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Thread: IV iron to reduce blood transfusion

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    IV iron to reduce blood transfusion


    The role of intravenous iron in anemia management and transfusion avoidance


    Auerbach M, Goodnough LT, Picard D, Maniatis A
    Transfusion 2008; published on line 12 March 2008


    Section Editor's Comments:


    Preparations of parenteral iron that had been available in the past were often associated with increased risk of significant morbidity and mortality, usually related to anaphylaxis. Newer preparations currently available have a significantly improved safety profile.
    This article reviews the available data on the use of parenteral iron, which based on limited data suggest that its use together with erythropoietin can result in the reduction of need for RBC transfusions.
    The authors of this article nonetheless emphasize the need for "larger controlled trials with IV iron to further decrease the need for RBC transfusions in settings where transfusions are likely."

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    Am J Hematol. 2008 Jan 29 [Epub ahead of print]

    Intravenous iron: From anathema to standard of care

    Auerbach M, Coyne D, Ballard H.
    Division of Hematology and Oncology, Private Practice Baltimore Maryland, Clinical Professor of Medicine, Georgetown University School of Medicine, Washington, DC.

    A growing body of literature supports the use of intravenous iron as a compliment to erythropoiesis stimulatory therapy and in a significant number of disease states where iron is necessary and oral iron is ineffective or not tolerated. The differences in efficacy, safety, and clinical nature of serious adverse events that occur with the various iron preparations are poorly understood. Misinterpretation of adverse events leads to underutilization of this important treatment modality. Understanding the history of the development and use of intravenous iron is crucial to appreciate its importance in the management of anemias of dialysis, cancer, and cancer chemotherapy and properly assess side effects and toxicity. The benefits seen with intravenous iron therapy are independent of the pretreatment levels of serum ferritin, iron, total iron binding capacity, and percent transferrin saturation. Intravenous iron has been shown to overcome hepcidin induced iron restricted erythropoiesis in iron-replete patients. Available clinical and experimental data suggest that increased utilization of intravenous iron should be considered. Am. J. Hematol., 2008. (c) 2008 Wiley-Liss, Inc.
    PMID: 18273906 [PubMed - as supplied by publisher]

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    Oncologist. 2007 Feb;12(2):231-42

    Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy

    Henry DH, Dahl NV, Auerbach M, Tchekmedyian S, Laufman LR.
    Joan Karnell Cancer Center, Pennsylvania Hospital, 230 West Washington Square, Philadelphia, PA 19106, USA. dhhenry@juno.com.

    Purpose. To evaluate the safety and efficacy of intravenous (IV) sodium ferric gluconate complex (FG), oral ferrous sulfate, or no iron to increase hemoglobin (Hb) in anemic cancer patients receiving chemotherapy and epoetin alfa. Patients and Methods. In this open-label, multicenter trial, 187 patients with chemotherapy-related anemia (Hb <11 g/dl; serum ferritin >/=100 ng/ml or transferrin saturation >/=15%) scheduled to receive chemotherapy and epoetin alfa (40,000 U subcutaneously weekly) were randomized to 8 weeks of 125 mg of IV FG weekly, 325 mg of oral ferrous sulfate three times daily, or no iron. The primary outcome was a change in Hb from baseline to endpoint, first whole-blood or red blood cell transfusion, or study withdrawal. Results. One hundred twenty-nine patients were evaluable for efficacy (FG, n = 41; oral iron, n = 44; no iron, n = 44). Mean increase in Hb was 2.4 g/dl (95% confidence interval [CI], 2.1-2.7) for FG (p = .0092 vs. oral iron; p = .0044 vs. no iron), 1.6 g/dl (95% CI, 1.1-2.1) for oral iron (p =.7695 vs. no iron), and 1.5 g/dl (95% CI, 1.1-1.9) for no iron. Hb response (increase >/=2 g/dl) was 73% for FG (p = .0099 vs. oral iron; p = .0029 vs. no iron), 46% for oral iron (p = .6687 vs. no iron), and 41% for no iron. FG was well tolerated. Conclusion. For cancer patients with chemotherapy-related anemia receiving epoetin alfa, FG produces a significantly greater increase in Hb and Hb response compared with oral iron or no iron, supporting more aggressive treatment with IV iron supplementation for these patients.
    PMID: 17296819 [PubMed - in process]

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    Kidney Int Suppl. 2006 May;(101):S13-8

    Resolving the paradigm crisis in intravenous iron and erythropoietin management

    Besarab A.
    Henry Ford Hospital, 2799 West Grand Blvd, CFP511, Detroit, Michigan 48202, USA. abesarab@ghsrenal.com

    Despite the proven benefits of intravenous (i.v.) iron therapy in anemia management, it remains underutilized in the hemodialysis population. Although overall i.v. iron usage continues to increase slowly, monthly usage statistics compiled by the US Renal Data System suggest that clinicians are not implementing continued dosing regimens following repletion of iron stores. Continued therapy with i.v. iron represents a key opportunity to improve patient outcomes and increase the efficiency of anemia treatment. Regular administration of low doses of i.v. iron prevents the recurrence of iron deficiency, enhances response to recombinant human erythropoietin therapy, minimizes fluctuation of hemoglobin levels, hematocrit levels, and iron stores, and may reduce overall costs of care. This article reviews the importance of i.v. iron dosing on a regular basis in the hemodialysis patient with iron-deficiency anemia and explores reasons why some clinicians may still be reluctant to employ these protocols in the hemodialysis setting.

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    Leukemia. 2007 Apr;21(4):627-32. Epub 2007 Jan 25.

    Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: a randomized multicenter study

    Hedenus M, Birgegård G, Näsman P, Ahlberg L, Karlsson T, Lauri B, Lundin J, Lärfars G, Osterborg A.
    Department of Internal Medicine, Sundsvall Hospital, Sundsvall, Sweden. michael.hedenus@lvn.se

    This randomized study assessed if intravenous iron improves hemoglobin (Hb) response and permits decreased epoetin dose in anemic (Hb 9-11 g/dl), transfusion-independent patients with stainable iron in the bone marrow and lymphoproliferative malignancies not receiving chemotherapy. Patients (n=67) were randomized to subcutaneous epoetin beta 30 000 IU once weekly for 16 weeks with or without concomitant intravenous iron supplementation. There was a significantly (P<0.05) greater increase in mean Hb from week 8 onwards in the iron group and the percentage of patients with Hb increase >or=2 g/dl was significantly higher in the iron group (93%) than in the no-iron group (53%) (per-protocol population; P=0.001). Higher serum ferritin and transferrin saturation in the iron group indicated that iron availability accounted for the Hb response difference. The mean weekly patient epoetin dose was significantly lower after 13 weeks of therapy (P=0.029) and after 15 weeks approximately 10 000 IU (>25%) lower in the iron group, as was the total epoetin dose (P=0.051). In conclusion, the Hb increase and response rate were significantly greater with the addition of intravenous iron to epoetin treatment in iron-replete patients and a lower dose of epoetin was required.

    PMID: 17252006 [PubMed - in process]

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    Assessing the value of intravenous ferric carboxymaltose for the treatment of postpartum anemia

    Source: Obstetrics & Gynecology 2007; 110: 267-78

    MedWire News: Large-dose injections of ferric carboxymaltose may correct postpartum anemia more reliably than iron pills, a randomized, open-label trial suggests.

    US researchers assigned 174 anemic women (hemoglobin=10 g/dl or less) to receive intravenous (iv) ferric carboxymaltose and a further 178 to receive 325 mg of oral ferrous sulfate three times a day for 6 weeks in the noninferiority study.
    The mean total dose of the investigational iron agent was 1403.1 mg, delivered in up to three weekly injections.
    The primary efficacy endpoint of the proportion of patients with at least a 2 g/dl increase in hemoglobin was similar with iv treatment and oral pills, at 96.4 versus 94.1 percent, respectively.
    However, this rise was achieved more quickly with iv treatment than pills, in 7 versus 14 days. A hemoglobin rise of at least 3.0 g/dl, or a level greater than 12.0 g/ml, was also more likely with iv treatment than with pills.
    One iv patient and five oral iron patients discontinued therapy due to drug-related adverse effects, report David Van Wyck (University of Arizona college of Medicine, Tucson) and colleagues.
    They suggest an iv iron agent that can be administered in one of three large doses may be “a useful therapeutic asset.”
    Posted: 27 August 2007
    (c) 2007 Current Medicine Group Ltd, a part of Springer Science+Business Media

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    Transfus Med. 2006 Apr;16(2):137-42

    Role of parenteral iron in transfusion requirements after total hip replacement. A pilot study

    Munoz M, Naveira E, Seara J, Palmer JH, Cuenca J, Garcia-Erce JA.
    GIEMSA, School of Medicine, University of Malaga, Malaga, Spain. mmunoz@uma.es

    An important percentage of patients undergoing total hip replacement (THR) receive allogeneic blood transfusion (ABT) to avoid the risks of acute anaemia. However, concerns about the risks of ABT have led to the search for alternatives, such as stimulation of erythropoiesis. We prospectively investigated the effect of postoperative administration of 300 mg of intravenous iron sucrose on ABT requirements in THR patients (group 2; n = 24). A previous series of 22 THR patients served as the control group (group 1). All patients were operated on by the same surgeon, using the same implant, and a set of clinical data was gathered. No adverse reactions to iron administration were observed. The group-given iron showed a trend to a lower transfusion rate (46 vs. 73%; P = 0.067) and lower transfusion index (0.96 vs. 1.68 units/patient; P = 0.038). Moreover, amongst the non-transfused patients, admission haemoglobin levels were lower in those coming from the iron group than those from the control group (12.7 +/- 0.9 vs. 14.0 +/- 1.2 g dL(-1), respectively; P = 0.017). Postoperative parenteral iron administration could be a safe and effective way to reduce ABT requirements in the THR patients. A large, randomized controlled trial to confirm these results is warranted.

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    Intravenous iron as a transfusion alternative


    Author: MANIATIS, ALICE
    Source: Transfusion Alternatives in Transfusion Medicine, Volume 9, Supplement 2, September 2007 , pp. 13-18(6)
    Publisher: Blackwell Publishing


    SUMMARY Intravenous iron has been used extensively in nephrology for decades. However, the rare but serious reactions associated with high-molecular-weight iron dextran administration have resulted in largely unjustified fears over its use, thus limiting its application in other indications. In Europe, and more recently in the USA, the availability of several iron formulations that are safe and effective - iron sucrose, ferric gluconate and low-molecular-weight iron dextran - has extended the use of intravenous iron to a number of medical settings. Although oral iron continues to be widely used in the correction of iron-deficiency anemia, it cannot cover the needs of all patients. It is slow-acting and not always well absorbed or well tolerated because of gastrointestinal disturbances. It takes weeks for oral iron to raise the hemoglobin level and months to replenish iron stores. Intravenous iron given to anemic iron-deficient patients can raise the hemoglobin level in a few days and can replenish iron stores in a few weeks. Furthermore, it has been shown to correct the anemia of chronic disease when used in combination with exogenous erythropoietin. With some preparations, the total iron deficit can be corrected with one infusion, making the treatment more cost-effective by eliminating repeat visits. Intravenous iron has contributed to decreasing the need for transfusions and to reducing the doses of erythropoiesis-stimulating agents necessary to correct anemia in nephrology, in obstetrics and gynecology, in patients with cancer undergoing chemotherapy, and in surgery and orthopedics. The safety and ease of administration of the new iron preparations continues to expand the application of intravenous iron to new areas.

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    Anemia management: intravenous iron can enable a reduction in blood transfusions - a benefit for patients and hematology wards

    Author:
    STROSS, PAUL
    Source: Transfusion Alternatives in Transfusion Medicine, Volume 9, Supplement 2, September 2007 , pp. 19-25(7)
    Publisher: Blackwell Publishing


    Abstract:
    SUMMARY Chronic iron deficiency is a common cause of symptomatic anemia, but despite this it is often overlooked or not optimally managed. Frequently, this is because the diagnosis is not confirmed and the response to treatment may be inadequate because of poor compliance, malabsorbtion or recurrent blood loss. Oral iron is blamed for many treatment-limiting gastrointestinal symptoms, and if patients are admitted to hospital with symptoms they are frequently transfused. Intravenous iron can be used to deliver a predictable dose of iron over a short time with many safety, time and economic advantages compared with blood transfusion. Unlike blood transfusion, it is easy to replace physiological storage iron or even to anticipate future blood loss. Preparations of intravenous iron are available which enable even severely anemic patients to be fully treated in two hospital visits. The speed of response to intravenous iron is fast, with rises in hemoglobin levels exceeding 2 g/dL per week in severely iron-deficient subjects. In patients with recurrent blood loss and a satisfactory response, multiple ongoing treatments with intravenous iron are feasible.

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    Clinical experience with intravenous iron


    Author: AUERBACH, MICHAEL
    Source: Transfusion Alternatives in Transfusion Medicine, Volume 9, Supplement 2, September 2007 , pp. 26-30(5)
    Publisher: Blackwell Publishing

    SUMMARY
    Recently there has been an enormous tumult over the use of the erythropoiesis-stimulating agents (ESAs) epoetin alfa and beta and darbepoetin alfa. Recommendations ranging from stopping their use in certain tumor types to withholding therapy until hemoglobin levels reach 9 g/dL or less have been proposed. These recommendations result from inconclusive and imbalanced trials favoring the placebo groups but which nonetheless raise significant concerns about the potential of ESAs to upregulate erythropoietin receptors on tumor cells. Therefore, there has never been a greater need to ensure that appropriate administration of intravenous iron is given with ESAs. In several published and soon-to-be-published trials comparing adjuvant therapy with intravenous and oral iron, without exception intravenous iron improved hemoglobin and hematopoietic responses, shortened times to maximal response, decreased exposure to ESAs and provided huge cost savings. Furthermore, these benefits were independent of patients’ pretreatment iron parameters, such as serum ferritin, transferrin saturation and the presence or absence of bone marrow hemosiderin. Nonetheless, resistance to intravenous iron usage in oncology abounds. This resistance is due to misinformation and misinterpretation of the incidence and clinical nature of serious adverse events. Now that there are three safe intravenous iron preparations, a new paradigm incorporating intravenous iron to ESA therapy in oncology needs to be examined.

    CONCLUSIONS
    Intravenous iron optimizes responses to ESA therapy, improves quality-of-life parameters and decreases transfusion requirements in chronic anemias associated with a wide variety of disease states. The available data beg for a comparison of the safety and efficacy of the available intravenous iron preparations in combination with the newer long-acting ESAs. Based on numerous published reports, high-molecular-weight iron dextran should be avoided. Intravenous iron as an adjunct to ESA therapy is inappropriately underutilized.

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