The Effect of Xmn -1 Polymorphism and Coinheritance of Alpha Mutations on Age at First Blood Transfusion in Iranian Patients with Homozygote IVSI-5 Mutation.

Background : Thalassemia syndromes are the most prevalent hereditary hemoglobinopathies in the world. Iran is located on the thalassemia belt.  In this study, the effect of Xmn -1 polymorphism and coinheritance of alpha mutations on age at first transfusion and also transfusion interval in Iranian thalassemic patients with homozygous IVSI-5 mutation were assessed. Materials and Methods : In this retrospective cross-sectional study 154 transfusion dependent thalassemia (TDT) patients (140 patients with ß-thalassemia major and 14 cases with ß-thalassemia intermedia) who were homozygote of IVSI-5 mutation have been participated. Blood samples were collected from participants using EDTA containers for genomic DNA analysis. DNA extraction and amplification-refractory mutation to determine the Xmn -1 polymorphism were performed. Multiplex PCR was performed to identify alpha globin deletions.  Results: The mean age of participants was 29±7, 58 of them were male and 96 were female. A significant relation between presence of Xmn -1 polymorphism and age at receiving first transfusion was detected. Coinheritance of alpha thalassemia mutation does not have significant effect on age at first transfusion or transfusion interval. Conclusion : Presence of Xmn -1 polymorphism can delay the onset of transfusion in patients with homozygote IVSI-5 mutation.

Dysgerminoma in a 15 years old phenotypically female Swyer syndrome with 46, XY pure gonadal dysgenesis: A case report.

Swyer syndrome is a 46, XY karyotype, with pure gonadal dysgenesis and primary amenorrhea. These females have primordial Mullerian structures and seek medical attention as they experience primary amenorrhea. Here, we report a 15-year-old girl, diagnosed as Swyer syndrome associated with left ovarian dysgerminoma.

Vascular Brain Damage in Thalassemia Syndrome: An Emerging Challenge.

Thalassemia syndromes are the most prevalent monogenic hemoglobinopathy in the world. In Iran, thalassemia is a public health problem because this country has been located on the thalassemia belt. In recent decades, considering that the life expectancy of patients with thalassemia has dramatically improved, some unrecognized complications have emerged in these individuals. One of these complications is a hypercoagulable state that may lead to thromboembolic events (TEE). The TEE may involve any organ in the body, including the central nervous system. Ischemic cerebrovascular events in thalassemic patients have been divided into two categories, namely overt stroke and silent cerebral infarcts (SCI). Overt stroke often develops in patients with beta-thalassemia major; however, patients with thalassemia intermedia usually suffer from SCI. This review article discusses brain vascular involvement.

Utilization of SNAP II and SNAPPE II Scores for Predicting the Mortality Rate Among a Cohort of Iranian Newborns.

BACKGROUND: The present study was conducted to determine the utility of Score for Neonatal Acute Physiology II (SNAP II) and Score for Neonatal Acute Physiology with Perinatal Extension II (SNAPPE II) scoring systems as predictors of neonatal mortality rate, and to compare the predictive value of these two methods. METHODS: In this prospective study data were gathered from infants admitted to the neonatal intensive care unit (NICU) of Imam Hossein Medical Center, Tehran, Iran, from March 2015 to December 2015. In addition to demographic data, Apgar score at 5 minutes after birth, initial and final diagnosis, SNAP II, and SNAPPE II were recorded within 24 hours after admission to the NICU. RESULTS: One hundred ninety-one newborn infants entered into the study. Birth weight (2555 ± 722 g in survival group versus 1588 ± 860 g in expired group, P<0.001), and Apgar score more than 7 at 5 minutes after birth (99.4% in survival group versus 57.1% in expired group, P<0.001) were significantly related to the mortality rate. By analyzing the data using logistic regression, it was found that SNAP II (area under the curve [AUC] = 0.992; 95% CI: 0.98-1) and SNAPPE II (AUC = 0.994; 95% CI: 0.984-1)had better value for predicting the patients' survival compared to Apgar score at 5 minutes after birth (AUC = 0.711; 95% CI: 0.568-0.855). There was no statistically significant difference in predictive value of SNAP II and SNAPPE II methods (P>0.99). CONCLUSION: According to our findings SNAP II and SNAPPE II are useful tools in predicting the mortality rate among Iranian neonates admitted to NICU. Although there was no significant difference between SNAP II and SNAPPE II, both methods had a much better predictive value compared to Apgar score at 5 minutes after birth.

Renal Hemosiderosis among Iranian Transfusion Dependent ß-Thalassemia Major Patients.

Background: In recent years, the success in management of thalassemic patients, has allowed for some previously unrecognized complications including renal abnormalities to emerge. This prospective study aimed to investigate kidney iron overload by means of MRI T2* and also renal function based on laboratory tests for early markers of glomerular and tubular dysfunction among adult Iranian transfusion-dependent thalassemia major patients. Subjects and Methods: Two-hundred and two patients with transfusion-dependent ß-thalassemia major were included in this study in Zafar Adult Thalassemia Center, Tehran, Iran. For all patients, kidney MRI T2* as well as evaluation of BUN, creatinine, uric acid, calcium, phosphorus, sodium (Na), potassium (K), total protein, albumin, cystatin C, serum ferritin ß2-microglobulin, NAG (N-acetyl-beta-D-Glucosaminidase), and urine protein were performed. Results: One-hundred and fourteen female and 88 male transfusion-dependent ß-thalassemia major patients with mean age of 30.1 ± 9.4 participated in the present study. We found that 77.7% of our patients had kidney hemosiderosis based on MRI T2*. Also, 67 patients (33.2%) had elevation of serum cystatin C, and 104 patients (51.5%) had reduced estimated glomerular filtration rate (e-GFR). Increased urinary excretion of NAG and hypercalciuria were found in 50% and 79.2% of participants, respectively. Conclusion: Renal hemosiderosis and asymptomatic renal dysfunction are prevalent among transfusion- dependent ß-thalassemia major patients which necessitate regular screening with early markers of glomerular and tubular dysfunction. Further studies in order to investigate the correlation between renal hemosiderosis and early markers of kidney dysfunction among these patients are recommended.

T2* Magnetic Resonance Imaging Study of Pancreatic Iron Overload and its Relation With the Diabetic State in Thalassemic Patients.

The present study was performed to evaluate pancreatic hemosiderosis by means of magnetic resonance imaging (MRI) T2* and its relation to the diabetic state in thalassemic patients. One hundred thirty transfusion-dependent thalassemic patients from Zafar adult thalassemia clinic, Tehran, Iran, were enrolled in the study. Data such as age, type of thalassemia, age at diagnosis, transfusion duration, ferritin level, and fasting blood sugar results were gathered. Pancreatic MRI T2* was performed for all patients. One hundred four thalassemic patients with no sign of diabetes mellitus and 26 thalassemic patients with diabetes mellitus entered the study. Out of a total of 130 patients, 102 had pancreatic hemosiderosis. Among them, 23 of 26 diabetic patients (88.5%) and 79 of 104 nondiabetic patients (76%) showed pancreatic hemosiderosis, indicating no statistically significant difference between the 2 groups. The mean pancreatic MRI T2* relaxation time for all patients was 13.99±12.43 ms. The mean relaxation was 13.62±8.38 and 14.08±13.28 ms for diabetic and nondiabetic patients, respectively, showing no statistical difference (P=0.202). In conclusion, we did not find a significant difference between diabetic and nondiabetic thalassemic patients regarding the MRI T2* relaxation time readings or the rate of pancreatic hemosiderosis. We recommend performing studies with a higher sample size and including patients from different age groups to further evaluate the role of T2* MRI of pancreatic iron overload and its relation with the diabetic state in thalassemic patients.

A Comparison of Hemostatic Changes in Splenectomized and Nonsplenectomized ß-Thalassemia Intermedia Patients.

The present study was conducted to compare the coagulation factors between splenectomized and nonsplenectomized thalassemia intermedia (TI) patients as well as a healthy control group. A total of 60 splenectomized and 60 nonsplenectomized TI patients and 60 healthy controls participated in this case-control study. The level of homocysteine, protein C and S, antithrombin III, factors V and VIII, fibrinogen, and D-dimer were measured in all groups. Our results indicated a significant reduction of protein C and S and fibrinogen in TI patients compared with healthy controls (P<0.001), as well as factor V activity (P=0.009). Also a significant elevation of D-dimer (P=0.006) and factor VIII activity (P=0.001) was observed. There was no significant difference considering homocysteine and antithrombin III level among patients and healthy controls. Also our results demonstrated that there was no significant difference considering the homeostatic parameters (except D-dimer activity) between splenectomized and nonsplenectomized TI patients after adjustment for age. In conclusion, reduction of protein C and S, fibrinogen, and factor V activity and elevation of D-dimer levels and factor VIII activity was observed in TI patients compared with healthy controls. It seems that splenectomy has little significant effect on concentration of hemostatic factors except for D-dimer activity.

Transcutaneous Bilirubinometry in Preterm and Term Newborn Infants before and during Phototherapy.

INTRODUCTION: To evaluate the accuracy of transcutaneous bilirubin measurement in a large population of newborn infants, before and during the phototherapy. PATIENTS AND METHODS: A single Bilicheck instrument was used for transcutaneous measurements. A photo-opaque patch was positioned over the measurement site prior to starting phototherapy. Transcutaneous bilirubinometry was conducted on an unpatched area of the forehead skin and on the nearby site covered by the photo-opaque patch. Readings were obtained from patched and unpatched areas and simultaneous total serum bilirubin concentrations were compared. RESULTS: We studied 134 term and 36 preterm newborns. Pre-phototherapy measurements showed a strong correlation (r: 0.929, P < 0.001, Limit of agreement: -1.8 to 3.1) between Bilicheck and serum bilirubin readings. Post-phototherapy correlation between Bilicheck and serum bilirubin readings was (r: 0.921, P < 0.001, LOA: -1.8 to 2.8) among term and (r: 0.887, P = 0.001, LOA: -1.4 to 2.7) among preterm neonates in patched areas. These correlations were (r: 0.666, P < 0.001, LOA: -1.7 to 7.3) among term and (r: 0.756, P < 0.001, LOA: -0.5 to 5.3) preterm neonates post-phototherapy in unpatched areas. CONCLUSION: BiliCheck can be safely used for the evaluation of bilirubin levels in preterm and term newborn infants under phototherapy. BiliCheck is slightly less reliable among preterm newborns.

Correlation between Heart, Liver and Pancreas Hemosiderosis Measured by MRI T2* among Thalassemia Major Patients from Iran.

INTRODUCTION: Major thalassemia patients need lifelong transfusions. The consequence of these repeated transfusions is iron accumulation in different organs. The main aim of the present study was to investigate the correlation between heart, liver and pancreas hemosiderosis in thalassemic patients from Iran. METHODS: This cross-sectional study was conducted on 164 major thalassemia patients at Zafar Adult Thalassemia Center, a referral thalassemia center in Tehran, Iran, from May to November 2014.  All patients were on regular blood transfusion at 2-4 week intervals to keep their hemoglobin at a level of 7-9 gr/dL before each transfusion. Demographic data were gathered from patients' history. MRI T2* of liver, heart and pancreas were performed for all patients. RESULTS: There were a moderate correlation between pancreatic T2* and cardiac T2* relaxation times (r = 0.42, P < 0.001), a moderate correlation between T2* of pancreas and liver (r = 0.41, P < 0.001), and a weak correlation between T2* relaxation times of heart and liver (r = 0.31, P < 0.001). CONCLUSION: Poor correlation between liver and heart, as well as a weak to moderate correlation between pancreas and liver T2* relaxation times indicate that relying on liver MRI T2* to predict the exact condition of pancreas or heart iron overload might not be a reliable approach in thalassemia major patients. Our findings suggest the advantage of using pancreas and heart MRI T2* as a non-invasive method for estimation of iron overload instead of relying on liver MRI T2*.

Intranasal midazolam compared with intravenous diazepam in patients suffering from acute seizure: a randomized clinical trial.

OBJECTIVE: Acute seizure attack is a stressful experience both for health care personnel and parents. These attacks might cause morbidity and mortality among patients, so reliable methods to control the seizure preferably at home should be developed. This study was performed to measure the time needed to control seizure attacks using intranasal midazolam compared to the common treatment (intravenous diazepam) and to evaluate its probable side effects. METHODS: This study was conducted as a not blind randomized clinical trial among 60 patients coming to Imam Ali Hospital, Zahedan, Iran. The patients were 2 months to 15 years old children coming to our emergency department suffering from an acute seizure episode. Intranasal midazolam was administered 0.2 mg/kg equally dropped in both nostrils for case group and intravenous diazepam was administered 0.3mg/kg via IV line for control group. After both treatments the time needed to control the seizure was registered by the practitioner. Pulse rate and O2 saturation were recorded at patients' entrance and in minutes 5 and 10 after drug administration. FINDINGS: The time needed to control seizure using intranasal midazolam (3.16±1.24) was statistically shorter than intravenous diazepam (6.42±2.59) if the time needed to establish IV line in patients treated by intravenous diazepam is taken into account (P<0.001). The readings for O2 saturation or heart rate did not indicate a statistically significant difference between two groups of patients either at entrance or 5 and 10 minutes after drug administration. CONCLUSION: Considering the shorter time needed to control acute seizure episodes compared to intravenous diazepam and its safety record, intranasal midazolam seems to be a good candidate to replace diazepam, as the drug of choice, in controlling this condition.

A case of concurrent proteus syndrome and hemophilia a.

BACKGROUND: Proteus syndrome is a very rare condition with less than 100 confirmed cases reported worldwide. We report a case of Proteus syndrome in a two-year-old male who has hemophilia A comorbidity. CASE PRESENTATION: A two-year-old male patient was admitted with the chief complaint of severe bleeding in mouth cavity after trauma for two weeks. At admission he was found to have petechiae on buccal mucosa and fecal discoloration due to GI bleeding. We noted multiple abnormalities in his musculoskeletal system and skin. He had lymph edema in left leg, hemihypertrophy, macrodactyly in both foots and macrocephaly. With the history of severe bleeding and recurrent blood product transfusion, we suspected a hemorrhagic disorder. The reduced level of Factor VIII activity confirmed the diagnosis of hemophilia A. Considering patient's various musculoskeletal abnormalities according to the diagnostic criteria and after ruling out similar disorders the diagnosis of Proteus syndrome was established. CONCLUSION: Because of the variability of clinical features, Proteus syndrome can be confused with other disorders of multiple tissue overgrowth. Our case of Proteus syndrome, who had hemophilia A comorbidity outlines the challenges in diagnosis of such rare combination of diseases.

Partial radiofrequency ablation of the spleen in thalassemia.

PURPOSE: To investigate the efficiency of partial radiofrequency ablation of the spleen in patients with thalassemia major and intermedia. MATERIALS AND METHODS: Partial radiofrequency ablation of the spleen was performed in 19 thalassemic patients (10 females, nine males) with a mean age of 12.7 years (age range, 7-30 years). This group of patients consisted of 11 patients with thalassemia major and nine with thalassemia intermedia. The procedure was performed under intravenous sedation and was complete in 29-35 min. RESULTS: The ratio of the ablated volume to the whole spleen ranged from 5.3% to 23% (mean, 9.83 ± 5.56%). A significant increase was found in the platelet count after radiofrequency ablation of the spleen (P = 0.002). No statistically significant difference was found in hemoglobin levels (P = 0.171) or transfusion intervals (P = 0.054) before and after radiofrequency ablation. Additionally, no statistically significant relationship was observed between the ablation ratio and hemoglobin levels (P = 0.233) and between the ablation ratio and transfusion interval (P = 0.822). No major complication occurred due to this interventional procedure. CONCLUSION: A single percutaneous radiofrequency ablation of the spleen reduces thrombocytopenia in thalassemic patients with splenomegaly but does not change the hemoglobin levels or transfusion intervals.

T2-star (T2*) magnetic resonance imaging for assessment of kidney iron overload in thalassemic patients.

BACKGROUND: Improved survival in thalassemic patients has lead to the manifestation of morbidities such as renal dysfunction. This involvement suggests the need for a reliable and non-invasive method to assess the degree of kidney iron overload. We conducted the present study to evaluate the relationship between serum ferritin levels, liver, heart, and kidney MRI gradient echo (T2*) relaxation times in thalassemic patients, as a step to evaluate the feasibility of using MRI T2* to assess the degree of kidney iron overload. METHODS: This was a prospective study of 120 (60 males, 60 females) regularly transfused thalassemic patients (mean age: 25.9 ± 9 years) who suffered from major and intermediate thalassemia. Patients attended an adult thalassemia clinic located in Tehran, Iran. Cardiac, hepatic and renal MRI T2* were performed. Serum ferritin levels were measured. RESULTS: Our results indicated a moderate correlation between kidney MRI T2* relaxation time and serum ferritin (r = -0.446, P < 0.001). Kidney MRI T2* relaxation time weakly correlated with liver MRI T2* relaxation time (r = 0.388, P < 0.001) and cardiac MRI T2* relaxation time (r = 0.338, P = 0.023). DISCUSSION: The moderate correlation between kidney MRI T2* relaxation time and serum ferritin, and its weak correlation with liver and heart T2* relaxation times indicate that relying on liver and heart MRI T2*, as well as serum ferritin levels to predict the exact condition of kidney iron overload might not be a reliable approach. Our findings suggest the use of kidney MRI T2* as a noninvasive method for evaluating renal iron overload in thalassemic patients. Further studies to investigate the relation between kidney MRI T2* relaxation times and renal function, as well as the cost benefit of using this method, are suggested.