A systematic review of proteomic biomarkers associated with risk stratification in pediatric acute lymphoblastic leukemia

     Risk-based therapy protocols have dramatically improved survival rates in more than 80% of childhood acute lymphoblastic leukemia (chALL). Prognostic biomarkers could be valuable for predicting the relapsed ALL patients and may therefore contribute to improving ALL outcome. Presently, there are little data on the role of prognostic biomarkers in the risk stratification of ALL. The aim of the present systematic review is to survey the identified prognostic biomarkers of chALL. In this study, protein-protein interaction of identified biomarkers was evaluated to reveal the biological pathways related to high risk chALL. To pursue this goal, firstly all relevant studies were collected through the PubMed and Google Scholar databases with no restrictions. Then, the biomarkers of high risk patients were recorded and finally protein-protein interaction of biomarkers was analyzed through using the STRING database. After screening 82 abstracts, three studies were included with 36 high risk and 33 low risk B-ALL participants. Totally, 142 biomarkers were investigated in this study. Protein interaction network analysis of biomarkers revealed two main pathways, namely ribosome and spliceosome. Dysregulation of two key pathways, ribosome and spliceosome can be associated with the high risk phenotype of childhood acute lymphoblastic leukemia

Arg77His and Trp187Arg are the Most Common Mutations Causing FXIII Deficiency in Iran

The aim of this study was to review the literature for the genetic mutations causing inherited factoe XIII (FXIII) deficiency in patients from Iran, where the consanguineous marriage is common. Data were collected from 30 patients (18 males and 12 females) with FXIII deficiency, from 26 unrelated families. Data of mutation analysis were obtained from 2 previously published studies. A total of 7 mutations consisting of 5 new mutations and 2 previously reported mutations were identified. Of the 5 novel missense mutations, 2, Arg77His and Trp187Arg, were the most common in Iranian FXIII-deficient patients. In regions like Iran with high rate of consanguineous marriages, the identification of common mutations in disease like severe FXIII deficiency increases the capacity to make a precise screening and diagnosis assays to screen and diagnose families with high risk of FXIII deficiency for prevention of clinical complications in them

Assessment of Standard Operating Procedures (SOPs) Preparing Hygienic Condition in the Blood Donation Centers during the Outbreak of COVID-19

Background: The coronavirus disease 2019 (COVID-19) outbreak has led to an alteration in hygienic conditions. In this situation, improving standard operating procedures (SOPs) in blood donation centers is critical. The purpose of this study was the assessment of SOPs in the blood donation centers during the outbreak of COVID-19 by regular blood donors as external audits. Materials and Methods: Regular donors were selected as external inspectors in 31 provinces of Iran. The questionnaire containing 10 closed questions was provided to assess the hygienic SOPs of blood transfusion centers in the prevention of COVID-19 transmission. Comparison and evaluation of questionnaires were conducted by assigning an importance coefficient (IC)  score to each question. Results: Assessment of SOPs in blood donation departments by regular donors in 31 provinces of Iran showed that 18 centers (58.1%) received IC scores >10(Strong performance), 7 centers (22.6%) received the range of IC scores between7-10(acceptable performance), and 6 centers (19.4%) received IC scores <7(poor performance). The difference in IC scores between provinces was not statistically significant. Conclusion: This study confirms that the assessment of blood donation centers through regular blood donor inspection is a reliable method to identify the strengths and weaknesses of blood transfusion center services and ultimately leads to corrective intervention and improvement of hygienic SOPs to prevent COVID-19 transmission

Von Willebrand factor propeptide and pathophysiological mechanisms in European and Iranian patients with type 3 von Willebrand disease enrolled in the 3WINTERS-IPS study

Background Type 3 von Willebrand disease (VWD) is a severe bleeding disorder caused by the virtually complete absence of von Willebrand factor (VWF). Pathophysiological mechanisms of VWD like defective synthesis, secretion, and clearance of VWF have previously been evaluated using ratios of VWF propeptide (VWFpp) over VWF antigen (VWF:Ag) and factor (F)VIII coagulant activity (FVIII:C) over VWF:Ag. Objective To investigate whether the VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios may also be applied to understand the pathophysiological mechanism underlying type 3 VWD and whether VWFpp is associated with bleeding severity. Methods European and Iranian type 3 patients were enrolled in the 3WINTERS-IPS study. Plasma samples and buffy coats were collected and a bleeding assessment tool was administered at enrolment. VWF:Ag, VWFpp, FVIII:C, and genetic analyses were performed centrally, to confirm patients' diagnoses. VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios were compared among different variant classes using the Mann-Whitney test. Median differences with 95% confidence intervals (CI) were estimated using the Hodges-Lehmann method. VWFpp association with bleeding symptoms was assessed using Spearman's rank correlation. Results Homozygosity/compound heterozygosity for missense variants showed higher VWFpp level and VWFpp/VWF:Ag ratio than homozygosity/compound heterozygosity for null variants ([VWFpp median difference, 1.4 IU/dl; 95% CI, 0.2-2.7; P = .016]; [VWFpp/VWF:Ag median difference, 1.4; 95% CI, 0-4.2; P = .054]). FVIII:C/VWF:Ag ratio was similarly increased in both. VWFpp level did not correlate with the bleeding symptoms (r = .024; P = .778). Conclusions An increased VWFpp/VWF:Ag ratio is indicative of missense variants, whereas FVIII:C/VWF:Ag ratio does not discriminate missense from null alleles. The VWFpp level was not associated with the severity of bleeding phenotype.Peer reviewe

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

Successful Control of Massive Bleeding in a Child with Burkitt’s Lymphoma via a Biosimilar Recombinant Activated Factor VII (AryoSeven™)

We describe a case of a 4-year-old girl with Burkitt’s lymphoma, who suffered from a massive gastrointestinal hemorrhage 3 days after chemotherapy. In spite of applying the common practice in correction of coagulopathy, thrombocytopenia persisted and bleeding became life-threatening. In the present case report, we report a successful control of bleeding with a single-dose administration of a biosimilar recombinant activated human factor VII (AryoSeven)

Cardiac and renal malformations in a patient with sepsis and severe congenital neutropenia

Background: G6PC3 deficiency is a new neutropenic syndrome, which is characterized by severe persistent neutropenic, early onset infections and additional organ involvement, especially cardiac and urogenital malformations. Case Presentation: In this report, we present the clinical details of a recently known case of severe congenital neutropenic (SCN) with G6PC3 mutation, who experienced the first episode of infections at birth. Repeated absolute neutrophil count of less than 500/μl was detected during work-up of sepsis in the first month of life. SCN was diagnosed and granulocyte colony-stimulating factor (GCSF) administration initiated. Bone marrow examination revealed maturation arrest in myeloid series at promyelocyte-myelocyte stage. Diarrhea, bronchiolitis, and urinary tract infection were other infectious complications, while hydronephrosis, atrial septal defect, and patent ductus arteriosus were other manifestations. Conclusion: Prompt and accurate diagnosis of neutropenic patients and appropriate treatment can prevent further complications and improve the quality of life of the affected patients