Iron deficiency anaemia

IDA

 

Ferritin: (BSG 2021 / UTD)

 

Ferritin is the universal intracellular protein containing Iron – a soluble and non-toxic form. It is the primary iron storage protein in prokaryotes and eukaryotes. Ferritin w/o iron is called apo-ferritin. Each ferritin molecule can store up to 4,500 atoms of iron within it.

 

 

Iron deficiency anaemia:

 

1)    Low MCH is more sensitive for Iron deficiency than Low MCV.

2)    Low Ferritin is single most important serological marker of IDA. Serum ferritin assessed by assays is usually apo-ferritin, but reflects intra-cellular ferritin stores in RES (macrophages in liver, spleen, LN etc) in absence of inflammation.

 

Fe < 15 – indicative of absent iron stores

Fe <45 – indicative of low iron stores

 

In anaemia of chronic disease / CHF  - TSat <20% with Fe <100 is suggestive of Fe deficiency

 

 

Fe > 150 unlikely to represent low iron stores even in face of inflammation.

 

3)    Transferrin Sat is generally low in IDA. Keep in mind that Tsat is (iron/TIBC x100) – therefore levels may falsely go up with high Serum iron (soon after oral replacement for eg).

Tsat <10% is  highly suggestive of IDA

Tsat < 20%

 

 

Special population:

·      RYGB predisposes to Fe deficiency (25% prevalence after 2 years)

·      Sleeve gastrectomy / atrophic gastritis / PPI also cause impaired iron absorption

 

 

Concept of Functional Iron deficiency (poor Fe mobilisation)

 

Key concept – Hepcidin is a protecin secreted by liver, which inhibits Ferroportin. Ferroportin is present on basolateral membrane of enterocytes (facilitates transfer of Fe from enteric lumen in to blood), and on Macrophages (for mobilisation of Fe to the marrow for erytheopoesis).

 

In chronic diseases, CHF, CKD – High hepcidin levels, not only results in poor gut-absorption of Iron, but also makes iron mobilisation from macrophages difficult.

 

In haemochromatosis, HFE protein ultimately inhibits secretion of Hepcidin from hepatocytes, which leads to persistent high absorption of Iron from Gut.

Key concepts: Iron stores

 

Hb contains usually ~ 2 g of Iron

REC (macrophages) contain 400 – 500 mg Fe in females, and 800 mg – 1g in males (for erythropoiesis)

Daily absorption and losses of Iron in non-anaemic people is 1-2 mg / day

·      1 unit of pRBC contains ~ 200 mg of Iron. To replete iron stores in anaemics, 1-2g of IV iron is required in total (based on Hb etc).

·      Usually 1-2g IV Fe replacement is adequate to replenish iron stores.

 

 

 

 

Oral Iron replacement therapy

·      Oral Fe must be taken on empty stomach – 75% reduced bioavailability if taken w food

·      Vit C does not improve Fe absorption or reduce intolerance (RCT)

·      Following enteral Iron, Hepcidin levels rise for next 24 hours, significantly reducing subsequent iron absorption. Therefore, multiple daily dosing is ineffective, and alternate day dosing is superior to daily dosing.

 

·      BSG recommendation dose: 50-100 mg elemental iron daily

 

 

 

Par-enteral iron replacement therapy

·      For patients with GI intolerance to oral iron, or inadequate Hb incrementation, parenteral Fe to be considered

·      CHF – parenteral iron may be preferred (Gut oedema, raised hepcidin) likely makes gut absorption ineffective

·      Anaemia of chronic disease (inflammation) – for reasons similar to CKD, parenteral may be preferred. No concrete guidelines, can try oral first and wait for it to fail.

 

Hypophosphataemia is due to molecules complexed to IV iron, more common with Ferric carboxymaltose (Ferrinject) (upto 58%), generally mild-mod and asymptomatic and doesn’t require supplementation.

 

 

CKD –

·      CKD contributes to anaemia (with low erythropoietin) once eGFR is <60, and significant effect once eGFR is <30.

·      Par-eneteral iron is preferred (High hepcidin due to inability of failing kidneys to excrete reduces enteral absorption).

·      In CKD (non-HD), keep Fe >100, in HD patients, keep Fe >200.

 

 

After trial of iron replacement therapy

·      Hb increments by 10g/l two weeks after initiation of IRT (oral or IV)

·      Retic-Hb rises on day 4 onwards

 

 

 

10.1016/j.amjmed.2005.01.065 – trial of 15mg, 50mg and 150mg of elemental daily iron supplement in patients > 80 years of age with IDA – similar increment in Hb & Fe!