Iron Therapy in Patients With Heart Failure and Iron Deficiency

Review of Iron Preparations for Practitioners

Marcin Drozd; Ewa A. Jankowska; Waldemar Banasiak; Piotr Ponikowski

Disclosures

Am J Cardiovasc Drugs. 2017;17(3):183-201. 

In This Article

Assessment of ID

Bone marrow aspiration is the most accurate method to assess iron status,[27–31] but this examination is invasive, not widely available, and unsuitable for assessing ID in daily clinical practice. Laboratory blood tests are therefore the preferred method to diagnose and monitor ID.

Circulating ferritin is a reliable indicator of iron stores. The primary tissues where iron is physiologically stored are reticuloendothelial cells within bone marrow, liver and spleen. A ferritin level of <100 μg/L is considered to reflect an absolute ID in HF. Lower values of ferritin correlate with more depleted iron stores. In the general population, the cut-off of serum ferritin to diagnose absolute ID is usually 30 μg/L,[31,32] although lower values (i.e. 12–15 μg/L) have also been applied.[33,34] Importantly, ferritin is an acute phase reactant, and its level is increased in the state of inflammation.[35–41] Therefore, in chronic disease accompanied by inflammation (e.g. HF), when diagnosing ID, higher cut-off values of ferritin should be used (100 μg/L).[15,30,42]

The second type of ID is functional ID (or relative ID), in the course of which the availability of iron for metabolic processes is restricted despite preserved iron stores. Functional ID is characterized by low transferrin saturation (TSAT). TSAT reflects the percentage of transferrin with in-bound iron and is calculated as the ratio of serum iron and total iron-binding capacity by transferrin (TIBC), and direct transferrin measurement is not necessary.[15] Transferrin may be elevated in the setting of inflammation, which indicates lower TSAT if circulating iron is constant. On the other hand, low circulating transferrin (accompanying malnutrition in the course of chronic inflammatory disease) can result in an artificially increased TSAT.

The accepted criteria for detecting ID in patients with HF are serum ferritin <100 μg/L defined as absolute ID, or serum ferritin 100–300 μg/L in combination with a TSAT of <20% defined as functional ID.[13,15,43] This definition was previously applied in CKD[42] and further adapted in HF studies.[12,13] Importantly, neither serum iron nor serum transferrin alone should be analysed as biomarkers of iron status. It needs to be acknowledged that there are attempts to develop more precise definitions of ID based on experimental biomarkers, e.g. the combined assessment of serum hepcidin (correlates with iron stores more precisely than ferritin) and soluble transferrin receptor (sTfR) (facilitates intracellular import of iron; ID induces the expression and release of the transferrin receptor to the circulation).[32,37,44]

In patients with iron deficiency anaemia (IDA), we need to exclude other causes than ID before initiation of iron therapy. The physician should include the following in the anamnesis and diagnostic process: dietary history, to identify poor iron intake; history of blood donations; use of NSAIDs; inherited disorders of iron absorption (i.e. coeliac disease); haematological disorders; impaired renal and liver function; and bleeding (e.g. digestive). The diagnosis of ID in patients without anaemia usually does not require further investigation, and iron therapy can be initiated immediately.

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