Transferrin saturation

Determinations of plasma Iron, total Iron-binding capacity (TIBC), and % transferrin saturation... 

Decreased red blood cell (RBC) count, hemoglobin (Hgb) and hematocrit (Hct) iron metabolism may also be altered [iron level, total iron binding capacity (TIBC), serum ferritin level, and transferrin saturation (TSAT)]. Erythropoietin levels are not routinely monitored and are generally normal to low. Urine positive for albumin or protein. 

Transferrin saturation (serum iron/TIBC)—indicates the amount of transferrin that is bound with iron it is lower in iron-deficiency anemia. 

Transferrin saturation (TSAT) Other Tests 30-50% (0.30-0.50) Transferrin saturation = (serum iron/TIBC) x 100 a saturation of less than 15% is common in iron-deficiency anemia. 

Although EPO deficiency is the primary cause of CKD anemia, iron deficiency is often present, and it is essential to assess and monitor the CKD patient s iron status (NKF-K/DOQI guidelines). Iron stores in patients with CKD should be maintained so that transferrin saturation (TSAT) is greater than 20% and serum ferritin is greater than 100 ng/mL (100 mcg/L or 225 pmol/L). If iron stores are not maintained appropriately, epoetin or darbepoetin will not be effective, and most CKD patients will require iron supplementation. Oral iron therapy can be used, but it is often ineffective, particularly in CKD patients on dialysis. Therefore, intravenous iron therapy is used extensively in these patients. Details of the pharmacology, pharmacokinetics, adverse effects, interactions, dose, and administration of erythropoietin and iron products have been discussed previously. 

The situation prevailing in the crypt cell at the beginning of its differentiation into an enterocyte and before it has begun to climb towards the villus is shown in the lower panel. The cell s iron requirements are supplied by receptor-mediated diferric transferrin uptake from the basolateral membrane. The TfR in turn is involved in an interaction with the HFE protein, which decreases the affinity of TfR for diferric transferrin. The level of transferrin saturation, or some other factor, determines the amount of iron taken up, and presets the IRP system at a level that corresponds to the iron requirements of the organism. 

The earliest and most sensitive laboratory change for iron-deficiency anemia is decreased serum ferritin (storage iron), which should be interpreted in conjunction with decreased transferrin saturation and increased total iron-binding capacity (TIBC). Hb, hematocrit, and RBC indices usually remain normal until later stages of iron-deficiency anemia. 

Iron indices (transferrin saturation [TSat] ferritin) should be evaluated before initiating an erythropoietic agent (see Fig. 76-5). To avoid errors, clinicians should wait at least 2 weeks after a loading dose of IV iron to reassess iron indices. 

FIGURE 76-5. Guidelines for iron therapy in the management of the anemia of chronic kidney disease (CKD). (CHr, content of hemoglobin in the reticulocytes ESA, erythropoietic-stimulating agent Hb, hemoglobin HD, hemodialysis PD, peritoneal dialysis TSat transferrin saturation.)... 

Monitoring Exercise caution to withhold iron administration in the presence of evidence of tissue iron overload. Periodically monitor hematologic and hematinic parameters (hemoglobin, hematocrit, serum ferritin, and transferrin saturation). Withhold iron therapy in patients with evidence of iron overload. Transferrin saturation values increase rapidly after IV administration of iron sucrose thus, serum iron values may be reliably obtained 48 hours after IV dosing. 

Pretherapy iron evaluation - Prior to and during therapy, evaluate the patient s iron stores, including transferrin saturation and serum ferritin. Transferrin saturation should be at least 20% and ferritin should be at least 100 ng/mL. Virtually all patients will eventually require supplemental iron (see Precautions). Adequately... 

Functional iron deficiency may develop with normal ferritin levels but low transferrin saturation (less than 20%), presumably due to the inability to mobilize iron stores rapidly enough to support increased erythropoiesis. Underlying infectious, inflammatory, or malignant processes. 

Serum ferritin, transferrin saturation supplemental iron recommended if ferritin <100 mcg/L or transferrin saturation <20%... 

For patients who are treated chronically with parenteral iron, it is important to monitor iron storage levels to avoid the serious toxicity associated with iron overload. Unlike oral iron therapy, which is subject to the regulatory mechanism provided by the intestinal uptake system, parenteral administration, which bypasses this regulatory system, can deliver more iron than can be safely stored. Iron stores can be estimated on the basis of serum concentrations of ferritin and the transferrin saturation, which is the ratio of the total serum iron concentration to the total iron-binding capacity ( ). 

On further testing, the patient displayed the biochemical signs of iron overload. He had a serum iron of 197 mg/dL (reference 30-360 pg/dL), a total iron binding capacity of 202 pg/dL (reference 228-428 pg/dL), and a ferritin level of 4890 ng/mL (reference 30-300 ng/mL). His serum transferrin saturation was calculated to be 97.5% (reference 20%-50%). 

The diagnosis of HH is established based on serum transferrin saturation (TS), defined as serum iron divided by total iron binding capacity (TIBC). Since serum iron and ferritin levels lack specificity for diagnosis when used alone, measurement of fasting TS is currendy recommended as a first screen to detect iron overload. TS is the best indirect biochemical marker of iron stores. A fasting TS of greater than 45% will detect over 98% of all cases of phenotypic hemochromatosis (Tavill, 2001). 

In 1998, Zhou and colleagues used an HFE knockout mouse model to elegantly bring together the pathophysiological and molecular aspects of the disease. Even when fed a standard diet, the knockout mice showed abnormally high transferrin saturations and excessive iron deposition in the liver and passed these traits on in an autosomally recessive manner. 

Iron status should be evaluated prior to and during treatment and iron supplementation administered if necessary. Patients receiving ESA maintenance therapy should be given iron supplements to keep their serum ferritin between 200 and 500 micrograms/L in both haemodialysis patients and non-haemodialysis patients, and either the transferrin saturation level above 20% (unless ferritin >800 micrograms /L) or percentage hypochromic red cells (%HRC) less than 6% (unless ferritin >800 micrograms/L). In practice it is likely this will require intravenous iron. 

The lanthanides modify the UV absorption spectra of proteins when aromatic chro-mophores are present at the binding site. Sharp maxima at 245 and 295 nm in the difference spectrum of transferrin saturated with Tb3+ ion as opposed to that of metal free protein were observed [20]. The shape of the spectrum is suggestive of lanthanide induced... 

The diagnosis of iron deficiency has its difficulties and ambiguities. Severe iron deficiency can be detected easily by the marked reduction in hemoglobin concentration, mean corpuscular hemoglobin and decreased serum iron concentration. However, in mild iron deficiency hemoglobin concentration, transferrin saturation, and serum ferritin levels are frequently normal in patients with depleted bone... 

Transferrin A high-affinity serum iron transport protein Transferrin is synthesised in the liver and its levels are diminished in cirrhosis Iron overload i.e haemochromatosis/haemosiderosis may lead to cirrhosis. A transferrin saturation >55% in males (and postmenopausal women) or >50% in premenopausal women requires investigation to exclude a diagnosis of hereditary haemochromatosis... 

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