Brazilian family with hyperferritinemia-cataract syndrome: case report

ABSTRACT Hereditary hyperferritinemia-cataract syndrome is a rare autosomal dominant disease caused by a genetic mutation in the iron responsive element in the 5' untranslated region of the ferritin light chain gene. Hereditary hyperferritinemia-cataract syndrome is characterized by elevated serum ferritin levels and bilateral cataract development early in life and may be misdiagnosed as hemochromatosis. This case report describes a Brazilian family with a clinical diagnosis of hereditary hyperferritinemia-cataract syndrome, which was submitted to ferritin light chain gene sequencing. The genetic mutation c.-164C>G was identified in the 5' untranslated region. In conclusion, genetic testing can be used for accurate diagnosis of hereditary hyperferritinemia-cataract syndrome to avoid misdiagnosis of hemochromatosis, other diseases associated with iron overload or ophthalmic diseases.

Intranenous ferric carboxymaltose for the treatment of iron deficiency anemia

Nutritional iron deficiency anemia is the most common deficiency disorder, affecting more than two billion people worldwide. Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia, but in many conditions, oral iron is less than ideal mainly because of gastrointestinal adverse events and the long course needed to treat the disease and replenish body iron stores. Intravenous iron compounds consist of an iron oxyhydroxide core, which is surrounded by a carbohydrate shell made of polymers such as dextran, sucrose or gluconate. The first iron product for intravenous use was the high molecular weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to use intravenous iron for the treatment of iron deficiency anemia over many years. Intravenous ferric carboxymaltose is a stable complex with the advantage of being non- dextran-containing and a very low immunogenic potential and therefore not predisposed to anaphylactic reactions. Its properties permit the administration of large doses (15 mg/kg; maximum of 1000 mg/infusion) in a single and rapid session (15-minute infusion) without the requirement of a test dose. The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, and safety profile of ferric carboxymaltose in the treatment of patients with iron deficiency anemia.

TREATMENT OF ANEMIA AND IMPROVEMENT OF QUALITY OF LIFE AMONG PATIENTS WITH CROHN'S DISEASE: experience using ferric carboxymaltose

Objectives - Anemia is the most common hematological alteration in patients with Crohn's disease, and is frequently related to intestinal inflammatory activity. Its cause is multifactorial and mostly associated with absolute iron deficiency (iron deficiency anemia) and/or functional iron deficiency (inflammation anemia or anemia of chronic disease). It may also be identified through other causes, such as folic acid or vitamin B12 deficiency and secondary to adverse effects from medications (salicylic derivatives and immunosuppressive drugs). In the present study, patients with active Crohn's disease and anemia were evaluated and treated with intravenous ferric carboxymaltose. We discuss the therapeutic schemes (doses), safety, results and improvement of quality of life. Methods - In the present prospective study, 10 consecutive patients with Crohn's disease, with moderate to severe activity, with anemia (Hb: 6.7 to 10 g/dL), who were attended between March 2014 and March 2015, were evaluated. Six (60%) were men and four were women, all with moderate or severe anemia (hemoglobin <10 g/dL). They were treated with a maximum of three intravenous infusions of 1000 mg of ferric carboxymaltose, of at least 15 minutes in duration. It was also sought to correlate the inflammatory Crohn's disease activity degree (measured using the Crohn's Disease Activity Index, CDAI) and C-reactive protein level with the severity of anemia. The primary outcome was an increase in Hb of ≥2 g/dL and the secondary outcome was the normalization of anemia (Hb ≥12 g/dL for women and ≥13 g/dL for men) and the improvement in quality of life seen 12 weeks after the last application of carboxymaltose. Results - Among the 10 patients studied, parenteral iron supplementation was administered in three cases during hospitalization and the others received this on an outpatient basis. The total iron dose ranged from 1,000 to 2,000 mg, with an average of 1,650 mg. Crohn's disease activity measured using CDAI and C-reactive protein correlated with the intensity of anemia. An increase of 2 g/dL occurred in eight (80%) patients after 12 weeks and normalization of anemia was found in seven (70%) patients. Improvements in quality-of-life scores were found for all (100%) patients after 12 weeks. Carboxymaltose was well tolerated. Three patients presented adverse reactions (two with nausea and one with headache) of mild intensity. Conclusions - Anemia is a frequent complication for Crohn's disease patients. Intravenous iron therapy has been recommended for Crohn's disease patients, because for these patients, oral iron absorption is very limited. This is because of the inflammatory state and "blocking" of iron entry into enterocytes through hepcidin action on ferroportin, along with the elevated rates of gastrointestinal adverse events that compromise adherence to treatment and possibly aggravate the intestinal inflammatory state. The degree of Crohn's disease activity, as measured using CDAI and C-reactive protein, correlates with the severity of anemia. Carboxymaltose is a safe drug, which can be administrated in high doses (up to 1,000 mg per application per week) and corrects anemia and iron stocks over a short period of time, with consequent improvement in quality of life.

Objetivos - Anemia é a alteração hematológica mais comum em portadores de doença de Crohn, estando frequentemente relacionada à atividade inflamatória intestinal. Sua causa é multifatorial, está associada na maioria das vezes com deficiência absoluta de ferro (anemia ferropriva) e/ou deficiência funcional de ferro (anemia da inflamação ou anemia de doença crônica), podendo também ser identificada outras causas como deficiência de ácido fólico ou vitamina B12 e secundária a efeitos adversos de medicamentos (derivados salicílicos e imunossupressores). Neste trabalho, avaliamos portadores de doença de Crohn em atividade com anemia que foram tratados com carboximaltose férrica endovenosa, e discutimos os esquemas terapêuticos (doses), a segurança e os resultados, assim como a melhora da qualidade de vida. Métodos - Neste estudo prospectivo, avaliamos 10 consecutivos pacientes portadores de doença de Crohn de moderada a grave atividade com anemia (Hb: 6,7 a 10 g/dL) que foram atendidos no período de março de 2014 a março de 2015. Eram seis (60%) do sexo masculino e quatro do sexo feminino, todos com anemia moderada ou grave (hemoglobina <10g/dL), tratados com no máximo três infusões de 1000 mg de carboximaltose férrica por via endovenosa em, pelo menos, 15 minutos. Procurou-se também correlacionar o grau de atividade inflamatória da doença de Crohn (mensuração realizada com o IADC-índice de atividade da doença de Crohn) e dosagem da proteína C reativa com a gravidade da anemia. O desfecho primário foi aumento da Hb de ≥2 g/dL e desfecho secundário a normalização da anemia (Hb ≥12 g/dL para mulheres e ≥13 g/dL para homens) e melhora na qualidade de vida após 12 semanas da aplicação da última dose de carboximaltose férrica. Resultados - Dos 10 pacientes estudados, em 3 a suplementação parenteral de ferro foi realizada durante internação hospitalar, o restante em regime ambulatorial. A dose total de ferro administrada variou de 1.000 a 2.000 mg, sendo a média de 1.650 mg. A atividade da doença de Crohn mensurada pelo IADC e pelo PCR se correlacionou com a intensidade da anemia. O aumento de 2 g/dL ocorreu em oito (80%) pacientes após 12 semanas e a normalização da anemia foi observada em sete (70%). Melhora do escore de qualidade de vida foi observada em todos (100%) após 12 semanas. A carboximaltose férrica foi bem tolerada, três pacientes apresentaram reações adversas (2 - náusea e 1 - cefaléia) de leve intensidade. Conclusões - Anemia é uma complicação frequente em portadores de doença de Crohn. A terapia com ferro por via endovenosa tem sido a recomendada em portadores de doença de Crohn, pois nestes pacientes a absorção do ferro oral é bastante limitada devido ao estado inflamatório e "bloqueio" da entrada de ferro nos enterócitos por ação da hepcidina sobre a ferroportina, além das elevadas taxas de eventos adversos gastrointestinais que comprometem a adesão ao tratamento e podem agravar o estado inflamatório intestinal. O grau de atividade da doença de Crohn mensurado pelo IADC e PCR se correlaciona com a severidade da anemia. A carboximaltose férrica é uma droga segura, pode ser administrada em altas doses (até 1.000 mg por aplicação por semana), corrige a anemia e os estoques de ferro em curto espaço de tempo, com consequente melhora da qualidade de vida.

Prevenção e tratamento da deficiência de ferro: vantagens e desvantagens, mitos e verdades dos principais compostos de ferro / Prevention and treatment of iron deficiency: advantages and disadvantages, myths and truths about the main iron formulations

A deficiência de ferro representa um importante problema de saúde pública, particularmente em crianças, mulheres e gestantes. A suplementação oral de ferro é o meio barato, seguro e efetivo de prevenir e corrigir a deficiência de ferro. Muitos compostos de ferro estão disponíveis, variando amplamente de acordo com a sua dosagem, formulação, estado químico, eficácia e eventos adversos. Neste artigo revisamos os dados disponíveis na literatura quanto a comparação entre sulfato ferroso, complexo férrico polimaltosado, ferro aminoquelato e o ferro carbonila, que correspondem as principais formulações utilizadas atualmente na prática clínica para o tratamento da deficiência de ferro no Brasil...

Non-HFE hemochromatosis

Hereditary hemochromatosis (HH) is an autosomal recessive disorder classically related to HFE mutations. However, since 1996, it is known that HFE mutations explain about 80% of HH cases, with the remaining around 20% denominated non-HFE hemochromatosis. Nowadays, four main genes are implicated in the pathophysiology of clinical syndromes classified as non-HFE hemochromatosis: hemojuvelin (HJV, type 2Ajuvenile HH), hepcidin (HAMP, type 2B juvenile HH), transferrin receptor 2 (TFR2, type 3 HH) and ferroportin (SLC40A1, type 4 HH). The aim of this review is to explore molecular, clinical and management aspects of non-HFE hemochromatosis.

The influence of hydroxyurea on oxidative stress in sickle cell anemia

OBJECTIVE: The oxidative stress in 20 sickle cell anemia patients taking hydroxyurea and 13 sickle cell anemia patients who did not take hydroxyurea was compared with a control group of 96 individuals without any hemoglobinopathy. METHODS: Oxidative stress was assessed by thiobarbituric acid reactive species production, the Trolox-equivalent antioxidant capacity and plasma glutathione levels. RESULTS: Thiobarbituric acid reactive species values were higher in patients without specific medication, followed by patients taking hydroxyurea and the Control Group (p < 0.0001). The antioxidant capacity was higher in patients taking hydroxyurea and lower in the Control Group (p = 0.0002 for Trolox-equivalent antioxidant capacity and p < 0.0292 for plasma glutathione). Thiobarbituric acid reactive species levels were correlated with higher hemoglobin S levels (r = 0.55; p = 0.0040) and lower hemoglobin F concentrations(r = -0.52; p = 0.0067). On the other hand, plasma glutathione levels were negatively correlated with hemoglobin S levels (r = -0.49; p = 0.0111) and positively associated with hemoglobin F values (r = 0.56; p = 0.0031). CONCLUSION: Sickle cell anemia patients have high oxidative stress and, conversely, increased antioxidant activity. The increase in hemoglobin F levels provided by hydroxyurea and its antioxidant action may explain the reduction in lipid peroxidation and increased antioxidant defenses in these individuals.

Efficacy and safety of intravenous iron sucrose in treating adults with iron deficiency anemia

BACKGROUND: Iron deficiency is the most common disorder in the world, affecting approximately 25 percent of the world`s population and the most common cause of anemia. OBJECTIVE: To evaluate the efficacy and safety of intravenous iron sucrose (IS) in the treatment of adults with iron deficiency anemia METHODS: Eighty-six adult patients with iron deficiency anemia, who had intolerance or showed no effect with oral iron therapy, received a weekly dose of 200 mg of intravenous iron sucrose until the hemoglobin level was corrected or until receiving the total dose of intravenous iron calculated for each patient RESULTS: The mean hemoglobin and serum ferritin levels were 8.54 g/dL and 7.63 ng/mL (pre-treatment) and 12.1 g/dL and 99.0 ng/mL (post-treatment) (p-value < 0.0001), respectively. The average increases in hemoglobin levels were 3.29 g/dL for women and 4.58 g/dL for men; 94 percent of male and 84 percent of female patients responded (hemoglobin increased by at least 2 g/dL) to intravenous iron therapy. Correction of anemia was obtained in 47 of 69 (68.1 percent) female patients and in 12 of 17 male (70.6 percent) patients. A total of 515 intravenous infusions of iron sucrose were administered and iron sucrose was generally well tolerated with no moderate or serious adverse drug reactions recorded by the investigators. CONCLUSIONS: Our data confirm that the use of intravenous iron sucrose is a safe and effective option in the treatment of adult patients with iron deficiency anemia who lack satisfactory response to oral iron therapy. Intravenous iron sucrose is well tolerated and with a clinically manageable safety profile when using appropriate dosing and monitoring. The availability of intravenous iron sucrose would potentially improve compliance and thereby reduce morbidities from iron deficiency.

Intravenous iron therapy: how far have we come?

Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia (IDA) because of its effectiveness and low cost. But unfortunately in many iron deficient conditions, oral iron is a less than the ideal treatment mainly because of adverse events related to the gastrointestinal tract as well as the long course required to treat anemia and replenish body iron stores. The first iron product for intravenous use was high-molecular-weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to prescribe intravenous iron in the treatment of iron deficiency anemia for many years. In 1999 and 2001, two new intravenous iron preparations (ferric gluconate and iron sucrose) were introduced into the market as safer alternatives to iron dextran. Over the last five years, three new intravenous iron dextran-free preparations have been developed and have better safety profiles than the more traditional intravenous compounds, as none require test doses and all these products are promising in respect to a more rapid replacement of body iron stores (15-60 minutes/infusion) as they can be given at higher doses (from 500 mg to more than 1000 mg/infusion). The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, safety profile and toxicity of intravenous iron for the treatment of iron deficiency anemia.

Incidência de aloimunização eritrocitária em pacientes com doença falciforme: experiência de um centro em São Paulo / Incidence of alloimunization in sickle cell disease: experience of a center in São Paulo

Objective: To identify the incidence of alloimmunization in sickle cell disease patients, as well as autoantibodies and the phenotypic profile of these patients for the following erythrocyte antigen groups: Rh, Kell, Kidd, Duffy and MNS. Methods: fifty-seven patients were evaluated during follow-up at the Anemia Outpatient Clinic of Irmandade da Santa Casa de São Paulo, where a search for irregular antibodies and phenotyping was carried out. Results: Patients' median alloimmunization age in sickle cell disease was 25 years, and irregular antibodies were found in 22.6% of them. Anti-Kell antibody was the most frequent (7.5%) followed by anti-C (5.7%). Conclusion: The prevalence of alloimmunization and of patients with autoantibodies among individuals with sickle cell disease followed at the Anemia Outpatient Clinic of Irmandade da Santa Casa de Misericórdia de São de Paulo was determined. The risk of alloimmunization was higher in patients who received more than 3 red blood cell units in the past 2 years. The most prevalent alloantibodies were anti-Kell and anti-C.

Objetivo: Identificar a incidência de aloimunização em pacientes com doença falciforme, a incidência de autoanticorpos e o perfil fenotípico dos pacientes para os seguintes grupos de antígenos eritrocitários: Rh, Kell, Kidd, Duffy e MNS. Métodos: Foram avaliados 57 pacientes em acompanhamento no Ambulatório de Anemias da Irmandade da Santa Casa de São Paulo, sendo realizada a pesquisa de anticorpos irregulares e a fenotipagem eritrocitária. Resultados: A mediana de idade foi de 25 anos, sendo que 22,6% dos pacientes apresentavam anticorpos irregulares. O anticorpo anti-Kell foi o mais frequente (7,5%), seguido de anti-C (5,7%). Conclusão: Foi determinada a prevalência de aloimunização e de pacientes com autoanticorpos em indivíduos com anemia falciforme seguidos no Ambulatório de Anemias da Irmandade da Santa Casa de Misericórdia de São de Paulo. O risco de aloimunização foi maior em pacientes que receberam mais do que 3 unidades de hemácias nos últimos 2 anos. Os aloanticorpos mais prevalentes foram anti-Kell e anti-C.

Brazilian Guidelines for transcranial doppler in children and adolescents with sickle cell disease

BACKGROUND: Sickle cell disease is the most common monogenic hereditary disease in Brazil. Although strokes are one of the main causes of morbidity and mortality in these patients, the use of transcranial Doppler to identify children at risk is not universally used. OBJECTIVE: To develop Brazilian guidelines for the use of transcranial Doppler in sickle cell disease children and adolescents, so that related health policies can be expanded, and thus contribute to reduce morbidity and mortality. METHODS: The guidelines were formulated in a consensus meeting of experts in transcranial Doppler and sickle cell disease. The issues discussed were previously formulated and scientific articles in databases (MEDLINE, SciELO and Cochrane) were carefully analyzed. The consensus for each question was obtained by a vote of experts on the specific theme. RESULTS: Recommendations were made, including indications for the use of transcranial Doppler according to the sickle cell disease genotype and patients age; the necessary conditions to perform the exam and its periodicity depending on exam results; the criteria for the indication of blood transfusions and iron chelation therapy; the indication of hydroxyurea; and the therapeutic approach in cases of conditional transcranial Doppler. CONCLUSION: The Brazilian guidelines on the use of transcranial doppler in sickle cell disease patients may reduce the risk of strokes, and thus reduce the morbidity and mortality and improve the quality of life of sickle cell disease patients.