Soluble Transferrin Receptor (sTfR)

Cells that need iron, especially the precursors of red blood cells in the bone marrow, take up iron through the transferrin receptor on their surface. If they have too little iron, they make more receptors; some of these end up loose in the blood as soluble transferrin receptor (sTfR). The value therefore rises with iron deficiency at the cell level and with increased production of red blood cells. Unlike ferritin, sTfR hardly rises during inflammation.

• Iron deficiency at the cell level, even if ferritin looks normal due to inflammation
• The distinction between anemia due to iron deficiency and anemia due to a chronic illness or inflammation
• Increased production of red blood cells, for example when red blood cells are being broken down

With a raised value, the GP assesses the result together with hemoglobin, ferritin, CRP and the blood count. If the result fits iron deficiency, the GP looks for the cause, such as blood loss or reduced absorption, and usually starts iron supplements. If the cause is unclear or there are signs of breakdown of red blood cells, referral to an internist (specialist in internal medicine) follows.

sTfR is a well-studied addition for one specific question: distinguishing whether anemia in someone with inflammation or a chronic illness is (partly) caused by iron deficiency. According to the Dutch GP guideline (NHG) on anemia, ferritin, together with CRP if needed, tells you the most about iron status; sTfR is mainly an addition if ferritin is hard to interpret because of inflammation. There are no agreed cut-off values for sTfR: the measurement methods are not standardized, so results and cut-off values differ greatly between laboratories. In someone without anemia and without inflammation, the result adds little to ferritin.

• Increased production of red blood cells (hemolysis, thalassemia, after bleeding, at high altitude, EPO) raises the value without iron deficiency.
• Reduced production in the bone marrow, for example with severe kidney damage, lowers the value and can mask iron deficiency.
• The measurement methods are not standardized; results from different laboratories are not comparable.
• Pregnancy raises the value because of the increased production of red blood cells.

Anemia is newly diagnosed in general practice in about 8 to 9 in 1000 people per year, more often in women; in about half of them it is due to iron deficiency. Anemia due to a chronic illness or inflammation is the second most common form, especially in older people.

The result is mainly meaningful with anemia in which ferritin is hard to interpret, such as with inflammation, infection, rheumatic disease, kidney disease or another chronic illness. In people without anemia and without inflammation, ferritin usually tells enough and sTfR adds little.

• A rise due to increased production of red blood cells can wrongly be read as iron deficiency.
• Because cut-off values differ between laboratories, a result can be misinterpreted if it is compared with one from another laboratory.

• NHG-Standaard Anemie (M76)
• NVKC, allesovertesten.nl: Ferritine
• NVKC, allesovertesten.nl: Transferrine