder of the study (P ≤ 0.02). Pharmacokinetic analysis demonstrated an inverse relationship between preadministration LPI levels and trough deferasirox plasma concentrations. Once-daily dosing with deferasirox ≥20 mg-kg-d provided sustained reduction in LPI levels in these heavily iron-overloaded patients, suggesting 24-h protection from LPI. Deferasirox may therefore reduce unregulated tissue iron loading and prevent further end-organ damage. © 2009 Blackwell Munksgaard.ALREFAIE FN, 1995, BRIT J HAEMATOL, V89, P403, DOI 10.1111-j.1365-2141.1995.tb03318.x; Breuer W, 2000, TRANSFUS SCI, V23, P185, DOI 10.1016-S0955-3886(00)00087-4; Cabantchik ZI, 2005, BEST PRACT RES CL HA, V18, P277, DOI 10.1016-j.beha.2004.10.003; Esposito BP, 2003, BLOOD, V102, P2670, DOI 10.1182-blood-2003-03-0807; HERSHKO C, 1978, BRIT J HAEMATOL, V40, P255, DOI 10.1111-j.1365-2141.1978.tb03662.x; Nisbet-Brown E, 2003, LANCET, V361, P1597, DOI 10.1016-S0140-6736(03)13309-0; OLIVIERI NF, 1994, NEW ENGL J MED, V331, P574, DOI 10.1056-NEJM199409013310903; Olivieri NF, 1997, BLOOD, V89, P739; Piga A, 2006, HAEMATOL-HEMATOL J, V91, P873; Porter JB, 2001, SEMIN HEMATOL, V38, P63, DOI 10.1053-shem.2001.2014537353
INCREASED VASOOCCLUSIVE CRISIS IN “O” BLOOD GROUP SICKLE CELL DISEASE PATIENTS: ASSOCIATION WITH UNDERLYING THROMBOSPONDIN LEVELS.
Get PDFAbstract:
Objectives: To explore the incidence of vaso-occlusive crisis (VOC) in Blood Group “O” sickle cell disease (SCD) patients, and correlate it with the blood group and thrombospondin (TSP) levels.
Methods: In 89 consecutive SCD patients, blood samples were obtained for vWF antigen, collagen binding activity, blood group typing, C-reactive protein, variant hemoglobin analysis (HPLC), Serum TSP 1 and TSP 2 levels, complete blood counts, liver function tests, LDH and renal function tests during VOC episodes and in steady state conditions.
Results: In the steady state SCD patients (n=72), “O” blood group patients (n=37) showed significantly higher median serum TSP 1 and TSP 2 levels than the non “O” blood group patients [n=35] [p <0.05, Mann-Whitney test], with an inverse relation between VWF:Ag, Factor VIII:C and TSP levels. Furthermore, the serum TSP 1 and TSP 2 levels were significantly higher in patients presenting with acute VOC [n=17], and in those with repeated VOC’s (group 1, n=16) especially amongst those patients with blood group “O” [p, <0.05, Mann-Whitney test].
Conclusions: The study shows that there was an inverse relation between TSP and vWF levels, in blood group “O” SCD patients with an upregulation of the TSP levels. Expectedly, during active VOC crisis, the TSP 1 and TSP 2 levels were significantly elevated.
Key Words: VOC; SCD; TSP; vWD; Blood group
PREVALENCE OF HEPATITIS B, HEPATITIS C AND HIV IN MULTIPLY TRANSFUSED SICKLE CELL DISEASE PATIENTS FROM OMAN
Get PDFBackground: In Oman, the prevalence of hepatitis B (HBV) infection is 5.8% with 2.8–7.1% HBV carriers. Hepatitis C (HCV) prevalence amongst Omanis is 0.41%. A total of 2917 human immunodeficiency virus (HIV) infections were notified amongst Omanis by 2017. This study was performed as there was no data on the prevalence of HIV, HBV and HCV in sickle cell disease (SCD) patients from Oman.
Study Design and Methods: In this retrospective, cross-sectional study, medical records of all SCD patients who attended our hospital between 2011 to 2017 were retrieved from the hospital information system. Following approval by the local medical research and ethics committee, data on HIV, HBV and HCV exposure were recorded to estimate the prevalence.
Results: Amongst a total of 1000 SCD patients (491 males and 509 females), twenty-three (2.3%) patients showed positive serology for hepatitis B surface antigen (HbsAg), of whom sixteen (1.6%) were HBV DNA positive. 126 (12.6%) had anti-HCV antibodies (anti-HCV), of whom fifty-two (5.2%) were HCV RNA positive. None of the patients had positive serology for HIV. A normal liver was observed on abdominal ultrasound in 788 (78.8%) patients, whereas, 208 (20.8%) had hepatomegaly and 4 (0.4%) had liver cirrhosis. Thirty-six (3.6%) patients died, but in only two patients, the mortality was due to cirrhosis of the liver.
Conclusion: This study provides the first comprehensive data on the prevalence of HBV and HCV infections among Omani SCD patients exposed to blood transfusions. Reassuringly, no case with HIV was observed.
Keywords: Prevalence; Hepatitis; HBV; HCV; HIV; infectio
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