A history of phlebotomy therapy for hemochromatosis

Hemochromatosis was recognized as an iron-storage disease for 50 years before it was proposed to treat it by removing hemoglobin. Davis and Arrowsmith are credited with the first report that demonstrated its value. Larger series have provided statistically valid evidence of improved quality of life and increased longevity. The earlier the disease is discovered, the less risk of morbidity and mortality. Screening tests (serum iron, total iron-binding capacity, serum ferritin) are recommended for all blood relatives of index cases of this hereditary disease and for all clinics where complications of hemochromatosis may be treated: liver disorder however mild, diabetes mellitus, heart disease, arthropathies, sterility, impotence, premature menopause, and abnormal pigmentation of the skin.     

Iron deficiency anemia due to stromal tumor of the ileum

Iron-deficiency anemia occurs in 3.5 to 5.3% of adult men and postmenopausal women. Occult gastrointestinal bleeding is the cause in the vast majority of cases. After endoscopic examinations have ruled out lesions in colon and upper gastrointestinal tract, 5 to 20% of those patients remain without diagnosis. Angiodysplasias and tumors are the most common causes of occult bleeding arising from the small bowel. Their diagnosis requires complex studies with quite low yield. However, it is necessary to perform them when anemia becomes severe or persistent. We report the case of a male patient with severe and persistent iron-deficiency anemia who had a stromal gastrointestinal tumor located in the ileum.     

Effect of phlebotomy on lipid metabolism in subjects with hereditary hemochromatosis

Genetic predisposition to hereditary hemochromatosis (HH) is associated with primary hypertriglyceridemia (HTG). If iron overload influences the development of HTG, the management of these patients could be different. However, the metabolic syndrome in primary HTG is frequent; and it could partially confuse the association. The objective was to determine whether periodic bloodletting could decrease triglyceride concentrations in subjects with HH and iron overload. We retrospectively studied 155 genetically defined HH patients (C282Y homozygotes and compound heterozygotes C282Y/H63D) with iron overload and under periodic therapeutic phlebotomy. Hypertriglyceridemia (triglycerides ≥150 mg/dL) was present in 49 subjects at baseline (31.6%). Phlebotomies significantly decreased triglycerides, especially in subjects with basal HTG (from 287 mg/dL at baseline to 133 mg/dL after phlebotomies, P < .001). Blood glucose and total cholesterol did not change with phlebotomies. The triglyceride-lowering effect was obtained until ferritin concentration decreased to less than 200 μg/L and transferrin saturation to less than 40%. The triglyceride-lowering effect was obtained for glucose levels both less than and greater than 100 mg/dL. In summary, HH subjects frequently have HTG that improves after therapeutic phlebotomy, independently of basal blood glucose. Our results suggest that therapeutic phlebotomy could be a useful therapeutic approach in patients with HTG and iron overload.     

Severe copper deficiency due to excessive use of an antacid combined with pyloric stenosis

Summary A case of copper deficiency due to excessive use of an antacid combined with pyloric stenosis is described. It was demonstrated in anin vitro experiment that the addition of the antacid to a coppercontaining artificial gastric fluid resulted in a decrease of the copper concentration, presumably due to precipitation of copper oxydes. Copper deficiency disappeared after discontinuing of the antacid and beginning oral copper therapy.     

Experimental hemochromatosis due to MHC class I HFE deficiency: immune status and iron metabolism

The puzzling linkage between genetic hemochromatosis and histocompatibility loci became even more so when the gene involved, HFE, was identified. Indeed, within the well defined, mainly peptide-binding, MHC class I family of molecules, HFE seems to perform an unusual yet essential function. As yet, our understanding of HFE function in iron homeostasis is only partial; an even more open question is its possible role in the immune system. To advance on both of these avenues, we report the deletion of HFE alpha1 and alpha2 putative ligand binding domains in vivo. HFE-deficient animals were analyzed for a comprehensive set of metabolic and immune parameters. Faithfully mimicking human hemochromatosis, mice homozygous for this deletion develop iron overload, characterized by a higher plasma iron content and a raised transferrin saturation as well as an elevated hepatic iron load. The primary defect could, indeed, be traced to an augmented duodenal iron absorption. In parallel, measurement of the gut mucosal iron content as well as iron regulatory proteins allows a more informed evaluation of various hypotheses regarding the precise role of HFE in iron homeostasis. Finally, an extensive phenotyping of primary and secondary lymphoid organs including the gut provides no compelling evidence for an obvious immune-linked function for HFE.     

Nontransferrin-bound iron in plasma from hemochromatosis patients: effect of phlebotomy therapy

Plasma from patients with iron overload resulting from idiopathic hemochromatosis contains nontransferrin-bound iron, measurable by the bleomycin, assay. During venesection therapy, the concentration of bleomycin iron declines in a way highly correlated with plasma ferritin concentrations. Even when patients had been venesected to give very low total plasma iron concentrations and high transferrin iron-binding capacity, bleomycin-detectable iron was still present at low concentrations. Bleomycin-detectable iron can stimulate damaging free radical reactions, and its persistence in plasma even after prolonged venesection might contribute to the tissue damage that results from iron overload.     

Patient compliance with phlebotomy therapy for iron overload associated with hemochromatosis

OBJECTIVE: The aim of this study was to evaluate patient compliance with phlebotomy therapy of hemochromatosis-associated iron overload. METHODS: We reviewed medical records of white adults with hemochromatosis and iron overload diagnosed during medical care. We defined three elements of compliance: 1) achieving iron depletion (serum ferritin 相似文献   

Iron deficiency in a patient with extreme erythrocytosis due to cyanotic congenital heart disease

Erythrocytosis is an adaptive response to improve oxygen transport in cyanotic congenital heart disease (CCHD). However, at highly increased hematocrit levels patients may experience hyperviscosity symptoms. Iron deficiency in CCHD patients is often overlooked due to elevated hemoglobin concentrations. A 29-year-old male with CCHD was readmitted to our outpatient clinic. Red blood cells (11.65*10(12)/L), hemoglobin (25.7 g/dL), and hematocrit (80%) were extremely elevated. Measurements of iron supply showed a constellation typical for iron deficiency with low ferritin (13.2 microg/L), and high sTfR (20 mg/L). We present a case of extremely high red blood cell counts with concomitant iron deficiency. For appropriate management and to avoid misinterpretation of the iron status, ferritin and sTfR should always accomplish laboratory examination of CCHD patients.     

Iron metabolism in transgenic mice with hypoplastic anaemia due to incomplete deficiency of erythropoietin

Iron overload is a serious complication of many forms of anaemia, arising in part from mechanisms associated with compensatory increases in erythropoiesis. To investigate other mechanisms by which anaemia itself may perturb iron metabolism, without the confounding effects of compensatory erythropoiesis, we studied transgenic mice with a partially disabling insertion in the erythro-poietin gene, which manifested as incomplete erythropoietin deficiency.
Mice were studied aged 7–8 weeks. Haemoglobin concentrations were 6.6 ± 0.8 g/dl in mice homozygous for the modified erythropoietin gene, 12.9 ± 2.2 g/dl in heterozygous mice and 14.1 ± 1.0 g/dl in controls. Homozygous mice showed significant hepatic iron loading (2-fold increase in liver non-haem iron, compared with heterozygous mice and normal controls, with iron staining principally in the periportal hepatocytes). Absorption studies using ⁵⁹Fe showed increased uptake from the lumen of an in vivo isolated duodenal segment in homozygous mice, although at this point in time overall transfer of radioiron to the circulation and other tissues (mucosal transfer) was not different from controls. These observations demonstrate that anaemia can lead to hepatic iron loading even in the absence of increased erythropoiesis, and are consistent with the possibility that anaemic hypoxia can enhance mucosal iron uptake by the duodenal enterocyte.     

Juvenile hemochromatosis associated with B-thalassemia treated by phlebotomy and recombinant human erythropoietin

Juvenile hemochromatosis is a rare genetic disorder that causes iron overload. Clinical complications, which include liver cirrhosis, heart failure, hypogonadotropic hypogonadism and diabetes, appear earlier and are more severe than in HFE-related hemochromatosis. This disorder, therefore, requires an aggressive therapeutic approach to achieve iron depletion. We report here the case of a young Italian female with juvenile hemochromatosis who was unable to tolerate frequent phlebotomy because of coexistent ss-thalassemia trait. The patient was successfully iron-depleted by combining phlebotomy with recombinant human erythropoietin.     

Slc35a1 deficiency causes thrombocytopenia due to impaired megakaryocytopoiesis and excessive platelet clearance in the liver

Sialic acid is a common terminal residue of glycans on proteins and acidic sphingolipids such as gangliosides and has important biological functions. The sialylation process is controlled by more than 20 different sialyltransferases, many of which exhibit overlapping functions. Thus, it is difficult to determine the overall biological function of sialylation by targeted deletion of individual sialyltransferases. To address this issue, we established a mouse line with the Slc35a1 gene flanked by loxP sites. Slc35a1 encodes the cytidine-5’-monophosphate (CMP)-sialic acid transporter that transports CMP-sialic acid from the cytoplasm into the Golgi apparatus for sialylation. Here we report our study regarding the role of sialylation on megakaryocytes and platelets using a mouse line with significantly reduced sialylation in megakaryocytes and platelets (Plt Slc35a1^{– /–}). The major phenotype of Plt Slc35a1^–/– mice was thrombocytopenia. The number of bone marrow megakaryocytes in Plt Slc35a1^–/– mice was reduced, and megakaryocyte maturation was also impaired. In addition, an increased number of desialylated platelets was cleared by Küpffer cells in the liver of Plt Slc35a1^–/– mice. This study provides new insights into the role of sialylation in platelet homeostasis and the mechanisms of thrombocytopenia in diseases associated with platelet desialylation, such as immune thrombocytopenia and a rare congenital disorder of glycosylation (CDG), SLC35A1-CDG, which is caused by SLC35A1 mutations.