[Survival analysis of the patients with Thalassemia major using parametric and semi parametric survival models]

Introduction: thalasemia Major is one of the most common anemia diseases that can be fatal if not promptly diagnosed. The survival analysis of these patients can be an appropriate strategy in determining risk factors for death in these patients. The purpose of this study was to choose the best model to determine the risk factors for death in patients with the thalasemia major using common methods in the survival analysis

Methods: the data of this retrospective cohort study, with 296 patients with thalassemia major, was collected in 2004- 2013 in Zafar Clinic in Tehran. Akaicke information Criterion was used for comparison of the models and the choice 351of the best model. Data analysis was carried out with R3.0.2 software at the significant level of 0.1

Results: the values of the Akaicke information criterion [AIC] for the parametric weibull, frailty weibull, log-normal, log-logistic, Gompertz, gamma and the semiparametric Cox were computed and found to be 27.56, 29.56, 18.73, 23.39, 26.26, 68.10, 24.73, respectively. The mean survival time for men and women were 40.2 and 39.7 years, respectively. The Log-normal model showed that age, age at the first desferal injection, onset of blood injection, the patient's birthplace, mother's education variables were significantly correlated with patient survival

Conclusion: according to the values of AIC, the parametric log-normal model was chosen and suggested as the best model

Relation between serum ferritin and liver and heart MRI T2* in beta thalassaemia major patients

There is a need for higly accurate non-invasive methods for assessing organ iron content in thalassaemia patients. This study evaluated the relation between serum ferritin level, liver enzyme levels and hepatitis C antibody and liver and heart iron deposition assessed by MRI T2 Data were obtained from the medical records of 156 thalassemia major patients in Tehran. There was a moderate negative correlation between serum ferritin and liver MRI T2 relaxation time [r= -0.535] and a weak negative correlation between serum ferritin and heart MRI T2 relaxation time [r= -0.361]. Hepatitis C infection and liver enzyme levels did not confound or modify the relation between ferritin and liver or heart MRI T2. Liver and heart MRI T2* readings were poorly correlated [r= 0. 281]. Routine evaluation of liver and heart iron content using MRI T2 is suggested to better evaluate the haemosiderosis status in thalassemia patients

Efficacy and safety of Iranian made deferasirox [Osveral]in Iranian major thalassemic patients with transfusional iron overload: a one year prospective multicentric open-label non-comparative study

To determine the efficacy, adverse effects and safety of a new Iranian generic product of deferasirox [Osveral] in Iranian transfusion dependent major thalassemic [TD-MT] patients. In 9 main thalassemia treatment centers, all of TD-MT patients [aged >/= 2 yrs] with serum ferritin [SF] levels >/= 1000 ng/ml, or >100 ml/kg of RBC transfusion, who could not tolerate parental iron chelating were recruited regardless of their previous iron chelation therapy. Periodical clinical and laboratory evaluations were conducted for adverse effects [AEs]. Primary efficacy end point was Mean of Relative Change of Serum Ferritin [MRC-SF] from the baseline level during one year. Analysis of variance [ANOVA], t test, chi-square or Fisher exact test were used for statistic analysis appropriately [P values <0.05 were considered as statistical significant]. In 407 cases the male/female ratio was 0.98. Mean age was 11.5 +/- 7.4 [2-58] years. The mean of initiating dose of Osveral and mean usage dose during the study was 23.5 +/- 4.9 mg/kg and 24.9 +/- 4.9 mg/kg respectively. MRC-SF was -11.44% +/- 38.92 and it showed significant decline in SF [P value<0.001] one hundred and forty eight patients out of 407 patients experienced at least one. AE, the most common of them were transient increase in serum creatinin [97;24.1%] and > 5 time increase in transaminases [24;5.89%].The causes of discontinuation of treatment were non-satisfactory treatment [24; 5.8%], poor or non-compliance of patients [21;5.1%], and adverse effects [13; 3.1%]. A detailed comparison with similar studies on deferasirox [Exjade] shows a promising efficacy and safety for its Iranian generic product [Osveral]

[Evaluasion and comparison of washed RBCs by closed and open systems]

Leukocyte filters are effective for WBC reduction but they cannot inhibit passing plasma proteins and as a result repeated protein entry may produce allergic transfusion reactions. To deal with this problem, washed RBC method is used. The traditional wash method is an open system through which waste products are carried away in sewers with the risk of environmental pollution. Newly introduced approach for washed RBCs consists of a closed system whereby waste products enter into a bag. In this study, the two methods were compared. The Two open and close wash methods were compared in terms of health system, leukoreduction, risk of transmission of infection and quality control. In each method, 100 bags were washed, coded and then transmitted to different units of blood culture, flowcytometry as well as quality control. The data were collected and analyzed by SPSS14. 200 bags [100 for each method] were studied. Microbiologically, there were no positive results for any of the methods. In quality control also there was not any significant difference in the two methods. In flowcytometry, we didn.t observe any significant correlation in leukocyte count in the two methods before washing [p=0.072], however.there was correlation between them after washing [p<0.0001], demonstrating that the new method was better for leukoreduction. The new washing system method was a superior way because it involves a close system where waste products are discharged into a side bag and disposed as hospital waste. Meanwhile, this approach is more convenient for leukoreduction. In our country, since we still need a washing system for some transfusions, this method is deemed to be a decent and practical one because it impedes environmental pollution

Evaluation and comparison of washed RBCs by closed and open systems

Leukocyte filters are effective for WBC reduction but they cannot inhibit passing plasma proteins and as a result repeated protein entry may produce allergic transfusion reactions. To deal with this problem, washed RBC method is used. The traditional wash method is an open system through which waste products are carried away in sewers with the risk of environmental pollution. Newly introduced approach for washed RBCs consists of a closed system whereby waste products enter into a bag. In this study, the two methods were compared. The two open and closed wash methods were compared in terms of health system, leukoreduction, risk of transmission of infection and quality control. In each method, 100 bags were washed, coded and then transmitted to different units of blood culture, flowcytometry as well as quality control. The data were collected and analyzed by SPSS 14. 200 bags [100 for each method] were studied. Microbiologically, there were no positive results for any of the methods. In quality control also there was not any significant difference in the two methods. In flowcytometry, we didn't observe any significant correlation in leukocyte count in the two methods before washing [p=0.072], however. The correlation between them after washing [p<0.0001], demonstrating that the new method was better for leukoreduction. The new washing system method was a superior way because it involves a closed system where waste products are discharged into a side bag and disposed as hospital waste. Meanwhile, this approach is more convenient for leukoreduction. In our country, since we still need a washing system for some transfusions, this method is deemed to be a decent and practical one because it impedes environmental pollution

[Trace back of thalassemic patients with positive HCV markers to their donors in adult thalassemia center]

Transfusion transmitted infection is one of the most important transfusion reactions. In this study, we tried to find new cases of HCV in thalassemic patients having referred to Adult Thalassemia Clinic after 1996 and to trace them back for sources of infection. This was a descriptive study in which all patients were studied; census method of data collection was used. Those patients with no test record before 1996 that appeared to be positive in their first test attempt were not considered a new HCV positive case. The new cases were just those whose past negative HCV Ab test results changed into positive in new test. For data analysis, SPSS version 14 was used. Out of 395 file records, 274[69.4%] were thalassemia major, and 110 [27.8%] intermediate. We had 109 HCV positive cases [27.5%] out of whom 21 were those infected after 1996. Out of the latter, 5 had complete medical records by which 54 blood donors were identified; however, only 37 [68.5%] were traced and found to be negative for HCV Ab. Noteworthy that 81% of these safe donors were shown to be repeated donors. Since there had been one or more donors whose donations had been administered to each patient with no possibility for them to be traced, we were not able to prove the transmission of HCV from donors to recipients. Other possibilities including hospital transmission, patient to patient transmission, and transmission by nurses involved in blood administration should be taken into account

[Molecular blood genotyping in patients with Thalassemia major in Tehran adult thalassemic clinic]

Blood typing by serologic methods after transfusion has limitations due to presence of donor red cells in recipients. Accurate determination of red blood cells [RBCs] antigens is very important in multitransfused patients including beta-thalassemics and sickle cell anemics. So, the aim of this study was to evaluate DNA- based methods as supplement to the hemagglutination technique to determine the red blood cell [RBC] antigen profile of multitransfused patients with beta- thalassemia. DNA was extracted from peripheral blood of 20 apparently normal people and 44 patients including 35 with beta- thalassemia [out of whom 19 had clinical evidence of delayed hemolytic transfusion reaction], 8 with thalassemia intermedia [out of whom 2 had hemolytic reaction], and one with sickle cell thalassemia. RHD/ RHC/ RHc/ RHE/ RHe/ JKA/ JKB/ FYA/ FYB/ KELL1/ KELL2 alleles were determined by PCR and were then compared with the hemagglutination method. Phenotype and genotype results were the same in all controls. The phenotypes and genotypes of 53 blood antigens of 26 patients were incompatible. Most of the discrepancies [19 cases] occurred in the Rh system, and fifteen in the Duffy and Kidd systems. The results show that screening platelet concentrates for bacterial contamination is necessary for blood transfusion centers and hospital blood banks. Blood typing by serologic method was not accurate in this study but genotyping could determine true blood groups in multitransfused patients and help in selection of RBCs without alloimmunized antigens in future transfusion attempts. Specificity, sensitivity, positive and negative predictive values of hemagglutination method for RhD antigen had good values in comparison to the molecular method. This might be due to pre- transfusion determination of RhD for thalassemic patients so as to receive Rh- matched blood units. It seems pre-transfusion blood typing of Rh and Kell antigens, which are the cause of hemolytic reactions, in comparison to the molecular method could be cost effective. In addition, typing of Rh and Kell antigens in some regular blood donors could be helpdul for selecting antigen-negative RBCs for transfusion dependent patients

[Evaluation of transfusion reactions in thalassemic patients referred to the Tehran adult thalssemia clinic]

Thalassemia is a hereditary hemolytic anemia requiring life-long transfusion treatment. The frequent blood transfusion has some side effects, including immunologic reaetions and nonimmunologics such as iron overload and transmission of some infections such as HBV, HCV and HIV. This cross-sectional study was aimed to investigate the transfusion effects in patients referred to the Adult Thalassemia Clinic, Tehran. For data collection, the patients were asked for the history of transfusion reactions, their files of medical records were surveyed with concern to transfusion status and reactions, and some laboratory data including serum ferritin and TTI were also collected. The results were analyzed using SPSS software. Foun hundreds and forty one patients comprises of 53% males and 47% females with mean age of 22.6 years were studied. They consisted of 362 [82.1%] thalassemia major and 79 [17.9%] thalassemia intermediate. The mean of ferritin level was 1856.4 ng/dl. From the studied subjects, 7 [1.6%] had history of delayed hemolytic disorder, 25 [6.1%] presented with allergy and 41 [9.9%] showed febrile transfusion reaction. The remaining 368 subjects [82.4%] showed no evidence of transfusion reactions. The records showed that 117 patients [28.4%] were HCV Ab positive, 369 [88.7%] were HBsAb positive and 80 [19.2%] were HBcAb positive, 3[0.7%] HBsAg positive. According to this results, 300 patients [70.3%] were vaccinal positive; 66 [15.5%] were immune to HBV from past infections; 40 [9.4%] were negative and 3 [0.7%] were carrier of HBV. Totally, 366 [85%] patients were immune to HBV. We had no case of HIV positive. Transfusion reaction and their documentation are very important for blood transfusion services and programming. Unfortunately, there is no statistic records of these reactions in the hospitals or there may be some unclassified data in the patients. files. Regular co-operation between hospitals and blood transfusion centers is required for collecting the information and finding total incidence of transfusion reactions. Hemovigilance or computerized network between blood bank centers in hospitals and Iran transfusion organization is the best way for collecting such data

[Evaluation of elevated FVIII in patients with thrombophilia]

Thrombus formation may form enhanced coagulation or impaired fibrinolysis. An increased tendency for the blood to clot is referred to as the hypercoagulable state or thrombophilia which includes various inherited and acquired clinical disorders or mixed conditions. There are many studies suggesting that elevated factor VIII may be a common and independent risk factor for thrombotic events. We tried to assess the level of factor VIII in patients with idiopathic thrombosis. Our cases were the patients with idiopathic venous thrombosis having referred for hypercoagulable studies to Coagulation Lab in Iranian Blood Transfusion Organization. The inclusion criterion was the occurrence of thrombotic event confirmed by objective diagnostic methods coupled with three months of follow-up without any other disorder. Our controls were from healthy blood donors and matched with the cases on sex, ethnicity, and age. Plasma of a healthy person was used to establish the normal reference range according to which our patients are compared. Factor VIII levels were measured using a one-staged assay, the PTT based Diagonistica Stago on the STA compact automated coagulation factor analyzer. SPSS and Chi-square were finally used for data analysis. One hundred fifty two cases and 130 controls enrolled. The mean factor VIII level for cases was 157.26 IU/dl [SD +/- 53.8] with the minimum level of 66 and maximum of 364 IU/dl. For controls, the mean factor VIII level was 111.78 IU/dl [SD +/- 29.68] with the minimum level of 42 and the maximum of 195 IU/dl. These levels were statistically significant and higher in the case group. The elevated FVIII level was higher in females than males [35.3% vs 23.8%] and increased with age. The normal range in the control group varied within 52-171 IU/dl, which is higher than the normal level of 50-150 IU/dl. There are many studies showing that increased FVIII level may be an independent risk factor for thrombosis. Our results suggested elevated FVIII level in 28.9% of the patients with thrombosis compared to 3.1% in the control group. So, factor VIII measurement is recommended to be practiced in routine thrombophilia screening programs

[Molecular diagnosis of B cell Non-Hodgkin Lymphoma by evaluation of immunoglobulin heavy chain gene rearrangement]

Rearrangement of V, D, and J segments of immunoglobulin heavy chain gene with inserted or deleted nucleotides within rearranged segments makes unique hypervariable regions [CDR-3]. These regions can be used for evaluation of B cell clonality for the purpose of molecular diagnosis of Non-Hodgkin Lymphoma [NHL] and for confirmatory diagnosis in suspicious cases. In this study, samples of 42 patients were collected from Taleghani, Baqhiyatalah, and Aliasghar hospitals; out of this number, there were 22 patients with diagnosis of B cell NHL, 10 with reactive hyperplasia, and 10 with malignant lymphoma. After DNA extraction from formalin fixed paraffin embedded tissues, PCR was done using consensus primers for amplification of CDR-3 region. PCR products were analyzed after heteroduplex analysis using polyacrylamide gel electrophoresis and silver stain. Results Clonal patterns in group 1 [B cell NHL], 2 [reactive and follicular hyperplasia], and 3 [morphological diagnosis without immunohistochemistry] were observed in 77.2%, 0%, and 70% of patients, respectively. Our findings are compatible with other international studies with minor differences. The diagnosis of B-cell lymphoid malignancy can frequently be substantiated by detecting clonal immunoglobulin heavy chain [IGH] gene rearrangement

[Prevalence of sexual mutation rate abnormalities in patients with beta thalassemia in Iran]

Background: thalassemia is accounted as the most common hereditary anemia through our region. Due to abnormality in synthesis of globin chains in red blood cell resulted from this disease, these globules have not natural life and then will die immediately. Appropriate therapy for this disease includes a regular monthly blood injection. However, in the approach patients will inevitably confront with side effects particularly iron overloads and iron sediment along tissue of body critical organs including heart, ductless glands and liver. Examining more research examples, by the study it attempted to determine more precisely plenty of adenoidal abnormality between the Iranian thalassemia patients for pre diagnosis and offering necessary medical measures

Materials and Methods: this was a descriptive research and included all the patients suffering from thalassemia major referring to medical centers linked with the Iranian blood transition institute. Census applied for sampling from all the patients. Initially, reports of adenoidal experiments as well as other associate parameters provided from medical folders

Results: from 437 understudy thalassemia patients, sexual mutation rate [SMR] was investigated along various age groups. There was no difference in those patients who, suffered from intermediate thalassemia and there was no relation between various age groups in the case of SMR classification [P=0/00]. Average of ferritin had no statistic difference among al 5 groups [P=0/6]

Conclusion: comparison of results between present research and similar studies conducted through Iran and those performed in abroad on growth abnormalities and puberty in thalassemia patients show that subject patients of this study statistically suffer from fewer difficulties than in case of patients in other studies

case report of thalassemia with cold agglutinin

Thalassemia is the most prevalent hereditary anemia worldwide and in our country. Lifelong blood transfusion is currently the treatment protocol of this disease, but it has some side effects; one of them is alloimmunization. Alloantibodies produce antigens against RBCs which patients do not have. The antigens are transmitted via chronic blood transfusion gradually. One of these RBC antigens is antigen I, and the antibody against it is IgM class and cold antibody. Cold agglutinins are capable of agglutinating RBCs in low temperature and may result in hemolytic anemia which is known as cold agglutinin disease [CDA]. In Iran, data regarding incidence of CAD are not available, but incidence of CAD in USA is approximately 1:300000. An 18-year-old man with beta-thalassemia major referred to the hematology lab for periodic checking of blood smear. He had clumps of RBC and RBC indices were abnormal. In repeated examination, he was known to be asymptomatic for purpose of cold agglutinins. We do not have any records or information about cold agglutinins in thalassemic patients in Iran. This case was detected only through periodic laboratory tests without any special complications on the part of the patient