Correlation of del13q, del11q and Trisomy 12 with Laboratory and Clinical Features of Chronic Lymphocytic Leukemia in Iranian Patients

Background: There is a strong association between chromosomal abnormalities and laboratory features and clinical course of the B-cell chronic lymphocytic leukemia (B-CLL). The aim of this study was to investigate the frequency and correlation of cytogenetic aberrations with laboratory and clinical features of the disease. Methods: Clinical and laboratory features of 65 CLL patients were collected from their hospital profiles and their blood and/or bone marrow were examined by conventional cytogenetics and interphase FISH methods. Results: Conventional cytogenetic methods identified 27.7% chromosomal abnormalities in 65 patients. I-FISH analysis for del13q, del11q and trisomy 12 revealed abnormality in 75.4% of patients. The results showed that IFISH improved the detection rate of chromosomal abnormalities and it enhanced detection. Statistical analysis was performed on sex, age, family history, Rai stage and CD markers on trisomy 12, del 11q and del 13q subgroups. There was a high frequency of Ray stages I and II within del13q subgroup, Rai stages III and IV within del11q subgroup and Rai stage II within trisomy 12 subgroup. Mean of CD38 in patients with del 11q was significantly higher than mean of patients with trisomy 12 and del 13q. Conclusion: High level of CD38 and presence of del11q indicated a poor prognosis and low level of CD38 and presence of del13q was indicative of good prognosis in Iranian B-CLL patients. Trisomy 12 had an intermediate prognostic value

Identification of the First Iranian Family with “γArg275Cys” Mutation (Fibrinogen Tokyo II)

Background: Inherited fibrinogen deficiencies areclassified into two categories: quantitative, including afibrinogenemia and hypofibrinogenemia and qualitative, including dysfibrinogenemia. Any mutation in fibrinogen genes accounts for one of these disorders.Case report: This article reports an Iranian family with dysfibrinogenemia without any clinical signs accidentally diagnosed by routine coagulation tests with slightly elevated PT and APTT a few years ago. Fordeterminationof disease causing genetic aberration in fibrinogen genes, DNA sequencing of three hot spots of these genes (i.e. exon 2 of FGA,exon 2 of FGB and exon 8 of FGG)was performed. Analysis of sequencing results revealed a heterozygous missense mutation c.901 C>T (Arg275Cys) in exon 8 of FGG in mother and children.No mutationwas detected in father’s sample.Fibrinogen with this mutation is known as Tokyo II.Conclusion: γArg275Cys is a heterozygous mutation that impairs the function of fibrinogen andhas been solely reported in dysfibrinogenemic patients. Clinical findings in this family (no history of bleeding and thrombosis) were compatible with molecular results, because fibrinogen Tokyo II does not have a thrombotic or hemorrhagic nature and lack of clinical signs in this family is not unexpected.

Women's Blood Donation: A Qualitative Study Exploring the Reasons for Non-Donation of Blood among Female Staff at Tehran Blood Transfusion Center

Background: The blood donation proportion of women to men is 1 to 9 in Iran. Lack of time, fear of needling and difficult access to donation sites were main reasons for not donating blood in previous studies. The aim of this study was to assess barriers of blood donation by women working in Tehran blood transfusion center.Methods: To achieve the aim of this study we designed a qualitative research. The study population came from female personnel in Tehran Blood Transfusion Center (TBTC) they were recruited by qualitative purposeful sampling with no history of blood donation. Results: Twenty-seven female personnel of TBTC aged 21-55 years old were entered to two focus group discussions. In the focus group discussion, knowledge of participants about the needs and importance of blood donation and donor acceptance criteria was desirable. There were common fears and beliefs about blood donation, similar to the results of  previous study in general female population, including weakness, concerns of having or developing anemia, fear of needling, being in reproductive age, menstruation cycle, pregnancy and childbearing stage. Some of participants believed that working in TBTC, especially in technical units, acts as a deterrent  For few females who worked in TBTC, concern of a positive test result either true or false was another cause of not blood donation. A few donors mentioned that derived plasma from female bloods was not used and also some others experienced complicated blood donation in clients. So they did not attempt to donate blood.Conclusions: At first, it seemed that female staff working in TBTC might have different perceptions about blood donation because of greater awareness than women in the general community. However the results of this study showed that reasons of not donating blood in this group of women was not different from females in the general population

Women's Blood Donation: A Qualitative Study Exploring the Reasons for Non-Donation of Blood among Female Staff at Tehran Blood Transfusion Center

Background: The blood donation proportion of women to men is 1 to 9 in Iran. Lack of time, fear of needling and difficult access to donation sites were main reasons for not donating blood in previous studies. The aim of this study was to assess barriers of blood donation by women working in Tehran blood transfusion center.Methods: To achieve the aim of this study we designed a qualitative research. The study population came from female personnel in Tehran Blood Transfusion Center (TBTC) they were recruited by qualitative purposeful sampling with no history of blood donation. Results: Twenty-seven female personnel of TBTC aged 21-55 years old were entered to two focus group discussions. In the focus group discussion, knowledge of participants about the needs and importance of blood donation and donor acceptance criteria was desirable. There were common fears and beliefs about blood donation, similar to the results of  previous study in general female population, including weakness, concerns of having or developing anemia, fear of needling, being in reproductive age, menstruation cycle, pregnancy and childbearing stage. Some of participants believed that working in TBTC, especially in technical units, acts as a deterrent  For few females who worked in TBTC, concern of a positive test result either true or false was another cause of not blood donation. A few donors mentioned that derived plasma from female bloods was not used and also some others experienced complicated blood donation in clients. So they did not attempt to donate blood.Conclusions: At first, it seemed that female staff working in TBTC might have different perceptions about blood donation because of greater awareness than women in the general community. However the results of this study showed that reasons of not donating blood in this group of women was not different from females in the general population

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

Myelodysplastic Syndrome with 6q Deletion as the Sole Chromosome Abnormality in an Iranian Patient: A Case Report with Review of Literature.

The myelodysplastic syndrome (MDS) is a highly heterogenous disorder and karyotype analysis is helpful for diagnostic and prognostic estimation. Deletion in long arm chromosome 6 (6q del) as a sole abnormality is a rare event in MDS. This is the first case report of del (6q) as the only observed diagnostic change in Iran. We also reviewed the literature of this cytogenetic lesion

Bone Structure-Related Biomarkers in Hemophilic Patients, Compared to Healthy Condition

The increased risk for developing loss of bone density in patients with hemophilia has been recently regarded. The present study was conducted to compare the levels of vitamin D and other biochemical factors affecting bone turnover in patients with hemophilia and those without this problem. The study participants were stratified into the following subgroups 1) the hemophilic patients without evidence of viral infections, 2) those with the healthy condition without evidence of infection by the viral infections. All subjects were asked to take venous blood sample to assess the levels of serum biomarkers related to bone metabolism and turnover. Comparison of different biochemical markers related to bone metabolism and turnover showed significantly lower free testosterone, total testosterone, thyroid stimulating hormone (TSH), vitamin D, calcium, osteocalcin, calcitonin, and parathormone levels as well as higher serum alkaline phosphatase, Serum C-telopeptide (CTX), and N-terminal telopeptide (NTx) levels in those hemophilic patients as compared to control group. Hemophilia can adversely affect bone structure leading to bone loss in hemophilic patients. An appropriate screening protocol pertaining to osteoporosis must be implemented in the facilities for hemophiliac patients, so that preventive and healthcare measures like more physical activity and consumption of vitamin D and calcium supplements could be provided

Comparison of Long-Acting G-CSF (PD-Lasta) with Short-Acting G-CSF (PD-Grastim) in Neutrophil Recovery Following Consolidation Chemotherapy with High-Dose Cytarabine in Acute Myeloid Leukemia: A Randomized Clinical Trial

Background: Acute myeloid leukemia (AML) patients are often neutropenic as a result of their disease alone or following their chemotherapy. In this randomized clinical trial the efficacy of Iranian short-acting (PD-Grastim) and long-acting G-CSF (PD-Lasta) were compared in term of time to recovery from neutropenia in de novo AML patients following the consolidation chemotherapy. Materials and Methods: Patients (n = 51) received one or two courses of Cytarabine and Daunorubicin as an induction. If complete remission was achieved, the treatment was followed by high-dose Cytarabine as consolidation chemotherapy. Twenty four hours after the consolidation chemotherapy, patient were randomized to receive either daily short-acting G-CSF (PD-Grastim) (300 µg/kg) or single-dose long-acting G-CSF (PD-Lasta) (6 mg). Results: The median time to recovery of neutrophils was 11.00 and 13.00 days for short-acting G-CSF (PD-Grastim) (n=22) and long-acting G-CSF (PD-Lasta) (n=29) groups, respectively (U=186.5, P>0.05 two-tailed). Incidence of adverse effects was similar in both short-acting G-CSF (PD-Grastim) and long-acting G-CSF (PD-Lasta) groups. Conclusion: Overall, data show that Iranian long-acting G-CSF (PD-Lasta) was not significantly different with Iranian short-acting G-CSF (PD-Grastim)