Bleeding symptoms in patients diagnosed as type 3 von Willebrand disease : Results from 3WINTERS-IPS, an international and collaborative cross-sectional study

Background Type 3 von Willebrand's disease (VWD) patients present markedly reduced levels of von Willebrand factor and factor VIII. Because of its rarity, the bleeding phenotype of type 3 VWD is poorly described, as compared to type 1 VWD. Aims To evaluate the frequency and the severity of bleeding symptoms across age and sex groups in type 3 patients and to compare these with those observed in type 1 VWD patients to investigate any possible clustering of bleeding symptoms within type 3 patients. Methods We compared the bleeding phenotype and computed the bleeding score (BS) using the MCMDM-1VWD bleeding questionnaire in patients enrolled in the 3WINTERS-IPS and MCMDM-1VWD studies. Results In 223 unrelated type 3 VWD patients, both the BS and the number of clinically relevant bleeding symptoms were increased in type 3 as compared to type 1 VWD patients (15 versus 6 and 5 versus 3). Intracranial bleeding, oral cavity, hemarthroses, and deep hematomas were at least five-fold over-represented in type 3 VWD. A more severe bleeding phenotype was evident in patients having von Willebrand factor antigen levels <20 IU/dL at diagnosis in the two merged cohorts. In type 3 patients, there was an apparent clustering of hemarthrosis with gastrointestinal bleeding and epistaxis, whereas bleeding after surgery or tooth extraction clusters with oral bleeding and menorrhagia. Conclusions In the largest cohort of type 3 VWD patients, we were able to describe a distinct clinical phenotype that is associated with the presence of a more severe hemostatic defect.Peer reviewe

Correlation between blood lead concentration and iron deficiency in Iranian children

Background: Iron deficiency anaemia is the most common nutritional anaemia among children. Lead toxicity is a serious health threat, especially in developing countries due to environmental pollution. It was thus aimed to investigate correlation between blood lead concentration and iron deficiency in children of Mashhad, Iran. Materials and Methods: This cross sectional study was performed on children between 1 year and 10 years, in Imam Reza teaching hospital of Mashhad, Iran, in 2010. Indeed during complete blood count (CBC), we measured iron and total iron binding capacity (TIBC) by colorimetric methods, ferritin by radioimmune assay and blood lead concentration by atomic absorption method. Results were analysed by Statistical Package for Social Sciences (SPSS) (version 11.5), using statistical tests including independent sample t-test, Mann-Whitney U test, Spearman′s test and analysis of variance (ANOVA) and Pearson′s or Spearman′s correlation coefficient. P value ≤ 0.05 was considered as a significant level. Results: We studied 223 cases including 98 control children and 125 patients. All children had lead intoxication. Mean (±SD) blood lead concentration in the control group was 57.1 ± 25.3 (ranged 20-212) μg/dl and in the patient group was 57 ± 20.4 (ranged 10.9-159) μg/dl with no significant difference (P value = 0.713). We also did not find any correlation between blood lead concentration and haemoglobin, ferritin, iron, TIBC, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), white blood cells (WBC) and platelets. Conclusion: Based on these results, no correlation was found between blood lead concentration and iron deficiency in the children. Because all children had lead intoxication, further studies in highly polluted and a comparison with a low polluted area are necessary to make a general conclusion

Reviews in Clinical Medicine Comparison of dexamethasone and anti-D immune globulin for immune thrombocytopenia purpura in children ARTICLE INFO ABSTRACT

Keywords Children Dexamethasone Immune thrombocytopenic purpura (ITP) Different therapeutic options in children with immune thrombocytopenic purpura include observation alone, periodic treatment with corticosteroids, intravenous immunoglobulin (IVIG) or anti-D, chronic administration of immunosuppressive agents, and splenectomy. Preference of the type of therapy depends on the degree of thrombocytopenia and clinical bleeding manifestations. Dexamethasone is safe but its side effects are the main disadvantages for its usage. Anti-D is more expensive than dexamethason but the side effect is rare and not dangerous and response to treatment is assessed in approximately 3 days after infusion

Use of restriction fragment length polymorphism to identify Candida species, related to onychomycosis

Background: Onychomycosis is one of the most common clinical forms of fungal infections due to both filamentous fungi and yeasts. The genus of Candida is one of the most prominent causes of onychomycosis in all around the world. Although Candida albicans is still the most frequent cause of nail infections, use of broad-spectrum antifungal agents has led to a shift in the etiology of C. albicans to non-albicans species. The aim of the present study is rapid and precise identification of candida species isolated from nail infection by using of PCR-RFLP technique. Materials and Methods: A total of 360 clinical yeast strains were collected from nail infections in Iran. Genomic DNA was extracted using FTA; cards. ITS1-5.8SrDNA-ITS2 region was amplified using universal primers and subsequently products were digested with the restriction enzyme MspI. For identification of newly described species (C. parapsilosis complex), the SADH gene was amplified, followed by digestion with Nla III restriction enzyme. Results: Candida albicans was the most commonly isolated species (41.1%), followed by C. parapsilosis (21.4%), C. tropicalis (12.8%), C. kefyr (9.4%), C. krusei (5.5%), C. orthopsilosis (4.1%), C. glabrata (2.8%), C. guilliermondii (1.4%), C. rugosa (0.8%), and C. lusitaniae (0.5%). Patients in the age groups of 51-60 and 81-90 years had the highest and lowest distribution of positive specimens, respectively. Conclusion: Rapid and precise identification of Candida species from clinical specimens lead to appropriate therapeutic plans

Susceptibility pattern of Candida albicans isolated from Iranian patients to antifungal agents

Background and Purpose: Candidiasis is a major fungal infection, and Candida albicans is the major cause of infections in humans. The Clinical and Laboratory Standards Institute (CLSI) developed new breakpoints for antifungal agents against C. albicans. In this multi-center study, we aimed to determine the drug susceptibility profile of C. albicans, isolated from Iranian population according to new species-specific CLSI. Materials and Methods: Clinical samples were cultured on Sabouraud dextrose agar and were incubated at room temperature for seven days. The isolates were transferred to Professor Alborzi Clinical Microbiology Research Center, Shiraz, Iran. C. albicans were identified by using API 20C AUX system. Broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of amphotericin B, caspofungin, voriconazole, fluconazole, posaconazole, itraconazole, and ketoconazole, based on CLSI document M27-S4 and new breakpoints for some azoles and caspofungin. Results: Overall, 397 C. albicans were isolated from patients admitted to ten university hospitals in Iran. The MIC90 of the isolates to amphotericin B, caspofungin, voriconazole, fluconazole, posaconazole, itraconazole, and ketoconazole were 0.125, 0.125, 0.125, 1, 0.064, 0.5, and 0.125 &mu;g/ml, and rates of resistance were 0.5%, 0.3%, 3.8%, 2.8%, and 2.5% for amphotericin B, caspofungin, voriconazole, fluconazole, and itraconazole, respectively. Conclusion: According to our data, fluconazole is the drug of choice for management of patients at risk for systemic candidiasis throughout the region, since it is cost-effective with low side effects

YEAST PANEL multiplex PCR for identification of clinically important yeast species: stepwise diagnostic strategy, useful for developing countries

Identification of opportunistic yeasts in developing countries is mainly performed by phenotypic assays, which are time-consuming and prone to errors. Wrong species identification may result in suboptimal treatment and inaccurate epidemiological data. To improve rapidity and accuracy of species identification, a diagnostic strategy using a stepwise "YEAST PANEL multiplex PCR assays" targeting 21 clinically important yeast species of Candida, Trichosporon, Rhodotorula, Cryptococcus, and Geotrichum was designed. Four hundred CBS reference strains were used for optimization and specificity testing. Eight hundred clinical species were prepared in blinded sets for multiplex polymerase chain reaction (PCR) and matrix-assisted laser desorption time of flight mass spectrophotometry (MALDI-TOF MS) investigation. Results obtained from YEAST PANEL multiplex PCR assay were 100% consistent with those of MALDI-TOF MS. Utilization of pure colony testing showed distinct amplicons for each species, thus eliminating the need for DNA extraction. The targeted yeast species of this assay are responsible for 95% of the yeast infections. In conclusion, due to the high accuracy and coverage of a broad range of yeasts, this assay could be useful for identification in routine laboratories and epidemiological studies

Genotypes of European and Iranian patients with type 3 von Willebrand disease enrolled in 3WINTERS-IPS

Type 3 von Willebrand disease (VWD3) is a rare and severe bleeding disorder characterized by often undetectable von Willebrand factor (VWF) plasma levels, a recessive inheritance pattern, and heterogeneous genotype. The objective of this study was to identify the VWF defects in 265 European and Iranian patients with VWD3 enrolled in 3WINTERS-IPS (Type 3 Von Willebrand International Registries Inhibitor Prospective Study). All analyses were performed in centralized laboratories. The VWF genotype was studied in 231 patients with available DNA (121 [115 families] from Europe [EU], and 110 [91 families] from Iran [IR]). Among 206 unrelated patients, 134 were homozygous (EU/IR 5 57/77) and 50 were compound heterozygous (EU/IR 5 43/7) for VWF variants. In 22 patients, no or only one variant was found. A total of 154 different VWF variants (EU/IR 5 101/58 [5 shared]) were identified among the 379 affected alleles (EU/IR 5 210/169), of which 48 (EU/IR 5 18/30) were novel. The variants p.Arg1659*, p.Arg1853*, p.Arg2535*, p.Cys275Ser, and delEx1_Ex5 were found in both European and Iranian VWD3 patients. Sixty variants were identified only in a single allele (EU/IR 5 50/10), whereas 18 were recurrent ($3 patients) within 144 affected alleles. Nine large deletions and one large insertion were found. Although most variants predicted null alleles, 21% of patients carried at least 1 missense variant. VWD3 genotype was more heterogeneous in the European population than in the Iranian population, with nearly twice as many different variants. A higher number of novel variants were found in the Iranian VWD3 patients