Evaluation of relationship between biochemical parameters and osteoporosis in patients with β-thalassemia major

Background: Osteoporosis is one of the late complications of β-Thalassemia major. The pathogenesis of osteoporosis depends on different factors. Ineffectiveness of hematopoiesis is the major factor, and the other factors are defected by hormonal functions or biochemical parameters. Osteoclasts hyperactivity in thalassemia increases the serum receptor activator of nuclear factor Kappa B ligand (RANKL), which plays a crucial role in bone development. This study aimed to evaluate the biochemical and hormonal parameters in patients with β-thalassemia major and their association with osteoporosis. Materials and Methods: In this case-control study, 52 patients with β-thalassemia major and 23 with thalassemia minor as controls were enrolled. The patients’ Bone Mineral Density (BMD) was measured using the Dual Energy X-ray absorptiometry (DEXA) method, and 6 mL peripheral blood of the patients and controls was obtained to detect hormonal and biochemical parameters. Data were analyzed using ANOVA, Spearman correlation coefficient, and T-test. Results: The mean of BMD in patients was 0.59±0.01 and 0.69±0.11 in femur and vertebrae, respectively. The biochemical parameters in the (patients/ controls) including calcium and alkaline phosphatase (ALK) were 9.1/ 10.2 mg/dL and 171.1/310 IU, respectively indicating a significant decrease (P< 0.05) compared to the controls. On the contrary, the mean levels of Ferritin and Zinc were 1914.18 µg/L and 113.92 mg/mL, respectively which were significantly increased (P= 0.015 and P=0.045, respectively). There was a negative correlation between the femurs BMD of patients with the RANKL level (r= - 0.8, p = 0.034) and the vertebrae BMD of patients with a Parathormone (PTH) level (r= - 0.8, P = 0.028). Conclusion: The study results indicated that the hyperactivity of RANKL and PTH in thalassemia patients might cause osteoporosis; therefore, detecting biomarkers mentioned above could be useful to diagnose osteoporosis.

Safety, clinical and laboratory characteristics of donors with thalassemia minor in living donor kidney transplant: a case series

Background Due to the increasing demand for kidney transplants, sometimes donors with underlying medical conditions can be considered for living kidney donor transplant. Thalassemia is amongst the most common inherited disorders of hemoglobin globally, which is not restricted as an exclusion criterion. However, there is currently no study examine the safety and characteristics of kidney donors with thalassemia minor. Methods All eligible live kidney donors between 2016 and 2019 with thalassemia minor at a tertiary hospital were recruited. Baseline characteristics, clinical and laboratory outcomes were investigated. Results Fifteen donors (11 women, 55.5 ± 15.0 year-old) were included with a follow-up duration of 2 (1-4) years since operation. The most prevalent gene mutation among participants was DEL-SEA. No clinical manifestations of anemia were seen but 10 participants had mild anemia diagnosed from blood tests. Cardiovascular, liver and renal function were normal before nephrectomy. Until now, all donors are alive and maintain overall good health. Anemia condition is not affected, and the post-donation eGFR = 71.04 ± 11.54 mL/min/1.73m2 is comparable to outcomes of healthy donors reported in previous studies. Two donors are at risk of proteinuria at 1-year post-transplant with A/C ratio > 30 mg/g. Conclusions Thalassemia minor individuals who are non-transfusion-dependent, without anemia clinical manifestations and have no contraindications to kidney donation are safe to be donors in short-term. An eGFR of at least 80 mL/min/1.73m2 should be considered to avoid low post-donation eGFR, and awareness should be raised on thalassemia donors with even mild albuminuria. Nephrectomy does not worsen thalassemia.

β-Thalassemia minor & renal tubular dysfunction: is there any association?

Objective Beta(β)-thalassemia is one of the most common hereditary hematologic disorders. Patients with thalassemia minor (TM) are often asymptomatic and the rate of renal dysfunction is unknown in these patients. Due to the high prevalence of renal dysfunction in Iran, the current study aimed to determine renal tubular dysfunction in patients with beta-TM. Methods In this case-control study, 40 patients with TM and 20 healthy subjects were enrolled and urinary and blood biochemical analysis was done on their samples. Renal tubular function indices were determined and compared in both groups. Data was analyzed by SPSS software, version 20.0. Results The fraction excretion (FE) of uric acid was 8.31 ± 3.98% in the case and 6.2 ± 34.71% in the control group (p = 0.048). Also, FE of potassium was significantly higher in patients with TM (3.22 ± 3.13 vs. 1.91 ± 0.81; p = 0.036). The mean Plasma NGAL level was 133.78 ± 120.28 ng/mL in patients with thalassemia and 84.55 ± 45.50 ng/mL in the control group (p = 0.083). At least one parameter of tubular dysfunction was found in 45% of patients with thalassemia. Conclusion Based on the results of this study, the prevalence of tubular dysfunction in beta-thalassemia minor patients is high. Due to the lack of knowledge of patients about this disorder, periodic evaluation of renal function in TM patients can prevent renal failure by early diagnosis.

Red cell distribution width as a differential parameter between iron deficiency anemia and a-thalassemia: an empirical approach

Iron deficiency anemia (IDA) and thalassemia minor are the most common hypochromic microcytic anemias in the world. Different formulas have been proposed to differentiate IDA from beta thalassemia minor. However, yet no formula has been proposed to differentiate IDA from alpha thalassemia minor, and Hb electrophoresis is not helpful in this hemoglobinopathy. Red cell distribution width (RDW) as indicator of changes in red blood cell size is primarily employed to differentiate IDA from other microcytic anemias. An empirical approach involving iron therapy over 1 month has shown that an increase in Hb concentration by 1 g/dL over this period is indicative of IDA, while no changes in Hb concentration are suggestive of alpha thalassemia. RDW measured after iron therapy in order to differentiate IDA and related disorders from alpha thalassemia is a better index than an increased reticulocyte count. Due to the high prevalence of IDA and costly and time-consuming nature of specific diagnostic tests, the RDW index is considered as a very sensitive and cost-effective tool in the differential diagnosis of IDA.

Endothelial dysfunction in patients with hereditary spherocytosis and b-thalassemia

Patients with hereditary spherocytosis and b-Thalassemia are characterized by the increased risk of thrombosis. The early manifestation of thrombotic complications can occur even in childhood especially after surgery. Hypercoagulability can be associated with endothelial dysfunction. The aim of this study was to investigate the hemostatic state and endothelial function in children with hereditary spherocytosis and b-thalassemia. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The hemostatic status of 18 children (10 boys and 8 girls from 1 to 13 years) with hereditary spherocytosis and of 8 children (4 boys and 4 girls from 3 to 8 years) with b-thalassemia was assessed using clotting times (activated partial thromboplastin time – APTT, thrombin time – TT, prothrombin time PT), fibrinogen levels and markers of endothelium dysfunction: endothelin-1 and thrombomodulin levels. Patients with hereditary spherocytosis were divided into 2 groups: during the hemolytic crisis (11 patients) and without the hemolytic crisis (7 patients). Patients with b-Thalassemia were divided into 3 groups: b-thalassemia major, b-thalassemia intermedia and b-thalassemia minor. APTT, TT and PT were not changed significantly between groups. We find the decreased fibrinogen levels in patients with severe condition: in hereditary spherocytosis patients during hemolytic crisis (1.9 ± 0.3 ng/ml with normal range 2–3.9 ng/ml) and in b-thalassemia major patients (1.8 ± 0.3 ng/ml with normal range 2–3.9 ng/ml). This could be caused by consumption of fibrinogen during acute hemolysis. The Thrombomodulin levels were increased in all hereditary spherocytosis patients, but median value was higher in group with hemolytic crisis (6665 pg/ml vs 5976 pg/ml with ormal value 275–909 pg/ml) indicating endothelium dysfunction and activation of blood clotting. In b-thalassemia patients Thrombomodulin levels were more elevated in b-thalassemia major and b-thalassemia intermedia (6389 ± 537 pg/ml и 6804 ± 120 pg/ml) compared to b-thalassemia minor (2727 ± 213 pg/ml) which is still higher than normal range. Endothelin-1 levels were elevated on 55% with hereditary spherocytosis patients during crisis vs 43% without. In general Endothelin-1 levels were more elevated in b-thalassemia patients (were normal in b-thalassemia minor) vs hereditary spherocytosis patients (2.33 ± 2.89 fmol/ml vs 0.95 ± 0.35 fmol/ml). Thrombomodulin and endothelin-1 levels revealed endothelium dysfunction in children with hemolysis. More dramatic changes observed in severe condition: in hereditary spherocytosis patients during hemolytic crisis and in b-thalassemia major and b-thalassemia intermedia patients.

Not every hypochromic anemia is an iron deficiency anemia. Case study

Case study of female patient with hypochromic anemia, who has been treated with iron preparations for iron deficiency anemia for a long time, is reported. A hemoglobin electrophoresis test has been performed due to treatment failure, and β-thalassemia (thalassemia minor) has been diagnosed. The data on β-thalassemia and approaches to differential diagnosis of hypochromic anemias are summarized.

Exclusive transabdominal trans-amniotic approach for chorionic villus sampling in posterior placenta: a novel approach for prenatal diagnosis of genetic disorders

Background: The objective of the study was to evaluate role and safety of transabdominal trans-amniotic approach for Chorionic villus sampling (CVS) for prenatal diagnosis of genetic disorders.Methods: Retrospective analytical study carried out on data form couples coming for pre-natal diagnosis from January 2010 to February 2021. Patient related parameters like age, gestational age; procedure related parameters like amount of sample, number of attempts required; different genetic disorder diagnosed and complications by both the approaches of CVS were recorded and analyzed.Results: Total 2287 patients undergoing CVS with mean age of 27±3.3 years were included. Majority (1621;70.9%) had CVS procedure at gestational age of 12-14 weeks. On analyzing physician’s perception, 663 (29%) patients having complete posterior placenta could not be accessible with routine trans-abdominal CVS and opted for trans-amniotic approach. Amount of sample yield and number of attempts were not statistically significant (p>0.05) by both methods of CVS. Thalassemia major was found in 948 (41.45%) followed by thalassemia minor in 525 (22.96%) patients. No statistically significant difference was found for developing complications by both the methods (p>0.05). Most common complication was pain and discomfort which was relieved by simple analgesics. Out of total 17 (0.74%) abortions; 13 (0.80%) from routine transabdominal and 4 (0.60%) from trans-amniotic route CVS with no statistically significant difference among them (p>0.05). No case of post procedure infection was observed.Conclusions: In complete posterior placenta CVS procedures usually postponed by most physicians leading to delay in diagnosis of genetic disorders. The novel method transabdominal trans-amniotic approach for CVS is effective and safe in skilled hands and can help in early prenatal diagnosis of genetic disorders.

Causes of Birth of More Than One Thalassemia Major Patient in Families in South-east of Iran: Lessons for Prevention Programs

Background: Beta-thalassemia major (TM) is one of the most common genetic diseases in Iran. Despite some efforts to reduce the incidence of TM, its incidence is still relatively high in some areas of the country. Methods: This cross-sectional study was performed on 635 families who had children with TM. The families that had more than one child with TM were enrolled. A demographic data questionnaire and a checklist containing queries about the reasons for the birth of the second or subsequent TM children were completed by each family. Finally, the data were analyzed using SPSS version 16. Results: Among the families that had more than one child with TM, 90, 23, and three families had two, three, and four children with the disease, respectively. Of the 261 patients studied, 125 (47.9%) and 136 (52.1%) had been born prior and after the implementation of the pre-marital screening program for beta-thalassemia in Iran, respectively. Also, in 29.4% of these families, parents were unaware of having thalassemia minor. In other cases, factors such as lack of knowledge about screening tests (14.0%), lack of financial compliance (13.2%), late referral for genetic tests (11.8%), and not undergoing screening tests despite recommendations (9.6%) were among the reasons declared by the families. In addition to these, religious and cultural reasons should also be mentioned as effective factors. Conclusions: This study showed that in only about 30% of the studied families, the parents were unaware of having thalassemia minor, and in other families, miscellaneous reasons were involved in the birth of the second or subsequent child with TM. In some cases, despite sufficient parental knowledge about the possibility of giving birth to a child with TM, no action was taken to prevent this event.