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Introduction: Hereditary hemochromatosis is an autosomal recessive disorder of iron absorption, leading to organ dysfunction. C282Y gene homozygosity is implicated in 80%-95% of cases of hereditary hemochromatosis. The clinical penetrance of this genotype remains unclear. The purpose of the study was to better describe the clinical penetrance and disease progression of C282Y homozygotes., Methods: This is a retrospective study of all individuals in Newfoundland and Labrador, Canada, homozygous for the C282Y mutation from 1999 to 2009. Using electronic health records, laboratory values, phlebotomy status, radiologic reports, and clinic records were recorded up to November 2017. Iron overload status was classified via the HealthIron study. SPSS Version 19.0 (IBM Corporation) was used for descriptive statistics. Predictors of disease penetrance were assessed with logistic regression; a Student t test was used for continuous variables, and χ tests were used for categorical variables., Results: Between 1999 and 2009, 360 individuals tested positive for C282Y/C282Y. The mean age of diagnosis was 49.1 years. Three hundred six individuals had adequate follow-up for analysis (mean 11.6 years). End-organ damage was observed in 18.3%, with 5.8% developing liver disease. End-organ damage was more frequently observed in men 24.3% vs 10.5% (P < 0.05). Clinical penetrance in postmenopausal women approached that of men 18.3%., Discussion: This is the largest reported cohort of C282Y homozygotes, followed for an extended duration of time in North America. The findings reflect outcomes in routine clinical practice and suggest that C282Y homozygosity uncommonly causes end-organ damage and liver disease.

Objective: The study evaluates the long-term deferasirox treatment of adult and pediatric patients with chronic transfusional iron overload in clinical practice., Methods: In this non-interventional study, patients were observed for up to 3 years from initiation of deferasirox treatment both prospectively and retrospectively for up to 1 year prior to enrollment. The primary end points were the proportion of patients with ≥1 notable increase in serum creatinine (SCr), and ≥1 notable increase in alanine aminotransferase (ALT)., Results: Overall, 120 patients were enrolled and 51 completed the study, with a limited 3-year dropout rate of 12.5% due to adverse events (AEs). Increase in SCr > 33% above baseline and the age-adjusted ULN (upper limit of normal) was observed in 14 patients (95%CI, 7.1-19.2). The ALT levels >5 × ULN was observed in 1 patient. Most frequent AEs reported during treatment with deferasirox include gastrointestinal disturbances., Conclusions: The long-term treatment with deferasirox was manageable in most transfusion-dependent patients with no unexpected safety findings. Regular monitoring and an adjusted deferasirox dosing strategy per local labels allowed continued iron chelation treatment and control of transfusional iron in the majority of patients on study.

Objective: The aim of this study was to evaluate the vitamin D-PTH axis in thalassemia major (TM) in relation to hepatic siderosis liver iron content., Design and Participants: In this case-controlled observational study, vitamin D-PTH axis was studied in 158 TM and 84 age and ethnicity-matched healthy nonthalassemic controls attending University College Hospital, London. Patients were classified as 25-hydroxy vitamin D (25-OHD) insufficient and sufficient if the value was less than or greater than 50 nmol/L, respectively. 25-OHD data were evaluated in relation to markers of iron load in TM., Results: In TM, 25-OHD insufficiency was 8-fold higher than the control group (odds ratio [OR], 8.1; 95% confidence interval [CI], 4.3-15.0; P<0.001). Similarly, serum PTH (P<0.001), calcium (P<0.001), and phosphate levels (P<0.05) were also significantly lower in TM compared with the controls. In TM, serum ferritin of >2500 μg/L (OR, 5.3; 95% CI, 2.3-12.3; P<0.01), liver iron of >7 mg/g dry weight (OR, 8.8; 95% CI, 3.5-10.3; P<0.001), and serum alanine aminotransferase of >50 IU/L (OR, 9.7; 95% CI, 4.0-23.5; P<0.001) were independent risk factors for low 25-OHD levels., Conclusions: Our results suggest that TM had a 8-fold higher risk of 25-OHD insufficiency compared with the controls. This was likely to be associated with hepatic hemosiderosis.

Idiopathic pulmonary hemosiderosis is a potentially fatal disease that results from episodes of alveolar hemorrhage of unknown origin. The clinical spectrum is varied, and anemia may constitute the only manifestation of illness, preceding other signs and symptoms by several months. We present the case of a 4 year-old child presenting with fever, vomiting and prostration, associated with pallor. He had microcytic and hypochromic anemia refractory to iron therapy. Gastrointestinal bleeding was ruled out after negative extensive etiological investigation. Subsequently, pulmonary infiltrates suggestive of alveolar hemorrhage were observed in the chest radiography. The cytological exam of the bronchoalveolar lavage showed hemosiderin-laden macrophages. After the etiological study, the diagnosis of idiopathic pulmonary hemosiderosis was made by exclusion. He was initiated on corticosteroid therapy, later associated to an immunosuppressive agent, with subsequent correction of anemia and of the radiological pattern. The patient is currently asymptomatic.

Idiopathic pulmonary hemosiderosis is primarily a disorder of childhood, which is characterized by hemoptysis, iron deficiency anemia, and diffuse parenchymal infiltrates on chest x-ray secondary to recurrent attacks of alveolar hemorrhage. It can be diagnosed by showing hemosiderin laden macrophages in bronchoalveolar lavage fluid after other specific causes of diffuse alveolar hemorrhage are definitely excluded. A 5-year-old male patient was admitted to our clinic with sudden-onset pallor during iron therapy given for anemia. While he was being investigated for clinical and laboratory signs mimicking hemolytic anemia, he developed cough and dyspnea. He had infiltrates on chest x-ray and scattered patchy infiltrates in both lungs on high-resolution computed tomography. Hemosiderin laden macrophages were identified in fasting gastric juice and bronchoalveolar lavage fluid. The patient was diagnosed with idiopathic pulmonary hemosiderosis and started corticosteroid therapy.

An increase of the serum ferritin may appear as an incidental finding in asymptomatic patients in the routine laboratory examination. On the one hand, ferritin reflects the iron stores of the body and can therefore indicate an iron overload of various causes. On the other hand, it is an acute phase protein and thus increases in inflammatory and malignant diseases. We aim to describe an approach to the incidental finding hyperferritinemia with possible evaluation strategy and to explain the most important differential diagnoses.

Renal hypoplasia due to a congenitally reduced number of nephrons progresses to chronic kidney disease and may cause renal anemia, given that the kidneys are a major source of erythropoietin in adults. Hypoplastic kidney (HPK) rats have only about 20% of the normal number of nephrons and develop CKD. This study assessed the renal function and hematologic changes in HPK rats from 70 to 210 d of age. HPK rats demonstrated deterioration of renal excretory function, slightly macrocytic erythropenia at all days examined, age-related increases in splenic hemosiderosis accompanied by a tendency toward increased hemolysis, normal plasma erythropoietin levels associated with increased hepatic and decreased renal erythropoietin production, and maintenance of the response for erythropoietin production to hypoxic conditions, with increased interstitial fibrosis at 140 d of age. These results indicate that increases in splenic hemosiderosis and the membrane fragility of RBC might be associated with erythropenia and that hepatic production of erythropoietin might contribute to maintaining the blood Hgb concentration in HPK rats.

The ferrokinetic indices of blood serum of rats with acetaminophen-induced hepatitis under the conditions of alimentary deprivation of protein were assessed in the work. Research was conducted on 4 groups of animals: 1 - control; 2 - rats maintained on low-protein diet; 3 - rats with acute acetaminophen-induced hepatitis, maintained on full-value ration, 4 - rats with acute acetaminophen-induced hepatitis, maintained under the conditions of alimentary deprivation of protein. The serum iron content of and serum iron binding capacity were determined colorimetrically,% of the transferrin iron saturation - as a ratio of serum iron concentration to maximal iron binding capacity of serum transferrin. The presence of hemosiderin inclusions and the character of hemosiderosis were determined in the liver sections, stained by Perls method. Qualitative determination of C-reactive protein in blood serum was carried out by immunoenzymatic method. It is shown, that in protein-deficiency rats any significant changes of iron metabolism indices and hemosiderin accumu- lation weren't observed. At the same time in rats with acetaminophen-induced hepatitis the 5-fold increase of the serum iron content against the background non-significant increase of serum iron binding capacity and the 2-fold increase of the transferrin iron saturation is established. Simultaneously in the hepatocytes and reticuloendothelial system cells the accumulation of hemosiderin in the low dispersion form is observed, equating the second degree of hemosiderosis on the background emerging of C-reactive protein in serum. In protein-deficiency rats with toxic liver injury an abrupt increase of serum iron against the background reduction of the total serum iron binding capacity and maximal saturation of transferrin by iron ions is observed. It is established, that for animals from current group the third degree of mixed type hemosiderosis and the intensification of the inflammatory reaction in liver is characterstic. Conclusion was made, that alimentary deprivation of protein under the conditions of toxic liver injury is the critical factor for structural-functional state of liver, being accompanied by the iron metabolism disturbances, development of hemosiderosis and intensification of the inflammatory reaction in liver. Research results may be used for the biochemical rationale of the therapeutic approaches for the elimination and correction of the toxic liver injury consequences.

Background: Intensive transfusion schedule and iron-chelating therapy prolonged and improved quality of life in patients with β-thalassemia (β-T) major. However, this led to an increased risk of developing impaired glucose tolerance or diabetes. In this study we analyzed variables associated with the occurrence of impaired glucose tolerance or diabetes in patients with β-T major., Methods: 388 Sardinian patients were included. Age, gender, duration of chelation therapy, body mass index, and markers of pancreatic and extrapancreatic autoimmunity were analyzed., Results: Multiple logistic regression analysis showed that anti-thyroid peroxidase (TPO) antibodies (Ab) (OR = 3.36; p = 0.008) and male gender (OR = 1.98; p = 0.025) were significantly associated with glucose impairment, while the other variables were not. Ferritin levels were significantly higher in TPOAb positive compared to TPOAb negative patients (4870 ± 1665 μg/L versus 2922 ± 2773 μg/L; p < 0.0001)., Conclusions: In patients with β-T major a progressive damage of insulin-producing cells due to secondary hemosiderosis appears to be the most reasonable mechanism associated with glucose metabolism disorders. The findings need to be confirmed with additional well designed studies to address the question of whether TPOAb may have a role in the management of these patients.