Iron Deficiency Anemia

How do you define IDA in CKD patients?

When would you consider IV iron for a patient with advanced CKD presenting a high ferritin level?

When do you use oral vs IV iron in CKD patients?

Why should we prescribe oral iron every other day vs every day?

Oral iron supplements may acutely increase the circulating plasma hepcidin level that represents the main regulator of plasma iron concentrations. Increased hepcidin levels downregulate ferroportin, and ultimately lead to a reduced iron efflux:

1. Reduced duodenal iron absorption
2. Reduced iron recycling by macrophages
3. Reduced iron release from hepatocytes stores

The acute increase in hepcidin levels following oral supplementation persists for 24 hours.  This leads to a decreased iron absorption from any subsequent oral supplement taken later on the same or next day. This explains why alternate dosing can result in a higher fractional iron absorption compared to daily dosing.

References

1. Stoffel NU, Zeder C, Brittenham GM, Moretti D, Zimmermann MB. Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. Haematologica. 2020;105(5):1232-1239.
2. Moretti D, Goede JS, Zeder C, et al. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood. 2015;126(17):1981-1989.

Is treatment warranted for patients presenting a normal hemoglobin level (120g/L) but low ferritin levels (11 mcg/L)?

It is important to highlight that there are number of non-hematologic complications associated with iron deficiency (ID) despite having a normal hemoglobin level. These include hair loss, pica, and restless leg syndrome among many others.

In the case that the patient is presenting ID symptoms, oral iron supplements should be used as a first treatment option as there is evidence that targeting a ferritin of 50 mcg/L significantly improves quality of life.

In the case that the patient is entirely asymptomatic, and does not wish to take oral supplements, it would still be important to review underlying causes of low iron stores and have a follow-up after 6 months to reassess the situation.

Reference

Expert opinion Dr. Karima Khamisa

What is the threshold at which I should initiate treatment for iron deficiency in chronic heart failure?

Iron deficiency thresholds in CHF patients are as follows:

• Serum ferritin 100-299 mcg/L AND TSAT <20%
• or a Serum ferritin <100 mcg/L

A patient presenting a TSAT <20% and serum ferritin <300 mcg/L should be treated with iron therapy with a target of TSAT ≥20% and a serum ferritin >100 mcg/L.

Anemia of inflammation is generally considered in the case of a patient presenting a TSAT <20% but with serum ferritin ≥300 mcg/L. Serum ferritin becomes difficult to interpret in the context of inflammation and further tests should be considered such as the % hypochromic reticulocytes and mean hemoglobin reticulocyte concentration (CHr) with a CHr value <30 pg being the most predictive value for response to IV iron therapy. Finally, if a patient presents with a TSAT>20% and a serum ferritin <100 mcg/L, iron therapy should be given until serum ferritin reaches a level of 100 mcg/L.

Reference:

1. Tim Goodnough L, Comin-Colet J, Leal-Noval S, et al. Management of anemia in patients with congestive heart failure. Am J Hematol. 2017;92(1):88-93.

Please discuss the safety of IV iron formulations

Intravenous iron therapy use is increasing due to its effectiveness and safety profile. It is important to note that the newer iron formulations are associated with a much lower incidence of adverse reactions. The main side effect observed with intravenous iron therapy is related to infusion reactions. Mild infusion reactions occur at a rate of 1:200 and do not progress to more serious reactions. They are characterized by transient symptoms including facial flushing, truncal myalgia, pressure in the chest or lumbar region, dizziness, and nausea. This type of mild infusion reaction is typically called the Fishbane reaction and does not require treatment with epinephrine or antihistamines.

Serious adverse reactions are considered to be quite rare and occur at a rate of less than 1: 200,000. These hypersensitivity reactions may occur either suddenly or as a rapid worsening of the symptoms of a mild or moderate reaction. They will require immediate management including treatment as they may be life-threatening for the patient. The typical symptoms observed in patients with such reactions are hypotension, wheezing, stridor, loss of consciousness and periorbital edema.

References:

1. Auerbach M, et al. Treatment of iron deficiency anemia in adults. UpToDate. Last Updated July 2020.
2. DeLoughery TG. Safety of Oral and Intravenous Iron. Acta Haematol. 2019;142(1):8-12.

What are the different oral and IV iron preparations?

Other oral formulations may be used if the patient is intolerant or experiences gastro-intestinal side effects. 

*Estimates: Costs may differ across Canada   Here are the different IV iron formulations available in Canada. 

CKD=Chronic kidney disease, NDD=Non-dialysis dependent, HDD=hemodialysis-dependent, PDD=Peritoneal-dialysis-dependent, ESA= Erythropoiesis-stimulating agents

References

1. American regent, Inc. ^Pr Venofer® Product Monograph. Date of Preparation: January 23, 2019
2. Pfizer Canada Inc ^Pr Monoferric^TM Product Monograph. Date of Preparation: June 22, 2018
3. Sanofi-aventis Canada Inc. Ferrlecit® Product Monograph. Date of Preparation: December 13, 2019
4. Muñoz M, et al. Exp Opin Drug Saf. 2018;17(2):149-59
5. Auerbach M, et al. Hematology Am Soc Hematol Educ Program. 2016;2016(1):57-66
6. Zeller MP, et al. CMAJ. 2017; 189(10):E409; Tolkien Z, et al. PLoS One. 2015; 10(2): e0117383
7. DeLoughery TG. Acta Haematol. 2019; 142(1):8-12
8. Auerbach M, et al. UpToDate. Last Updated July 2020
9. Muñoz M, et al. Anaesthesia. 2017;72(2):233-47