HLA-DRB1*15:03 and HLA-DRB1*11: useful predictive alleles for alloantibody production in thalassemia patients.

BACKGROUND AND OBJECTIVES: Recently, thalassemia has been introduced as a chronic disease. In spite of prolonging life in thalassemia patients, the quality of their life has not significantly improved. One of the challenges that makes their quality of life poor is alloimmunisation which causes several complications to patients by restricting their options. Some individuals are more susceptible to developing an alloantibody than others. They are categorised as responders and non-responders. Determining responders before the first transfusion allows transfusion services to provide compatible blood and prevent alloimmunisation. The aim of the present study was to determine the relationship between HLA-DRB1*15:03, HLA-DRB1*11 and HLA-DRB1*09:01 alleles and alloimmunisation in Iranian thalassemia patients. MATERIALS AND METHODS: Antibody screening tests were performed by tube method, and HLA-DRB1 genotyping was determined by Sequence-Specific Primers (SSP-PCR) in 59 alloimmunised and 205 non-alloimmunised patients. HLA-DRB1 allele frequencies were compared between alloantibody-positive and -negative groups through the χ2 test. RESULTS: HLA-DRB1*15:03 allele frequency was significantly different between groups (P = 0·000, odds ratio (OR) = 4·193). There was a correlation between HLA-DRB1*11 and anti-K (P = 0·000, OR = 6·643). There was no association between HLA-DRB1*09:01 and alloimmunisation (P = 0·350). CONCLUSIONS: According to our results, detecting HLA-DRB1*15:03 and HLA-DRB1*11 alleles are useful in the pre-transfusion test and could determine responder patients and improve transfusion safety.

Expression analysis of microRNA-125 in patients with polycythemia vera and essential thrombocythemia and correlation with JAK2 allele burden and laboratory findings.

INTRODUCTION: The JAK2V617F mutation has emerged in recent years as a diagnostic as well as a treatment target in patients with polycythemia vera (PV) and essential thrombocythemia (ET). The disease phenotype is also influenced by other factors such as microRNA (miRNA) deregulation. The aim of this study was to investigate miR-125 expression level in these patients with those obtained from healthy control subjects and its correlation with JAK2 allele burden and laboratory findings. METHODS: In total, forty patients with a clinical diagnosis of PV and ET were examined at the time of diagnosis. Ten healthy subjects were checked as controls. We performed JAK2 V617F allele burdens measurement and expression analysis of miR-125b-5p, miR-125b-3p, miR-125a-5p, and miR-125a-3p in leukocytes isolated from peripheral blood by quantitative real-time polymerase chain reaction. RESULTS: MiR-125b-5p and miR-125a-5p were upregulated in both patients with PV (P = 0.00 and P = 0.003, respectively) and ET (P = 0.02 and P = 0.002, respectively). In PV group, a significant correlation was observed between miR-125a-5p and platelet counts (P = 0.01, r = 0.531). The correlation between miRNA and JAk2 allele burden was not significant. CONCLUSION: In conclusion, our data indicate that other factors such as aberrant miR-125 expression may influence on the disease phenotype in patients with PV and ET.

Seroepidemiology of human T-cell lymphotropic virus among Iranian adult thalassemic patients.

BACKGROUND: A large number of transfusion-dependent thalassemic patients is at a substantial risk for transfusion-transmitted infections. Human T-cell lymphotropic virus (HTLV) is a blood-borne pathogen and can be transmitted via cellular products. We aimed to evaluate the seroprevalence of HTLV in transfusion-dependent thalassemic patients referred to Tehran Adult Thalassemia Clinic. METHODS: From 2008 to 2010, 257 transfusion-dependent thalassemic patients who referred to Tehran Adult Thalassemia Clinic were enrolled. The seroprevalence of HTLV, hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV were assessed using enzyme-linked immunosorbant assay (ELISA). Also, the samples with positive result for anti-HTLVAb (by ELISA) were reassessed using Western blot for HTLV. RESULTS: Among the 257 transfusion-dependent thalassemic patients who were tested for anti-HTLVAb, 29 (11.3%, 95% CI = 7.8-15.6%) were found to be anti-HTLVAb positive by ELISA and Western blot. No case was detected to be HBsAg positive, whereas 16% had HBV seroconversion criteria, and more than 95% had anti-HBsAb in their sera. Also, 103 (40.1%) patients were HCV seropositive, 13 (5.1%) patients of which were co-infected with HCV/HTLV. Among the HTLV-infected patients, 44.8% were co-infected with HCV, whereas 39.5% of HTLV-seronegative individuals were HCV mono-infected (P > 0.05). CONCLUSION: This study showed that transfusion-dependent thalassemic patients were in higher risk for transmission of different blood-borne pathogens such as HTLV. The screening of HTLV in Iranian blood donors is recommended.

Quality of life in patients with thalassemia major.

BACKGROUND: With modern medical management, thalassemia major is now extending into adulthood and it is expected to have a negative impact on the quality of life (QOL) of the patients. The aim of this study was to evaluate quality of life in patients with thalassemia major. MATERIALS AND METHODS: This is an analytic case control study. Two hundred and fifty patients and 51 participants as controls were assessed using WHOQOL- BREF (Farsi version) questionnaire. All questions were answered based on the self-evaluated status in the past 2 weeks before enrollment and were rated on a five-point Likert scale. Therefore, the raw item score ranged from 1 to 5 and scaled in a positive direction and 6 dimensions including overall QOL, overall health, physical, psychological, social, and environmental relationship were assessed. RESULTS: Results showed that the QOL in all 6 dimensions was lower in patients compared to the controls (P< 0.05).Also age, higher education level, lower ferritin level and using oral iron chelator were associated with better QOL scores. On the other hand, cardiac disease, hepatitis C and history of psychiatric disorders were associated with impaired QOL scores. CONCLUSION: These findings were important for future refinement of national thalassemia program. So, we recommended regular screening for psychiatric disorders and facilitated access to oral iron chelators. Regular monitoring and treatment of complications especially cardiac disease and hepatitis along with strict quality control of blood products were also mandatory. Also, higher education of the patients may improve quality of life.

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.

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.

PURPOSE OF THE 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. METHODS: 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). RESULTS: 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%) CONCLUSION: A detailed comparison with similar studies on deferasirox (Exjade®) shows a promising efficacy and safety for its Iranian generic product (Osveral ®).

Endocrinopathies in patients with transfusion-dependent beta-thalassemia.

Thalassemia is common in Iran. Appropriate therapy for this disease includes a regular blood transfusion and chelation therapy. However, in this approach patients will inevitably experience side effects, particularly iron overloads in critical organs, including heart, ductless glands, and liver. This study attempted to determine prevalence of adenoidal abnormality between Iranian thalassemia patients for prediagnosis and to offer necessary medical measures. This is a descriptive nonrandomized study and included all the patients suffering from thalassemia major referring to medical centers linked with the Iranian blood transfusion organization from January 2004 to January 2005. All patients were sampled for CBC, FBS, 2-h BS, HbAlC, liver function, renal function, and endocrine disease. Initially, reports of adenoidal experiments as well as other associated parameters were provided from medical records. A total of 437 patients enrolled in the study: 5.4% suffered from diabetes, 1% had hypothyroid, and 1 person showed hypoparathyroidism. The mean levels of ferritin in diabetic and nondiabetic groups and hypothyroid and nonhypothyroid groups were not significantly different. The mean levels of ferritin among various age groups also were not significantly different. Results of a comparison between present research and similar studies conducted throughout Iran and those performed abroad on adenoidal abnormalities in thalassemia patients show that subject patients of this study statistically suffered from fewer difficulties than diabetes patients in other studies.

Bone mineral density in Iranian adolescents and young adults with beta-thalassemia major.

The authors investigated the prevalence of low bone mass in patients from Tehran, Iran, with beta-thalassemia major (n = 203), aged 10-20 years, and the potential risk factors for osteoporosis in this patient population. Prevalence of osteoporosis was 50.7% in lumbar spine, 10.8% in femur, and 7.9% in both regions with no significant difference between the two genders. The following factors were associated with low BMD: height for age and weight for age below 3rd percentile, delayed puberty or hypogonadism, age when Desferal (for iron chelation) was started, duration of Desferal therapy, and serum zinc. Low serum copper and 25(OH)D were not associated with low BMD.