Ferroterapia en el manejo de la anemia en la enfermedad renal crónica no en diálisis: perspectiva del grupo de anemia de la S.E.N

This work presents an update on the management of iron deficiency in patients with chronic renal failure (CRF), either with or without anaemia. A review is made of the recommendations of the guidelines for the treatment of iron deficiency in CRF. It also presents new studies on iron deficiency in patients with CRF, as well as new findings about iron deficiency and its impact on clinical outcomes.Anaemia is a common complication of CRF, and is associated with a decrease in the quality of life of the patients, as well as an increase in morbidity and mortality. Iron deficiency (absolute or functional) is common in non-dialysis chronic renal failure patients, and may cause anaemia or a low response to erythropoiesis-stimulating agents. For this reason, the clinical guidelines for the treatment of the anaemia in Nephrology advise the correction of the deficiency in the presence of anaemia. Iron replacement therapy is indicated in patients with CRF and anaemia (Hb < 12 g/dL) in accordance with the guidelines. There is no unanimity in the indication of iron replacement therapy in patients with Hb>12 g/dL, regardless of whether they have an absolute or functional iron deficiency.Intravenous iron replacement therapy is safe, more efficient and rapid than oral therapy for achieving an increase haemoglobin levels and reducing the dose of erythropoiesis-stimulating agents. For the administration of intravenous iron in non-dialysis chronic renal failure patients a strategy of high doses and low frequency would be preferred on being more convenient for the patient, better conserving of the venous tree, and on being safe and cost-effective. Iron plays an essential role in energy metabolism and other body functions beyond the synthesis of haemoglobin synthesis, for which the iron deficiency, even in the absence of anaemia, could have a harmful effect in patients with CRF. The correction of the iron deficiency, in the absence of anaemia is associated with functional improvement in patients with heart failure, and in muscle function or fatigue in patients without CRF.Despite the evidence of benefits in the correction of iron deficiency in patients with CRF, more studies are required to evaluate the impact of the correction of the iron deficiency in the absence of anaemia on morbidity and mortality, quality of life and physical capacity, as well as the long-term effect of oral and intravenous iron replacement therapy in this population.     

A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia

Background

Clinically significant anaemia, requiring red blood cell transfusions, is frequently observed in Emergency Departments (ED). To optimise blood product use, we developed a clinical protocol for the management of iron-deficiency anaemia in a fast-track anaemia clinic within the ED.

Materials and methods

From November 2010 to January 2014, patients presenting with sub-acute, moderate-to-severe anaemia (haemoglobin [Hb] <11 g/dL) and confirmed or suspected iron deficiency were referred to the fast-track anaemia clinic. Those with absolute or functional iron deficiency were given intravenous (IV) ferric carboxymaltose 500–1,000 mg/week and were reassessed 4 weeks after receiving the total iron dose. The primary study outcome was the haematological response (Hb≥12 g/dL and/or Hb increment ≥2 g/dL). Changes in blood and iron parameters, transfusion rates and IV iron-related adverse drug effects were secondary outcomes.

Results

Two hundred and two anaemic patients with iron deficiency (150 women/52 men; mean age, 64 years) were managed in the fast-track anaemia clinic, and received a median IV iron dose of 1,500 mg (1,000–2,000 mg). Gastro-intestinal (44%) or gynaecological (26%) bleeding was the most frequent cause of the anaemia. At follow-up (183 patients), the mean Hb increment was 3.9±2.2 g/dL; 84% of patients were classified as responders and blood and iron parameters normalised in 90%. During follow-up, 35 (17%) patients needed transfusions (2 [range: 1–3] units per patient) because they had low Hb levels, symptoms of anaemia and/or were at risk. Eight mild and one moderate, self-limited adverse drug effects were witnessed.

Discussion

Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED.     

Fetal Hb Production during Acute Erythroid Expansion: I. OBSERVATIONS IN PATIENTS WITH TRANSIENT ERYTHROBLASTOPENIA AND POST-PHLEBOTOMY

In order to study fetal haemoglobin production during acute erythroid expansion we did sequential measurements of Hb F-containing erythrocytes (F-cells) and of relevant haematological parameters in 10 subjects recovering from eyrthroid aplasia, iron deficiency anaemia or following phlebotomy. An increased production of F-cells was consistently observed during the acute marrow expansion, but there were significant differences in the maximum F-cell response among individuals. These differences could not be explained by differences in the degree of anaemia alone, nor could they be correlated with the level of peak reticulocytosis. Two patients who reached the highest F-cell numbers were probably carriers of heterocellular hereditary persistence of Hb F, suggesting that this gene may play a role in determining the magnitude of F-cell production in anaemic patients. It is speculated that the main reason for the consistently observed increase in F cell production during acute marrow expansion is the premature terminal differentiation of earlier erythroid precursos (burst forming units; BFUe). This proposition is in accord with observations in vitro which suggest that Hb F is expressed en eyrthroid clones derived from BFUne's. It is further proposed that differences in the degree of BFUe recruitment may underly the disparities in Hb F response among individuals subjected to similar anaemic stimuli.     

Evaluation of erythroid marrow response to recombinant human erythropoietin in patients with cancer anaemia.

BACKGROUND. Anaemia is a frequent finding in patients with cancer and may be due to different causes, including blunted erythropoietin production. MATERIALS AND METHODS. In a pilot study, we administered recombinant human erythropoietin (rHuEPO) to twelve patients with solid tumours and secondary anaemia. rHuEPO was given subcutaneously 5 d per week at escalating doses (75 to 150 U/kg per day): the aim of treatment was a Hb level > or = 10 g/dl without blood transfusion. We evaluated endogenous EPO production through serum EPO levels and erythroid marrow activity by means of serum transferrin receptor (TfR). RESULTS. Six out of 12 subjects had defective endogenous EPO production. All patients but two responded to treatment with steady increases in Hb levels above 10 g/dl, and the median dose of rHuEPO required for correction of anaemia was 75 U/kg. Response was associated with an early increase in serum TfR. Six patients developed functional iron deficiency and required iron supplementation to obtain response. Treatment improved functional ability in 4/10 responders. CONCLUSIONS. Subcutaneous rHuEPO can stimulate erythroid marrow activity in cancer anaemia, even in patients with advanced disease, and marrow response can be adequately monitored by serum TfR. Functional iron deficiency as a cause of nonresponse to rHuEPO is frequent in these patients and may require parenteral iron administration. Although erythropoietin can improve the anaemia of cancer, the decision to treat should be individualised for each patient, looking more at the quality of life and cost-effectiveness than at cosmetic increases in the haemoglobin level.     

Molecular charge heterogeneity of human serum erythropoietin

The charge heterogeneity of human serum erythropoietin (S-Epo) was studied in 89 serum specimens from 78 subjects by zone electrophoresis in 0.17% agarose suspension at pH 8.6. The electrophoretic elution profiles of S-Epo were determined with a radioimmunoassay for Epo. The number of Epo peaks indicated that at least 20-30 different forms of Epo were present in a single serum specimen. The median charge of Epo, estimated as its median electrophoretic mobility, was determined for each serum specimen. This median charge was measured in 10 healthy adults, 46 patients with anaemia, six patients with secondary polycythaemia, one patient with polycythaemia vera treated by phlebotomy, and six healthy newborn infants (cord sera). Forty-four of the patients with anaemia had a median charge of S-Epo within the reference range for healthy adults, while all the patients with polycythaemia and the newborn infants had less negatively charged forms of S-Epo. In nine patients in whom the S-Epo level had a circadian rhythm, the forms of S-Epo in the evening were less negative than those in the morning. The median charge of recombinant preparations was much less negative than that of S-Epo in healthy individuals, while that of the 2nd International Reference Preparation was more negative than in any of the 78 subjects analysed. A significant change to less negatively charged S-Epo forms was observed 24 h after a subcutaneous injection of recombinant Epo in one patient, who before the injection had a normal median charge and concentration of S-Epo. In conclusion, Epo exhibits a considerable charge heterogeneity in individual serum specimens, the forms of S-Epo in the morning may differ from those in the evening, those in adults differ from those in newborn infants, and those in patients with anaemia differ from those in polycythaemia. The results also suggest that the methods used in this study may be useful for detecting the presence of injected recombinant Epo in the blood in persons with a normal endogenous Epo production.     

Anaemia in children following cardiac transplantation: treatment with low dose human recombinant erythropoietin.

Anaemia is common in children following cardiac transplantation. In a series of 5 children with anaemia beyond the immediate post-operative period one had a hypochromic, microcytic anaemia which corrected with oral iron. The other four had normochromic, normocytic anaemias unresponsive to iron or folate supplementation and associated with inappropriately low levels of erythropoietin. Subcutaneous administration of low dose human recombinant erythropoietin to these four patients resulted in correction of their anaemia. Our findings suggest that erythropoietin deficiency is an important cause of anaemia in transplant recipients and should be sought in cases of anaemia refractory to conventional haematinic therapy. In cases of proven erythropoietin deficiency, treatment with erythropoietin is effective, acceptable to patients and preferable to repeated blood transfusion.     

Prediction and evaluation of the effect of iron treatment in anaemic RA patients

Summary In order to predict a haemoglobin (Hb) rise, in response to treatment with iron from simple erythrocyte and serological parameters, we treated 28 anaemic RA patients with oral iron during 6 weeks. Iron deficiency, present in 57% of patients, was assessed by staining a bone marrow aspirate for iron. Response rate in this group was 81% and median Hb increase was 0.8 mmol/l. After 6 weeks 69% of iron deficient patients were still anaemic. Patients without iron deficiency, considered as having anaemia of chronic disease (ACD), showed no significant Hb rise. The finding of a hypochromic microcytic anaemia was associated with a significant Hb rise. MCV showed highest specificity and predictive value (90 and 88%) and ferritin was the most valid predictor of a Hb rise within 6 weeks. Combination of low MCV and low ferritin resulted in a 100% specificity and predictive value indicating that patients with values below cut off point of these variables will definitely respond to treatment. Disease activity tended to decrease after 6 weeks, but this was not correlated with a Hb rise. It was concluded that a Hb rise can be predicted accurately by blood parameters. Using certain combinations, bone marrow aspiration is rarely necessary. Iron treatment is only useful in iron deficient RA patients, although active RA limits maximal Hb rise. In contrast to earlier findings, iron treatment had no deleterious effects on disease activity.     

An analysis of the determinants of anaemia in pregnant women in rural Malawi--a basis for action.

Haematological data are presented on 4104 pregnant women attending the antenatal-care facilities of two hospitals in a rural area in southern Malawi. In this area, malaria transmission is perennial and there is a high prevalence of HIV infection. The local women are exposed to drought and food shortages but experience high fertility rates. Mean (S.D.) haemoglobin (Hb) concentration was significantly lower in the primigravidae [8.7 (1.60 g/dl] than in the secundigravidae [9.1 (1.5) g/dl; P < 0.0001] or multigravidae [9.2 (1.5) g/dl; P < 0.0001]. Primigravidae also experienced significantly more iron deficiency and malaria than secundi- or multi-gravidae. For all parity groups, the lowest mean Hb levels were observed between 26-30 weeks' gestation. In primigravidae peak prevalence of malaria occurred between 16-20 weeks' gestation (38.6%) and peak prevalence of moderately severe anaemia (< 8 g Hb/dl) between 26-30 weeks' (35.7%). Multigravidae showed little variation in the prevalence of anaemia, iron deficiency and malaria with gestational age. Peak prevalences of malaria were observed in April, in the post-rainy season, with values of 51.4%, 56.0% and 25.3% for primi-, secundi- and multi-gravidae, respectively. Peak prevalences of iron deficiency occurred between April and May and those of moderately severe anaemia between May and June. Mean Hb was lower in adolescent primigravidae than in any other group of pregnant women [8.6 (1.5) g/dl], including the non-adolescent primigravidae [8.9 (1.6) g/dl; P = 0.008]. Other factors significantly associated with increased risk of moderately severe anaemia in primigravidae were illiteracy and poor nutritional status (i.e. body mass index < 18.5 kg/m2 and mid-upper-arm circumference < 23 cm). After forward, step-wise, regression analysis of relative risk (RR) factors and their 95% confidence intervals (CI), variables associated with an increased risk for moderately severe anaemia were iron deficiency (RR = 4.2; CI = 3.0-6.0) and malaria parasitaemia (RR = 1.9; CI = 1.3-2.7) in primigravidae, iron deficiency (RR = 4.1; CI = 2.7-6.3) and mid-upper-arm-circumference < 23 cm (RR = 1.8; CI = 1.1-3.0) in secundigravidae, and iron deficiency in multigravidae (RR = 3.1; CI = 4.3-6.9).     

Plasma Iron and Erythrocytic Glutathione Peroxidase Activity

The red cell glutathione-peroxidase (GSH-Px) activity of 9 normal subjects is compared with that of 15 cases of iron deficiency anaemia and with 13 cases of heterozygous beta-thalassaemia with the same degree of anaemia and hypochromia. 2 cases of sideroblastic anaemia with high serum iron levels were also examined. Enzymatic activity was found to be significantly decreased in iron deficiency anaemia (about 55 % of normal range), while it was not affected in heterozygous betathalassaemia and it was increased in the 2 cases of sideroblastic anaemia. Moreover, GSH-Px activity exhibited a significant correlation with serum iron levels in all the patients studied. The observed modifications in GSH-Px activity are not correlated with erythrocyte ageing because reticulocyte-poor fractions exhibited GSH-Px activity which was not significantly reduced in respect of the reticulocyte-rich ones. These data seem to suggest that iron has a crucial connection with erythrocyte GSH-Px and that the enzyme deficiency may be of some importance in explaining the decreased red cell survival observed in severe iron-deficiency anaemias.     

Sickle-Cell Anaemia in Turkey Evaluation of 97 Cases (with Parents' Findings)

The haematological and clinical data in 97 sickle-cell anaemia cases and haemato-logical findings of their parents are reported. In spite of the low Hb values of the patients, they tolerated their anaemia and very rarely required blood transfusions. The Hb F levels of the patients were in general higher than African origin SS anaemia patients but lower than the Shiite Saudi Arabians. However, in most of the cases the concentration of Hb F did not seem to influence the Hb concentration of the patients. Serum iron was found unexpectedly decreased in 22 % of the patients. Osmotic fragility was found decreased in 100 % of the patients and in 83.5 % of the parents. The prevalence of G-6-PD deficiency was 21.2 % in male patients and 15.6 % in the parents.     

Reduced Frequency of Iron Deficiency Anaemia in Sickle Cell Trait

The prevalence and causes of anaemia among the inhabitants of a Southern Lebanese village were studied. Of the 317 patients examined 75, or 24% were found to be heterozygotes for Hb S. There was a reciprocal relation between the presence of sickle cell trait and of iron deficiency anaemia. The prevalence of iron deficiency anaemia defined as the coexistence of Hb below 13 g/dl in adult males and below 12 in adult females and children with two laboratory indicators of iron deficiency, was 10.3 % in the normal population as against 1.3 % in the sickle cell trait group (P < 0.008). The reduced frequency of iron deficiency anaemia in sickle cell trait may be explained by increased iron absorption, or alternatively by reduced iron requirements and a lower risk of discrepancy between iron supply and demand. Because of the central role of iron in the function of a great number of enzymes and proteins, it is possible that protection against iron deficiency anaemia by the sickle cell trait may result in improved working capacity and a lower incidence of infections.     

Serum soluble transferrin receptor in the diagnosis of iron deficiency in chronic liver disease

Fifty-one consecutive patients with chronic liver disease (CLD) underwent investigations of their iron status (full blood count, serum iron [Fe], total iron binding capacity [TIBC], transferrin saturation [TS], serum ferritin and serum soluble transferrin receptor [sTfR] level). Twenty-six patients were anaemic; 12 patients had iron deficiency, and 10 had iron deficiency anaemia (IDA). The median (range) sTfR in the IDA patients was 16.6 (11.2–24.8) mg/l, compared with 6.6 mg/l (11.2–24.8) in the 16 patients with anaemia due to other causes (P = 0.01). The sensitivity of sTfR for diagnosing iron deficiency in CLD was 91.6% (100% if only anaemic patients are included) and the specificity was 84.6%. Patients with haemolysis and recent blood loss may have falsely elevated sTfR levels. The results suggest that the sTfR is as useful as serum ferritin in identifying a potentially treatable cause of anaemia in CLD.     

Serum erythropoietin levels in paroxysmal nocturnal haemoglobinuria: implications for therapy

In order to assess the rationale and possible indications for the use of recombinant erythropoietin in paroxysmal nocturnal haemoglobinuria (PNH), we have measured endogenous erythropoietin (Epo) levels in 18 patients with PNH and in 44 patients with iron deficiency anaemia (IDA). In both groups of patients we found a significant inverse correlation between Epo and haemoglobin (Hb). However, the mean Epo level was significantly higher in the PNH group (385 mU/ml) than in the IDA group (136 mU/ml). The range of Epo levels at any given Hb was greater in the PNH group than in the IDA group. There was a significant positive correlation between Epo and absolute reticulocyte count. Since Epo administration is unlikely to benefit patients with high levels of endogenous Epo, we conclude that in the majority of patients with PNH there is no indication for treatment with Epo.     

Iron status of Zairean pregnant women with and without serological markers of hepatitis B virus infection

We assessed the iron status of 203 Zairean pregnant women: 38 with chronic hepatitis B virus (HBV) infection (HBsAg(+)), 94 with antibodies to the surface antigen (Anti-HBs(+)) and 71 without HBV markers (HBsAg(-)/Anti-HBs(-)). Participants, age range 15-42 years and parity 1-12, were recruited from Mama Yemo Hospital in summer 1983. Haemoglobin (Hb), serum iron, total iron binding capacity and transferrin saturation (TS) were determined by standard techniques and serum ferritin (FERR) by radioimmunoassay. To rule out inflammation and/or infection which increase FERR levels, C-reactive protein (CRP) and alpha 1-acid glycoprotein (AGP) were also measured. There was no significant difference in the mean levels of any of the haematologic measurements, FERR, CRP and AGP between the three HBV groups. Women who took iron supplements had slightly higher mean levels of Hb but not serum FERR or TS than those who did not. Women with inflammation and identical HBV markers had higher mean FERR levels than those without inflammation. Neither the prevalence of anaemia, which varied between 32 and 35%, nor that of iron deficiency, which varied between 52 and 59%, differed significantly between the three groups of women. We conclude that in pregnant women, chronic asymptomatic HBV infection is not associated with a lower prevalence of iron deficiency and/or anaemia.     

Functional erythropoietin deficiency in patients with Type 2 diabetes and anaemia.

AIMS: Anaemia is a common finding in patients with diabetic nephropathy. Impaired production of erythropoietin is thought to be the predominant cause, as a result of renal microvascular disease. This study aims to determine the prevalence of functional erythropoietin deficiency in a cross-sectional survey of patients with Type 2 diabetes. METHODS: Clinical data on 604 patients with Type 2 diabetes were obtained, including a full blood count, iron indices and detailed history of diabetic complications. Erythropoietin levels were correlated with the presence of anaemia, iron deficiency and renal dysfunction. Functional erythropoietin deficiency was defined by erythropoietin levels in the normal range despite the presence of anaemia. RESULTS: Nineteen per cent of patients (n = 112) were anaemic, among whom erythropoietin deficiency (76%) and reduced iron availability (58%) were common findings. Over 90% of patients had erythropoietin deficiency, once those with reduced iron stores or availability were excluded. Most of these patients had moderate renal impairment (60%, n = 67). However, even in the absence of renal impairment, 71% of anaemic patients (n = 32/45) had functional erythropoietin deficiency, although most had other evidence of nephropathy. In addition, two-thirds of patients with reduced iron availability were unable to increase erythropoietin above the normal range. CONCLUSIONS: These findings confirm the failure of the kidney to produce erythropoietin in response to a falling haemoglobin is a key component to anaemia in diabetes. The likelihood of functional erythropoietin deficiency as a cause of anaemia is not dependent on the severity of renal impairment or excluded in diabetic patients with reduced iron stores or availability.     

Total dose infusion of intravenous iron in patients with chronic kidney disease receiving haemodialysis

A regimen of a single high dose iron administration was initially adopted for patients commencing haemodialysis (HD) treatment. Iron stores are established and iron metabolism and erythropoiesis stabilise allowing haematinic parameters to be more confidently assessed for use in anaemia management decisions. High doses of IV iron delay the need for subsequent iron supplementation. A high-dose, low-frequency iron infusion regimen for all HD patients was adopted. The outcomes of administering this dosage regimen are reported as observational retrospective analysis using patient record data in 2009. Patients received three [median; semi-interquartile range (SIQR) 0.5] high-dose iron infusions during the year. The median infusion dose was 1100 mg iron (SIQR 0.0) and the median amount of iron received during the year by each patient was 3200 mg (SIQR 750). The median haemoglobin (Hb) level prior to infusion was 108 g/l and post infusion 114 g/l; ZHb = 2.656, p = 0.008). Ferritin levels increased from a median of 376 μg/l preinfusion to 690 μg/l postinfusion; Zferritin =-4.796, p < 0.001. The median time between infusions was 125 days (approximately four months). The 51 patients (76%) who received three or less infusions within the study period received 2537 mg (mean) of iron. These findings indicate that both Hb and ferritin levels can be adequately managed using a high-dose, low-frequency regimen of IV iron in patients undergoing HD.     

Anaemia in acute, Plasmodium falciparum malaria in children from Orissa state, India.

The severity of anaemia associated with acute, Plasmodium falciparum malaria and the extent to which haemolysis, bone-marrow suppression, and pre-existent iron deficiency contribute to the anaemia were assessed in 102 Indian children aged 2-12 years. Blood haemoglobin (Hb), plasma unconjugated bilirubin and haptoglobin, serum iron and transferrin concentrations and transferrin saturation, red cell morphology and reticulocyte response were investigated in the patients and in 50 control children. Twenty-three patients with severe anaemia (< 70 g Hb/litre) were investigated further, by bone-marrow biopsy followed by iron staining of sections or touch smears of the biopsy material. There was evidence of haemolysis in the malaria cases: in the peripheral blood smears and the significantly higher plasma concentrations of unconjugated bilirubin, lower plasma concentrations of haptoglobin and lower blood concentrations of Hb than those seen in the controls. Haemoglobin concentration correlated directly with haptoglobin (r = 0.489; P < 0.001) and inversely with unconjugated bilirubin in malaria patients (r = -0.526; P < 0.001) but not in controls (r = -0.140 and -0.061, respectively). Parasitaemia (parasites/microliter) was not significantly correlated with Hb, haptoglobin or unconjugated bilirubin. Compared with the earlier samples, follow-up samples from the patients, collected 2 weeks after discharge from hospital and antimalarial therapy, showed significant increase in Hb, haematocrit, haptoglobin and decreases in both total and unconjugated bilirubin. There was evidence of hypercellularity and mild-moderate erythroid hyperplasia, mainly of normoblastic maturation with adequate reticulocyte response, in the bone-marrow samples from the cases of severe anaemia; dyserythropoiesis was only noticed in one case and no stainable iron was detectable in 17 of the 23 cases. These observations indicate that haemolysis is the prime cause of the anaemia seen in acute falciparum malaria, although destruction of parasitised erythrocytes is not the sole cause of the haemolytic process. Bone-marrow suppression appears to have an insignificant role but pre-existent iron deficiency aggravates the severity of the anaemia.     

Serum erythropoietin in patients with myelofibrosis with myeloid metaplasia

Summary. Serum erythropoietin levels (s-Epo) were measured by radioimmunoassay in 61 consecutive anaemic patients (Hb<12 g/dl) with myelofibrosis with myeloid metaplasia (MMM). S-Epo was inversely correlated with Hb (r= -0.48, P <0.0001). When observed s-Epo values were compared with predicted levels based on the relationship between s-Epo and Hb in control subjects, all but eight patients (87%) had s-Epo levels appropriate for the degree of anaemia. The observed/predicted (O/P) s-Epo ratio was significantly lower in patients with signs of active disease, and a significant inverse correlation was found between the O/P ratio and erythrokinetic measurement of the extent of erythropoiesis (r=0.31; P =0.02). Circulating Epo levels were appropriate for the variations in Hb during the postsplenectomy period in three patients. In conclusion, this study does not support the idea that therapy with erythropoietin should be extensively used in anaemic patients with MMM, but rather that it should be considered only in selected cases.     

Marked erythropoietin increase before fall in Hb after treatment with cytostatic drugs suggests mechanism other than anaemia for stimulation

Serum erythropoietin (Epo) was measured in 23 patients before, during and after intensive cytostatic treatment courses for acute leukaemia or before bone marrow transplantation. A marked increase was seen in all patients, starting 1 or 2 d after initiation of treatment. A peak was reached after about 7 d, at levels as high as 1450 IU/l, after which Epo fell rapidly, even in patients who were anaemic at that time. In 13 of the patients there was no fall in Hb level that could explain the increase in Epo. The increase was too large to be explained by an altered Epo metabolism or marrow utilization. Cytostatic drugs cause an increase in Epo production not mediated through anaemia, possibly initiated by a cytostatic effect on the kidneys or by an unknown stimulatory factor, responsive to bone marrow inhibition.     

Improved preoperative iron status assessment by soluble transferrin receptor in elderly patients undergoing knee and hip replacement

A poor preoperative haemoglobin (Hb) status is frequently encountered among adult patients scheduled for corrective surgery of the locomotive system, representing the main risk factor for blood transfusion. The soluble transferrin receptor (sTfR) has become a highly specific parameter for the detection of iron deficits as it can differentiate between iron deficiency anaemia and anaemia of chronic disease, because of the lack of effect by associated inflammation, unlike ferritin. The objectives of this study were to evaluate patients with the prevalence of risk for transfusion, the effect of inflammation on ferritin (F) values and functional iron deficiency in elderly patients with advanced degenerative arthropathy scheduled for hip or knee replacement. This observational, prospective study included patients over 50 years, operated for hip or knee replacements between April and June 2004. Of 218 patients studied, 87 (39%) presented with Hb levels between 10 and 13 g/dl. The prevalence of functional iron deficit was 27% (sTfR > 1.76 mg/l), while only 8.6% of patients displayed F levels below normal. As expected, C-reactive protein levels were elevated in 24.8% of patients and erythrocyte sedimentation rate was elevated in 50%. These inflammatory markers did not correlate with levels of either F or sTfR. Multiple factors can affect F levels, such as the inflammatory status of osteoarthritis in the elderly, obesity, nonsteroidal anti-inflammatory drugs therapy and low physical performance. As sTfR is not affected by inflammation, it has emerged as a primary parameter for the evaluation of iron status during preoperative assessment among patients scheduled for arthroplasty surgery. Our data strongly suggest that sTfR measurement contributes to improve patient management.