Hereditary hemochromatosis: patient experiences of the disease and phlebotomy treatment

BACKGROUND: Hereditary hemochromatosis (HH) is a genetic disorder resulting in increased accumulation of dietary iron. It is associated with various clinical complications such as liver cirrhosis and diabetes. The aim of this study was to explore patients’ experiences of living with HH, the diagnosis process, and phlebotomy treatment. STUDY DESIGN AND METHODS: An online survey was developed and completed by a total of 210 HH patients across the United States (n = 70), France (n = 50), Ireland (n = 40), and the United Kingdom (n = 50). RESULTS: Of the 210 patients, 30% were induction patients, 49% were maintenance patients, and 22% had never received phlebotomy. The most common route to diagnosis was by chance (42%), although most patients (87%) reported experiencing symptoms they now associated with HH at the time of diagnosis. Fatigue (60%) and joint pain (50%) were the most frequently reported current symptoms. While 87% of patients felt that treatment with phlebotomy was “quite worthwhile” or “very worthwhile,” 52% of induction patients and 37% of maintenance patients experienced side effects “always” or “most of the time” after phlebotomy and 16% of patients would “definitely” or “probably” decide not to receive phlebotomy if alternative options were available. CONCLUSION: Diagnosis of HH is likely made late in many patients and subsequent phlebotomy treatment, while considered worthwhile by most, leads to concerns over side effects and inconvenience, often impacting patients’ lives. Greater efforts to promote awareness of the disease and reduce the treatment burden associated with phlebotomy are required to improve detection and management of this disease.     

A survey of phlebotomy among persons with hemochromatosis

BACKGROUND: One in 10 whites in the United States is a carrier for hemochromatosis and an estimated 1 in 200 is clinically affected. Early treatment with therapeutic phlebotomy to remove excess iron can prevent associated chronic diseases. However, little information is available on the amount of blood withdrawn or the rates of withdrawal from hemochromatosis patients. The patterns of therapeutic phlebotomy and the magnitude of charges in persons with hemochromatosis were surveyed. STUDY DESIGN AND METHODS: Surveys were mailed to persons with hemochromatosis identified by health care providers, blood centers, patient advocacy groups, and the Internet. There were 2362 respondents to the survey from the United States. RESULTS: Thirty-seven percent of respondents reported being voluntary blood donors prior to diagnosis. The mean rate of therapeutic phlebotomy for iron depletion was 2.6 units per month (mean duration, 13 months). The mean rate of maintenance phlebotomy was 0.5 units per month.Therapeutic phlebotomy rates varied by sex, age, reason for diagnosis, and severity of symptoms. Seventy-six percent of respondents reported full or partial insurance coverage of therapeutic phlebotomy charges. Seventy-six percent received therapeutic phlebotomy services in a hospital or physician's office and 30 percent in a blood center. Charges for therapeutic phlebotomy varied by site, with a mean cost of $90 in hospitals and $52 in blood centers. Fifty-four percent of respondents attempted to donate blood after their diagnosis but were excluded. CONCLUSION: The amount of blood withdrawn from persons with hemochromatosis is substantial. The location where patients received phlebotomy services appears to be influenced by charges and time since diagnosis.     

Soluble transferrin receptor in hemochromatosis patients during phlebotomy therapy

BACKGROUND: The monitoring of phlebotomies in hemochromatosis patients depends on iron status measured by ferritin and transferrin saturation (TS). However, in the presence of inflammation or liver injury, soluble transferrin receptor (sTfR) determination was proposed to replace ferritin for diagnosing iron deficiency (ID). The present study evaluated performances of sTfR for the prediction of iron deficiency in a large number of hemochromatosis patients under phlebotomy therapy. METHODS: We studied 52 patients undergoing therapeutic phlebotomies and obtained 2 samples from 37 patients. Biological parameters were determined before each phlebotomy began. Performances of sTfR and TS in the diagnosis of iron deficiency were compared, according to ferritin levels under 12 microg/l. RESULTS: Ferritin and TS were correlated with removed iron (r=0.473, p<0.005 and r=0.345, p<0.05, respectively) and sTfR was correlated with the decrease in hemoglobin levels induced by phlebotomies (r=-0.678, p<0.0001). Areas under Receiver Operating Characteristics (ROC) curves for sTfR and TS were not statistically different for prediction of iron deficiency and sensitivity/specificity of sTfR at 1.64 mg/l were 67/86%. CONCLUSIONS: sTfR determination could be used to predict iron depletion induced by phlebotomies when ferritin is of limited interest, to avoid the appearance of anemia.     

Therapeutic erythrocytapheresis versus phlebotomy in the initial treatment of hereditary hemochromatosis - A pilot study.

Hereditary Hemochromatosis (HH) is a genetic disorder of iron metabolism, resulting in excessive iron overload. Currently, phlebotomy is the standard effective treatment that prevents progression of tissue damage. Aim of the therapy is to reach ferritin levels between 20 and 50mugl(-1). In patients with total iron stores of more than 30g, intensive treatment by means of weekly phlebotomies during 2-3 years is required to reach this aim. More recently mechanical removal of erythrocytes through therapeutic erythrocytapheresis (TE) has become a new therapeutic modality. By means of TE, up to 1000ml erythrocytes per session can be removed, depending on patient characteristics, compared to 250ml erythrocytes per phlebotomy. Thus, TE potentially offers a more efficient method of removing iron overload with less procedures in a shorter treatment period. In a pilot study between 2002 and 2005, results from a group of HH patients treated with TE (N=6) were compared to the results of a historical control group of HH patients (N=6) treated with phlebotomy. The results showed a reduction of almost 70% in both the total number and the duration of treatments in the TE group. Although, the procedure costs compared on the basis of a single TE session were higher, the total costs for the whole treatment were comparable or cheaper with the use of TE. Future prospective studies are needed to compare both therapies in a randomized setting.     

Erythrocytapheresis versus phlebotomy in the initial treatment of HFE hemochromatosis patients: results from a randomized trial

BACKGROUND: Standard treatment of newly diagnosed HFE hemochromatosis patients is phlebotomy. Erythrocytapheresis provides a new therapeutic modality that can remove up to three times more red blood cells per single procedure and could thus have a clinical and economic benefit. STUDY DESIGN AND METHODS: To compare the number of treatment procedures between erythrocytapheresis and phlebotomy needed to reach the serum ferritin (SF) target level of 50 µg/L, a two‐treatment‐arms, randomized trial was conducted in which 38 newly diagnosed patients homozygous for C282Y were randomly assigned in a 1:1 ratio to undergo either erythrocytapheresis or phlebotomy. A 50% decrease in the number of treatment procedures for erythrocytapheresis compared to phlebotomy was chosen as the relevant difference to detect. RESULTS: Univariate analysis showed a significantly lower mean number of treatment procedures in the erythrocytapheresis group (9 vs. 27; ratio, 0.33; 95% confidence interval [CI], 0.25‐0.45; Mann‐Whitney p < 0.001). After adjustments for the two important influential factors initial SF level and body weight, the reduction ratio was still significant (0.43; 95% CI, 0.35‐0.52; p < 0.001). Cost analysis showed no significant difference in treatment costs between both procedures. The costs resulting from productivity loss were significantly lower for the erythrocytapheresis group. CONCLUSION: Erythrocytapheresis is highly effective treatment to reduce iron overload and from a societal perspective might potentially also be a cost‐saving therapy.     

Course of iron parameters in HFE‐hemochromatosis patients during initial treatment with erythrocytapheresis compared to phlebotomy

Current treatment for newly diagnosed patients with hereditary hemochromatosis (HH) and iron overload consist of weekly phlebotomy or less frequent and more personalized erythrocytapheresis. Previous observations during phlebotomy suggest an increase in intestinal iron uptake caused by lowering of hepcidin as a result of intensive bloodletting. It is not known whether such an effect is present or even more pronounced using erythrocytapheresis since a larger amount of iron is extracted per procedure. In this study we aimed to assess the effect of erythrocytapheresis on the course of iron parameters, with special focus on serum hepcidin. We performed a retrospective proof‐of‐principle observational study, comparing serum iron parameters in 12 males during the depletion phase using either phlebotomy (n = 6) or erythrocytapheresis (n = 6). Decreases in serum ferritin over time were similar for both treatments but more pronounced using erythrocytapheresis when expressed per treatment procedure. Hemoglobin did not change during erythrocytapheresis, whereas during phlebotomy decreased with 10%. Increase of erythropoietin and soluble transferrin receptor and decrease in transferrin saturation were similar for both treatments. Reduction in serum hepcidin was higher (50% versus 25% of initial value) and occurred more early using phlebotomy (10 versus 20 weeks after start). In aggregate, compared to phlebotomy, the less frequent and more personalized erythrocytapheresis leads to a more pronounced decrease in serum ferritin per treatment procedure, without a larger decrease in serum hepcidin. This may be clinically relevant and may prevent an increase in intestinal iron uptake and an ensuing vicious circle of more frequent treatment procedures. J. Clin. Apheresis 31:564–570, 2016. © 2015 Wiley Periodicals, Inc.     

Influence of abnormal breathing conditions on right ventricular function

Conclusion Clinical data collected in our intensive care unit during respiratory therapy of patients with acute respiratory faillure of various causes, confirm and illustrate some previously well-known concepts concerning the influence of breathing conditions on right ventricular performance. Venous return was found to be highly sensitive to the level of pleural pressure. On the other hand, right ventricular output impedance appears to largely depend on the degree of lung distension. Moreover, in the light of our data, a somewhat new concept might be individualized according to which the antagonistic actions of the thoracic and right ventricular pumps could severely compete in that original clinical setting represented by acute asthma.This work was supported by a Grant of the U.E.R. Paris-Ouest     

1例遗传性血色病继发心功能不全病人的护理

遗传性血色病（hereditary hemochromatosis,HH）是因铁代谢相关基因发生突变,所编码的蛋白功能发生改变,导致体内铁吸收过多、排出减少,使组织器官中铁质进行性沉积,导致脏器功能损害,产生肝硬化、糖尿病、心肌病、心律失常、性功能减退、关节炎、皮肤色素沉着等临床病症。HH 通常在40岁-50岁发病,在欧州、美州白人中常见,男性发病率高于女性,北欧患病率为0.2%-0.5%,我国发病罕见。1956年-2013年,我国公开报道血色病不足200例。血色病护理个案报道23例,以心功能衰竭为首发症状的报道则更少,相关个案报道仅3例,但均由继发性血色病引起。2012年6月19日,我院收治以心功能衰竭为首发症状的遗传性血色病病人1例,现报道如下。     

Transferrin receptor function in hereditary hemochromatosis

The binding of 125I-diferric transferrin to cultured skin fibroblasts and phytohemagglutinin-stimulated lymphocytes was studied in cells derived from individuals homozygous for hereditary hemochromatosis and from normal individuals. Receptors with a high affinity for diferric transferrin were present on all cells. Transferrin receptor number decreased by more than 50% when fibroblasts from both normal and hemochromatotic subjects were maintained in iron-supplemented medium. The number of transferrin receptors expressed by normal and hemochromatotic lymphocytes after mitogen stimulation in iron-supplemented media was less than 50% that of lymphocytes which were mitogen stimulated in standard medium. No change in the affinity of the receptors for diferric transferrin was seen in cells maintained in iron-supplemented medium. Competition experiments in the presence of deferoxamine suggested that the transferrin receptors of fibroblasts and mitogen-stimulated lymphocytes have a 70- to 100-fold higher affinity for diferric transferrin than for apotransferrin. No differences in the properties of transferrin receptors were found between patients with hereditary hemochromatosis and normal individuals. Although transferrin binding decreases when cells are exposed to high levels of iron in the medium, the failure to totally abolish transferrin binding to the receptor suggests that the concentration of diferric transferrin to which cells are exposed may be a major determinant of cellular iron loading in hereditary hemochromatosis.     

Myocardial function in patients with hereditary hemochromatosis based on echocardiographic data

In order to reveal changes in the myocardium at the preclinical stage of heart failure, 34 patients with hereditary hemochromatosis (HHC) underwent echocardiography in the M-mode. There were 26 men and 8 women aged 24 to 59 years. The control group was made up of 20 healthy persons. The HHC patients over 35 years of age (49.5 years on the average) manifested enlargement of the left ventricular cavity, an increase of the thickness of the interventricular septum and of the posterior heart wall, and reduction of pump function of the left ventricle.     

Modern diagnosis and treatment methods in hereditary hemochromatosis

The authors followed-up 76 patients with hereditary hemochromatosis whose diagnosis was confirmed by morphological signs of liver, pancreatic, pulmonary, gastric, and myocardial changes. The most informative laboratory indices of iron metabolism were defined (transferrin saturation with iron and the level of ferritin in the serum and erythrocytes). HLA typing of probands and their relatives was recommended to specify the hereditary nature of disease.     

Influence of silicone on abnormal scarring.

The problem of scarring represents a large area of an unmet medical need, since people with abnormal skin scarring may face physical and psychological consequences that may be associated with substantial emotional and financial costs. To date, treatment options are to leave the scar alone or use invasive or noninvasive management. Silicone is the key in noninvasive management, with the following overall results reported: great improvement of the scar appearance, easy to apply, painless, and almost free of side effects. When analyzing all presented results in this research sample, it becomes obvious that they are mainly based on subjective, not well-defined scar assessment by the individual without comparison to controls or rating against validated scores and therefore lacking real scientific or evidence-based criteria.     

对231例乙型肝炎伴肝功异常的学生的干预效果评价

目的研究心理干预对高校新生乙型肝炎病毒表面抗原携带者伴肝功能异常的作用,为他们的健康生活提供参考依据。方法将证实为乙型肝炎(下称乙肝)并伴肝功异常的高校新生随机分为两组,一组进行心理干预,对照组未进行心理干预。结果与对照组相比,进行心理干预的学生的肝功能和心理状况都有明显好转,差异有统计学意义(P<0.05)。结论对乙肝并伴有肝功异常的学生进行心理干预,可以明显地改善肝功能,提高在校的生活质量。