Regine Grosse

Mechanisms of plasma non-transferrin bound iron generation: insights from comparing transfused diamond blackfan anaemia with sickle cell and thalassaemia patients

In transfusional iron overload, extra‐hepatic iron distribution differs, depending on the underlying condition. Relative mechanisms of plasma non‐transferrin bound iron (NTBI) generation may account for these differences. Markers of iron metabolism (plasma NTBI, labile iron, hepcidin, transferrin, monocyte SLC40A1 [ferroportin]), erythropoiesis (growth differentiation factor 15, soluble transferrin receptor) and tissue hypoxia (erythropoietin) were compared in patients with Thalassaemia Major (TM), Sickle Cell Disease and Diamond‐Blackfan Anaemia (DBA), with matched transfusion histories. The most striking differences between these conditions were relationships of NTBI to erythropoietic markers, leading us to propose three mechanisms of NTBI generation: iron overload (all), ineffective erythropoiesis (predominantly TM) and low transferrin‐iron utilization (DBA).

Brain iron quantification by MRI in mitochondrial membrane protein-associated neurodegeneration under iron-chelating therapy

Therapeutic trials for Neurodegeneration with Brain Iron Accumulation have aimed at a reduction of cerebral iron content. A 13‐year‐old girl with mitochondrial membrane protein‐associated neurodegeneration treated with an iron‐chelating agent was monitored by R2 relaxometry, R2* relaxometry, and quantitative susceptibility mapping to estimate the brain iron content. The highly increased brain iron content slowly decreased in the substantia nigra but remained stable for globus pallidus. The estimated iron content was higher by R2* compared to R2 and quantitative susceptibility mapping, a finding not previously observed in the brain of healthy volunteers. A hypothesis explaining this discrepancy is offered.

Pancreatic iron and fat assessment by MRI-R2* in patients with iron overload diseases.

To determine the pancreatic iron (R2*) and fat content (FC) in comparison to hepatic and cardiac R2* in patients with iron overload disorders like β‐thalassemia major (TM), Diamond‐Blackfan anemia (DBA) or hereditary hemochromatosis.

Non‐Transferrin‐Bound Iron during Blood Transfusion Cycles in β‐Thalassemia Major

Abstract: Serum non‐transferrin‐bound iron (NTBI) levels assessed at arbitrary time points during transfusion cycles may not be representative if NTBI is undergoing significant changes during transfusion cycles. In 15 patients with β‐thalassemia major (age: 21 ± 6 years, liver iron concentration: 2200 ± 1200 μg/g‐liver), NTBI and other hematologic parameters (transferrin saturation, transferrin receptor) were measured weekly. The largest variation of NTBI levels between individual patients was observed at midcycle. For long‐term monitoring of NTBI levels, a particular time point relative to the last blood transfusion should be selected for blood drawing.

The prevalence of sickle cell disease and its implication for newborn screening in Germany (Hamburg metropolitan area)

Sickle cell disease is among hereditary diseases with evidence that early diagnoses and treatment improves the clinical outcome. So far sickle cell disease has not been included in the German newborn screening program despite immigration from countries with populations at risk. To determine the birth prevalence we tested 17,018 newborns. High pressure liquid chromatography and subsequent molecular‐genetic testing were used for the detection and confirmation of hemoglobin variants. The frequency of sickle cell disease‐consistent genotypes was one in 2,385 newborns. Duffy‐blood group typing showed evidence that affected children were likely of Sub‐Saharan ancestry. An inclusion of sickle cell disease into the German newborn screening seems reasonable. Pediatr Blood Cancer 2015; 9999:XX–XX

Italian Society of Hematology guidelines for thalassemia and non-invasive iron measurements

A recent article by Angelucci et al .[1][1] offers recommendations for the diagnosis, monitoring, and management of thalassemia major and related disorders. The authors’ recommendations were based on a literature survey that is itself a valuable resource for clinicians and researchers. By

Erythrocytapheresis: Do Not Forget a Useful Therapy!

In patients with pathologically altered erythrocytes, red blood cell exchange is a very efficient therapeutic measure without important side effects. With increasing migration more patients with e.g. severe malaria or sickle cell anemia have to be treated. In minor or bidirectional ABO-mismatched stem cell transplantations after reduced intensity conditioning, hemolysis can be prevented by prophylactic erythrocytapheresis. Other rare indications for red blood cell exchange are advanced erythropoietic protoporphyria and babesiosis. Sickle cell anemia can be treated with hydroxyurea. Transfusions are administered when necessary, but this results in iron overload in the long term. An expensive but safe and very efficient treatment alternative is red blood cell exchange. In cases with stroke, acute chest syndrome and other severe complications, erythrocytapheresis reproducibly breaks the vicious circle of sickling and increasing oxygen deficiency. At the same time one can aim at an exact end hematocrit. In severe malaria, erythrocytapheresis both reduces parasite load to the designated extent and reconstitutes reduced oxygen transport capacity without serious adverse effects. Here we describe our experience of erythrocytapheresis in long-term prophylaxis of complications in sickle cell anemia and sickle cell thalassemia patients. The documentation of improved iron balance was carried out by liver susceptometry.

The epidemiology of sickle cell disease in Germany following recent large-scale immigration

The epidemiology of sickle cell disease (SCD) in Germany is currently changing fundamentally with ongoing immigration. Here, we address the challenges resulting from the increased frequency, that is, the morbidity, and mortality of SCD in this population.

Analysis of a cohort of 101 CDAII patients: description of 24 new molecular variants and genotype-phenotype correlations.

Congenital dyserythropoietic anaemia type II (CDAII) is a rare autosomal recessive disease characterized by ineffective erythropoiesis, haemolysis, erythroblast morphological abnormalities, hypoglycosylation of some red blood cell membrane proteins, particularly band 3, and mutations in the SEC23B gene. We report the analysis of 101 patients from 91 families with a median follow‐up of 23 years (range 0–65); 68 patients are newly reported. Clinical and haematological parameters were separately analysed in early infancy and thereafter, when feasible. Molecular analysis of the SEC23B gene confirmed the high heterogeneity of the defect, leading to the identification of 54 different mutations, 24 of which are newly described. To evaluate the genotype‐phenotype correlation, patients were grouped according to their genotype (two missense mutations vs. one missense/one drastic mutation) and assigned to two different severity gradings based on laboratory data and on therapeutic needs; by this approach only a weak genotype‐phenotype correlation was observed in the analysed groups.

Pancreatic exocrine function and cardiac iron in patients with iron overload and with thalassemia

Patients with β‐thalassemia major at risk of cardiac iron overload have to be identified to undergo myocardial iron measurements by magnetic resonance imaging (MRI), especially, in areas and centers with restricted access to MRI. Measurements of heart iron, liver iron, and pancreatic exocrine function were performed in 44 patients by MRI‐R2* [the transverse relaxation rate R2* (= 1/T2*) characterizes the magnetic resonance decay from protons not being in phase with each other in contrast to R2 (= 1/T2)], biomagnetic liver susceptometry (LIC), and pancreatic serum amylase (PAM) and lipase (LIP), respectively. ROC analysis (area: 0.88) for detecting patients with cardiac R2* > 50 sec−1 (T2* < 20 msec) by LIP revealed a cut‐off level of 19 U/L. In conclusion, patients at risk of elevated cardiac iron levels could be identified by the exocrine pancreatic lipase and amylase function parameters. Pediatr Blood Cancer 2011; 57: 674–676.