Serum Vascular Endothelial Growth Factor (VEGF) levels in patients with alpha thalassemia

 Background: Alpha-thalassemia syndrome includes a group of hereditary anemia in which expression of alpha globin chains is decreased or absent. Impaired RBC in patients with thalassemia causes vessel involvement and endothelial cell vessel disturbance. Vascular Endothelial Growth Factor (VEGF) is the most important regulator for endothelial cell proliferation. So, the aim of this study is to compare the serum VEGF levels in patients with alpha thalassemia and normal control group.Materials and Methods: This case-control study was conducted on 17 patients with alpha thalassemia and 40 healthy people. Serum VEGF levels were measured by enzyme-linked immune sorbent assay (ELISA) kit. Then statistical analysis of results were performed using SPSS 16, value of P <0.05 was considered statistically significant.Results: Mean serum VEGF levels in case and control groups were 2294.19±1552.39 and 598.09±988.17pg/ml, respectively. Serum VEGF levels were higher in patients with alpha thalassemia (P <0.01). There was no significant correlation between serum VEGF levels and Hemoglobin. (P= 0.73).Conclusion: Our study revealed that patients with alpha thalassemia have elevated levels of serum VEGF than normal control group. Further studies with larger sample size are recommended to confirm these observations

Elevated factor VIII activity and venous thromboembolism in patients referred to the Iranian Blood Transfusion Organization: A case control study

ObjectiveA high plasma level of factor eight (FVIII) is a risk factor for venous thromboembolism (VTE). Since, there was no report about the association of elevated FVIII and VTE in Iranian population, the incidence of elevated FVIII and its association to VTE was evaluated.Materials and methods152 consecutive idiopathic VTE patients referred to the Iranian Blood Transfusion Organization (IBTO) and 130 healthy matched blood donors were studied. At least one confirmed idiopathic deep vein thrombosis (DVT) or pulmonary embolism (PE) was found among all cases. The blood samples were collected at least 3 months after DVT/PE diagnosis. The normal reference range was determined by using the Control samples of the donors. FVIII levels were measured using PTT based one-staged assay.ResultsThe FVIII levels in the cases and controls were 157.3±53.4 and 111.8±29.7, respectively. In cases, the lowest and the highest levels of FVIII were 66IU/dl and 364IU/dl, while they were 42IU/dl and 195IU/dl for the controls.There was no relation between gender, age and FVIII level in either group. The normal reference range for the controls was 52–171IU/dl. Considering the cut-off point as 180IU/dl, the elevated values were seen in 28.9% of the case group vs. 3.1% of the control group.ConclusionElevated factor VIII is likely to be a risk factor for VTE. Moreover, a new normal reference range for the Iranian population was defined

Hydroxyurea responsiveness in β-thalassemic patients is determined by the stress response adaptation of erythroid progenitors and their differentiation propensity

β-thalassemia is caused by mutations in the β-globin locus resulting in loss of, or reduced, hemoglobin A (adult hemoglobin, HbA, α2β2) production. Hydroxyurea treatment increases fetal γ-globin (fetal hemoglobin, HbF, α2γ2) expression in postnatal life substituting for the missing adult β-globin and is, therefore, an attractive therapeutic approach. Patients treated with hydroxyurea fall into three categories: i) 'responders' who increase hemoglobin to therapeutic levels; (ii) 'moderate-responders' who increase hemoglobin levels but still need transfusions at longer intervals; and (iii) 'non-responders' who do not reach adequate hemoglobin levels and remain transfusion-dependent. The mechanisms underlying these differential responses remain largely unclear. We generated RNA expression profiles from erythroblast progenitors of 8 responder and 8 non-responder β-thalassemia patients. These profiles revealed that hydroxyurea treatment induced differential expression of many genes in cells from non-responders while it h

PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-γ Pro12Ala POLYMORPHISM AND RISK OF OSTEOPENIA IN β-THALASSEMIA MAJOR PATIENTS

Genetic factors have an important role in the incidence of osteopenia in thalassemia patients. The purpose of this study was to investigate the effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ (PPARγ) gene on bone mineral density (BMD) and subsequently, the rate of osteopenia in β-thalassemia major (β-TM) patients. Blood samples were obtained from 156 β-TM patients referred to the Tehran and Qazvin Thalassemia Clinics. Samples were analyzed for polymorphisms of the PPARγ gene using polymerase chain reaction-restriction fragment length polymorphism (RFLP)-based methods. Multivariate analysis was used to investigate the relationship between the risk of osteopenia and the PPARγ gene polymorphism. Correlation analysis showed that there was a significant association between homozygous wild-type genotypes with susceptibility to osteopenia in β-TM patients (p ¼ 0.024). Logistic regression analysis showed that the risk of osteopenia was significantly (p <0.05) higher in the homozygous wild-type genotype than carriers of the rare alleles. Furthermore, the associations were strengthened in men with a homozygous wild-type genotype after adjustment for age and body mass index (BMI) (p <0.05). This study suggests that the Pro12Ala polymorphism of the PPARγ gene might be an independent factor in BMD level and osteopenia in thalassemia patients

Associates of poor physical and mental health-related quality of life in beta thalassemia-major/intermedia

&lt;ul&gt;&lt;li&gt;&lt;strong&gt;&lt;span style="font-size: 8pt;"&gt;BACKGROUND&lt;/span&gt;&lt;/strong&gt;&lt;strong&gt;&lt;span style="font-size: 8pt;"&gt;:&lt;/span&gt;&lt;/strong&gt; Using two logistic regression models, we determined the associates of poor physical and mental health related quality of life (HRQoL) among beta thalassemia patients.&lt;/li&gt;&lt;li&gt;&lt;strong&gt;&lt;span style="font-size: 8pt;"&gt;METHODS&lt;/span&gt;&lt;/strong&gt;&lt;strong&gt;&lt;span style="font-size: 8pt;"&gt;:&lt;/span&gt;&lt;/strong&gt; In this cross-sectional study which was conducted during 2006 and 2007 in outpatient adult thalassemia clinic, Blood Transfusion Organization, Tehran, Iran, Short Form 36 (SF-36) was used for measuring HRQoL in 179 patients with beta thalassemia (major/intermedia). &lt;span&gt;We determined scores higher than third quartiles of obtained PCS and MCS scores as the cutoff points of good HRQoL. Poor HRQoL was defined scores lower than first quartiles of obtained PCS and MCS scores.&lt;/span&gt; Two distinct logistic regression models were used to derive associated variables including demographic, clinical, and psychological factors.&lt;/li&gt;&lt;li&gt;&lt;strong&gt;&lt;span style="font-size: 8pt;"&gt;RESULTS&lt;/span&gt;&lt;/strong&gt;&lt;strong&gt;&lt;span style="font-size: 8pt;"&gt;:&lt;/span&gt;&lt;/strong&gt; The regression models suggested that poor physical HRQoL was positively associated with somatic comorbidities (OR = 1.472, CI = 1.021-2.197, p = 0.048) and depression score (OR = 8.568, CI = 2.325-31.573, p = 0.001). The variables that were associated with poor mental HRQoL were anxiety score (OR = 9.409, CI = 1.022-89.194, p = 0.049) and depression score (OR = 20.813, CI = 4.320-100.266, p &amp;lt; 0.001).&lt;/li&gt;&lt;li&gt;&lt;strong&gt;&lt;span style="font-size: 8pt;"&gt;CONCLUSIONS&lt;/span&gt;&lt;/strong&gt;&lt;strong&gt;&lt;span style="font-size: 8pt;"&gt;:&lt;/span&gt;&lt;/strong&gt; Depression is associated with both poor physical and mental HRQoL among patients with major/intermedia beta thalassemia, however somatic comorbidities and anxiety are associated with poor physical and mental HRQoL, respectively.&lt;/li&gt;&lt;li&gt;&lt;strong&gt;&lt;span style="font-size: 8pt;"&gt;KEYWORDS&lt;/span&gt;&lt;/strong&gt;&lt;strong&gt;&lt;span style="font-size: 8pt;"&gt;:&lt;/span&gt;&lt;/strong&gt; Thalassemia, Health Related Quality of Life, Anxiety, Depression, Somatic Comorbidities.&lt;/li&gt;&lt;/ul&gt;&lt;!--[if gte mso 9]&gt;&lt;xml&gt; &lt;w:WordDocument&gt; &lt;w:View&gt;Normal&lt;/w:View&gt; &lt;w:Zoom&gt;0&lt;/w:Zoom&gt; &lt;w:PunctuationKerning /&gt; &lt;w:ValidateAgainstSchemas /&gt; &lt;w:SaveIfXMLInvalid&gt;false&lt;/w:SaveIfXMLInvalid&gt; &lt;w:IgnoreMixedContent&gt;false&lt;/w:IgnoreMixedContent&gt; &lt;w:AlwaysShowPlaceholderText&gt;false&lt;/w:AlwaysShowPlaceholderText&gt; &lt;w:Compatibility&gt; &lt;w:BreakWrappedTables /&gt; &lt;w:SnapToGridInCell /&gt; &lt;w:WrapTextWithPunct /&gt; &lt;w:UseAsianBreakRules /&gt; &lt;w:DontGrowAutofit /&gt; &lt;/w:Compatibility&gt; &lt;w:BrowserLevel&gt;MicrosoftInternetExplorer4&lt;/w:BrowserLevel&gt; &lt;/w:WordDocument&gt; &lt;/xml&gt;&lt;![endif]--&gt;&lt;!--[if gte mso 9]&gt;&lt;xml&gt; &lt;w:LatentStyles DefLockedState="false" LatentStyleCount="156"&gt; &lt;/w:LatentStyles&gt; &lt;/xml&gt;&lt;![endif]--&gt; &lt;!--[endif]--&gt

Comparison of iron chelation effects of deferoxamine, deferasirox, and combination of deferoxamine and deferiprone on liver and cardiac T2* MRI in thalassemia maior

Background: Cardiac complications due to iron overload are the most common cause of death in patients with thalassemia major. The aim of this study was to compare iron chelation effects of deferoxamine, deferasirox, and combination of deferoxamine and deferiprone on cardiac and liver iron load measured by T2* MRI. Methods: In this study, 108 patients with thalassemia major aged over 10 years who had iron overload in cardiac T2* MRI were studied in terms of iron chelators efficacy on the reduction of myocardial siderosis. The first group received deferoxamine, the second group only deferasirox, and the third group, a combination of deferoxamine and deferiprone. Myocardial iron was measured at baseline and 12 months later through T2* MRI technique. Results: The three groups were similar in terms of age, gender, ferritin level, and mean myocardial T2* at baseline. In the deferoxamine group, myocardial T2* was increased from 12.0&plusmn;4.1 ms at baseline to 13.5&plusmn;8.4 ms at 12 months (p=0.10). Significant improvement was observed in myocardial T2* of the deferasirox group (p<0.001). In the combined treatment group, myocardial T2* was significantly increased (p<0.001).&nbsp; These differences among the three groups were not significant at the 12 months. A significant improvement was observed in liver T2* at 12 months compared to baseline in the deferasirox and the combination group. Conclusion: In comparison to deferoxamine monotherapy, combination therapy and deferasirox monotherapy have a significant impact on reducing iron overload and improvement of myocardial and liver T2* MRI

HLA-E polymorphism study in Iranian thalassemic patients

Background: Human leukocyte antigen E is a member of non-classical HLA class I. Interaction between HLA-E molecule on the target cells and inhibitory CD94/NKG2A receptor on the cell surface of natural killer (NK) cells has an important role in the regulation of immune system against pathogens; therefore different cell surface expression of HLA-E molecule plays an important role in host resistance against viral infections as well as host response to treatment. Considering this fact, we analyzed the frequency of different HLA-E genotypes (HLA-E*01010101, HLA-E*01030103, HLA-E*01010103) in major thalassemic patients who underwent frequent transfusion therapy and are thus more susceptible to infectious diseases. Methods: This study was a cross-sectional study of 104 major thalassemic patients who referred to Tehran Thalassemia Clinic between the years 2015 to 2016. Blood DNA was extracted and proliferated by sequence-specific primer polymerase chain reaction (SSP PCR). The PCR product was subjected to electrophoresis on 1.5 percent agarose gel then DNA fragment bands on the gel were detected by exposing to UV light. Furthermore, PCR products were also subjected to sequencing analysis for further confirmation. Results: From 104 patients in this study, 49 (47.1%) were man and 55 (52.9%) were women. These patients were in the age range of 16 to 43 years (mean+SD; 31.03&plusmn;4.7 year). The frequency of HLA-E*01010103 genotype (64.4 percent) was significantly (P= 0.001) higher than the genotypes of HLA-E*01010101 (15.4%) and HLA-E*01030103 (20.2%) whereas there was no difference between the frequency of HLA-E*0103 allele (52.4%) and HLA-E*0101 (47.6%). Conclusion: This is the first study that examined the HLA-E polymorphisms in Iranian thalassemic patients referred to Tehran Thalassemia Clinic. This study has shown that the frequency of HLA-E*01010103 genotype was significantly higher than other genotypes of HLA-E whereas there was no difference between the frequency of HLA-E*0103 allele and HLA-E*0101 allele. Whether different frequencies of HLA-E genotype may affect thalassemic patients&rsquo; susceptibility to blood-borne infections will be of interest for future studies

Evaluation of new cases of HCV infection in thalassaemia patients for source of infection

Background: Screening tests on blood bags is important step for blood safety. In Iran, screening for HCV started from 1996. We decided to determine the new cases of hepatitis C in our thalassemic patients, after screening of blood bags was initiated and trace backing from recipients to find their donors. Materials and Methods: The study was done on patients with complete files for HCVAb test results. Only cases that had a positive HCVAb result following a negative result were considered as new cases. For trace backing, we recorded the blood transfusions&#x2032; date and the blood bags&#x2032; number from last negative test results (HCVAb) to the first positive test result. These data were sent to the transfusion center. The suspected donors were contacted and asked to be tested again in the transfusion center. Results: A total of 395 patients were studied; 229 (58&#x0025;) males and 166 (42&#x0025;) females. Mean age was 27.5 years. We had 109 HCV (27.5&#x0025;) positive cases of whom 21 were infected after 1996. We traced the last five cases contaminated during 2003 and 2004. These five patients had 13, 10, 13, 12, and 6 donors, respectively (totally 54 donors were found). We proved the healthy state in 68.5&#x0025; (37 of 54) of our donors population. Of them, 81&#x0025; were repeated donors and 17 of 54 donors (31.5&#x0025;) could not be traced (because of change in addresses). We did not have any HCV new cases after 2004. Conclusion: We could not prove HCV transmission from donors as the source of infection. Although parenteral transmission is always on top of the list in HCV infection, the possibility of hospital and/or nursing personnel transmission and/or patient-to-patient transmission such as use of common instruments like subcutaneous Desferal&#174; infusion pumps; which the patients used for iron chelation therapy, should also be kept in mind

T2* magnetic resonance imaging of the liver in thalassemic patients in Iran

AIM: To investigate the accuracy of T2*-weighted magnetic resonance imaging (MRI T2*) in the evaluation of iron overload in beta-thalassemia major patients