Abolish anemia, and iron deficiency w/tips on IV iron therapy from real life iron man, Michael Auerbach, MD, FACP, Clinical Professor of Medicine Georgetown University School of Medicine. Topics include oral versus IV iron therapy, safety of IV iron, ferritin cutoffs, and how to diagnosis/ treat iron deficiency in patients with chronic inflammation, chronic kidney disease, pregnancy, heart failure, and more! Take our Self Assessment Test Here.
Images by Beth Garbitelli; Written and produced by Justin Berk, MD and Matthew Watto, MD.
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History lesson on IV iron: High molecular weight iron dextran (HMWID) was the original IV iron, removed from the market in 1991 for rare, but serious and sometimes fatal anaphylaxis. Recombinant erythropoietin stimulating agents (ESAs) came out in 1988 for use in patients on dialysis, but didn’t work well until functional iron deficiency (iron restricted erythropoiesis) was discovered. When combined with IV iron, ESAs worked well for patients on dialysis and for chemotherapy induced anemia. Thus, interest in IV iron has grown (Auerbach et al. Haematologica. 2015 May; 100(5): e214–e215)
Diagnosis of iron deficiency: Transferrin saturation (tsat) <19%, Ferritin <30 ng/mL (normal range is 40-200). Many sources use a ferritin cutoff of <15 ng/mL. Ferritin is an acute phase reactant that becomes elevated during inflammation. Soluble transferrin receptor (sTfR) is not an acute phase reactant. It is inversely proportional to tissue iron availability and thus, elevated in iron deficiency. For patients with chronic kidney disease (CKD) Tsat <19% or ferritin <100 suggest iron deficiency (Dr Auerbach). KDIGO recommends IV iron for anemic, nondialysis, CKD patients with tsat <30% and ferritin <500 (Visual summary KDIGO Anemia in CKD 2012).
Questions to ask patients with anemia, iron deficiency: Do you have restless legs at night? How much ice do you eat? Can you tolerate oral iron pills? Do you get nausea or constipation? Is your stool thick and difficult to pass?
Iron absorption and metabolism: Iron gets conjugated by acids in the stomach to vitamin C, amino acids, and sugars to protect it from the alkaline rush of the pancreas, which would turn it to ferric hydroxide (rust) and block absorption. Iron gets actively transported into cells in distal duodenum and proximal jejunum. Ferroportin exports iron from the cell into the plasma where it binds transferrin and is carried to the transferrin receptor for erythropoiesis. Excess iron gets picked up by macrophages and stored until needed. Hepcidin blocks ferroportin, which impairs iron absorption/release from gut epithelial cells and circulating macrophages (Wikipedia – Hepcidin diagram).
Iron restricted erythropoiesis: Also called functional iron deficiency, or anemia of chronic inflammation (disease). Diagnosed by normal or high serum ferritin and low transferrin saturation, generally <20%. These patients poorly absorb PO iron because of elevated hepcidin levels, but will respond to IV iron, which is directly available in the blood -Dr Auerbach.
Iron deficiency without anemia: Iron deficiency has neurologic, systemic symptoms even in absence of anemia. These patients should be treated with IV iron (Dr Auerbach’s expert opinion). Fatigue improved in patients with ferritin <15 ng/mL regardless whether or not anemia was present (Krayenbuel et al. Blood 2011)
Oral iron works, but is not well tolerated. There is not single best oral iron formulation at this time -Dr Auerbach.
Who should get IV iron? Patients w/ongoing inflammation, heavy uterine bleeding, gastric bypass, hereditary hemorrhagic telangiectasia (Osler-Weber Rendu), inflammatory bowel disease, chronic kidney disease, or collagen vascular disease. Insurance will pay for IV iron if these criteria are met -Dr Auerbach2.
Iron deficiency in pregnancy: Infants are not screened for iron deficiency despite increase in cognitive and behavior abnormalities up to age 19 years old (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1540447/,
Acute blood loss anemia and iron deficiency in patients admitted to the hospital should be given IV iron even if they are transfused blood because the iron in packed red blood cells is not available for erythropoiesis and other functions of iron until those cells are broken down -Dr Auerbach.
Congestive heart failure (CHF): IV iron improves functional capacity, quality of life and CHF symptoms in patients with iron deficiency EVEN without anemia (Ankur et al IV iron for CHF NEJM 2009, Jankowska et al Eur J Heart Fail 2016)
Formulations of IV iron and Dr Auerbach’s recommend dosing
Choose from these options based on availability, cost, ease of dosing.
Minor transfusion reaction to IV iron: A syndrome occurs in approximately 1:200 patients, consisting of arthralgias, myalgias or flushing, without associated hypotension, tachycardia, tachypnea, wheezing, stridor or periorbital edema. It last 2-3 minutes. “The treatment is to chill” -Dr Auerbach. After symptoms abate, re-challenge is appropriate (Auerbach et al. Haematologica. 2015 May; 100(5): e214–e215).
Disclosures: Dr Auerbach has consulted for all of the IV iron companies, but has no relevant financial interest in any of them. The Curbsiders report no relevant financial disclosures.
Goal: Listeners will develop an approach to iron deficiency anemia diagnosis and treatment.
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