Allan Rajamäki

Single values of serum transferrin receptor and transferrin receptor ferritin index can be used to detect true and functional iron deficiency in rheumatoid arthritis patients with anemia

OBJECTIVE To elucidate the use of serum transferrin receptor (sTfR) to distinguish between iron-deficiency anemia (IDA) and anemia of chronic disease (ACD), and to establish an improved scheme to identify functional iron deficiency (FID) in rheumatoid arthritis (RA) patients with anemia. METHODS We studied 30 anemic RA patients whose iron status was confirmed by bone marrow examination and determination of the sTfR level, serum ferritin level, and sTfR-log ferritin index (TfR-F Index). All patients with diminished or exhausted iron stores (n = 18) received oral iron supplementation. RESULTS Baseline values of sTfR and the TfR-F Index predicted the response correctly in all patients who received supplementation treatment and were normal in 10 of 11 patients with normal initial iron stores (ACD). CONCLUSION The results of this study elucidate the roles of sTfR and the TfR-F Index in the differential diagnosis between IDA and ACD and provide direct evidence that these parameters are useful in detecting FID, irrespective of the concurrent iron storage status.

SERUM TRANSFERRIN RECEPTOR, FERRITIN AND TFR-F INDEX IN IDENTIFICATION OF LATENT IRON DEFICIENCY

To the Editor: Iron delivery to erythroblasts is mediated by the interaction of transferrin with cell surface transferrin receptor (TfR), and TfR expression is induced by a decrease in the level of intracellular free iron. Soluble TfR in plasma is a truncated form of the tissue receptor (1). The bulk of TfR in human body is in the erythroid precursors in bone marrow and, therefore, not only the iron status but also the total mass of erythropoesis has a considerable effect on the concentration of soluble TfR in plasma. An increase in serum TfR concentration is a reliable indicator of depletion of iron stores, and it has become apparent that TfR measurements might also aid patient care when differential diagnosis between iron-deficiency anemia and anemia of chronic disease is required (2-4). Importantly, unlike serum iron, transferrin or ferritin, serum TfR seems not to be considerably influenced by the acute phase responses (4-7). A special challenge for the various laboratory tests of iron status is the identification of the so-called latent iron deficiency that is the identification of patients with depleted iron stores when the hemoglobin concentration is still within the reference range. Diagnosis of latent iron-deficiency may be desired in patients whose hemoglobin concentration has decreased to a level close to the lower reference limit, and who at the same time have modest microcytic changes in red cells (8). People who frequently donate blood as well as pure vegetarians constitute groups in which iron deficiency can be presumed to be more frequent than in the overall population (9, 10). The importance of a proper diagnostic basis for the use of oral iron supplementation has been further emphasized by recent studies in which a positive correlation between body iron stores and, e.g., the risk of coronary heart disease has been reported

Simultaneous quantitative analysis of FcγRI (CD64) and CR1 (CD35) on neutrophils in distinguishing between bacterial infections, viral infections, and inflammatory diseases

A flow cytometric quantitative analysis of receptors on neutrophils can be exploited in distinguishing between inflammatory and infectious diseases. In this prospective comparative study, simultaneous quantitative analysis of CD64 and CD35 on peripheral blood neutrophils was performed in febrile patients in order to differentiate between bacterial infections (n=89), viral infections (n=46), and inflammatory diseases (n=21). The patient data was compared to 60 healthy controls. We could divide patients into three groups depending on how they express CD35 and CD64 on neutrophils: (1) patients with a high probability of viral infection (low CD35/low CD64 and low CD35/high CD64), (2) patients with a high probability of inflammatory disease (high CD35/low CD64), and (3) patients with a high probability of bacterial infection (high CD35/high CD64). In summary, simultaneous quantitative analysis of CD64 and CD35 on neutrophils could potentially assist physicians to distinguish between inflammatory and infectious diseases.

Hematological parameters in preterm infants from birth to 16 weeks of age with reference to iron balance

Abstract Background: The objective of this study was to describe the natural kinetics of serum soluble transferrin receptor (S-TfR), ferritin and reticulocyte indices in preterm neonates, and to find out whether these analytes relate to hematocrit (Hct) level in determining the need for red cell (RBC) transfusions. Methods: During a 2-year period, 100 preterm neonates were recruited in a tertiary level neonatal intensive care unit. Inclusion criteria were gestational age ≤34 weeks or birth weight <2000 g. Biochemical markers of iron deficiency and hematological indices were serially analyzed from birth. This report focuses on the first 16 weeks after birth. Results: The trends of the studied analytes were presented with reference ranges. RBC transfusions did not have a significant effect on reticulocyte hemoglobin content (CHr) or reticulocyte count. Reticulocytes were lowest after the first week and S-TfR at 9 weeks of age. CHr and fraction of immature reticulocytes were highest at birth and decreased thereafter. CHr and reticulocyte count were significantly different in two groups determined by Hct level (Hct < or ≥0.30). This difference was not observed in S-TfR or ferritin concentrations. Conclusions: In addition to reflecting the activity of erythropoiesis, S-TfR seems to reflect iron balance in preterm neonates. By using CHr and reticulocyte, it is possible to obtain more information about iron balance in relation to erythropoiesis, and it might be useful to combine this information with Hct before making a decision about a transfusion. Clin Chem Lab Med 2008;46:551–7.

Serum trace element concentrations and iron metabolism in allogeneic bone marrow transplant recipients.

Serum trace element concentrations, parameters of iron metabolism and serum protein concentrations were investigated in thirteen adult recipients of bone-marrow transplants receiving total parenteral nutrition. Six of the patients died during the four weeks follow-up. Serum zinc concentrations were initially low but increased during the treatment. They also tended to be lower in dying patients than in survivors. Concentrations of serum copper and selenium remained unaltered. Serum iron started to increase during the preconditioning and remained raised for three weeks. No significant changes occurred in serum transferrin levels. Transferrin saturation increased during the preconditioning and started to return to normal after day +14. Serum ferritin was greatly raised from the start and increased further during the procedure. Routine trace element substitution seemed to be sufficient during total parenteral nutrition with the possible exception of zinc. A return to normal transferrin saturation after day +14 may be an early favourable sign that the graft is taking and hematopoietic recovery commencing.

Absence of Signs of Vitamin B12 ‐ Nitrous Oxide Interaction in Operating Theatre Personnel

Inactivation of vitamin B12 by nitrous oxide leads to megaloblastic haematopoiesis. Peripheral blood counts and films, serum vitamin B12 and plasma and erythrocyte folate concentrations were studied in eight anaesthetists and seven internists to find if the interaction is an occupational health hazard to operating theatre personnel chronically exposed to trace concentrations of nitrous oxide. In addition, blood counts were studied in two retrospective materials of 118 operating theatre nurses working in scavenged operating theatres and in ten subjects working in unscavenged theatres. No definite signs of B12‐nitrous oxide interaction could be observed in the peripheral blood samples from these persons.

Cell aggregation centers—initial strength elements in human wound healing☆

Abstract The cell aggregate phenomenon in human wound healing was studied by the Cellstic method in 496 surgical patients, aging from 5 to 70 years. Single cells and cell aggregates, called cell aggregation centers (CAC), were washed out of the Cellstic sponge by the retrograde injection technique 3–144 hr after surgery, centrifuged, and stained with May-Grunwald-Giemsa. A transient aggregation of the inflammatory cells on the first postoperative day was followed, from the second day on, by the persistent aggregation of polymorphonuclear leukocytes, mononuclear cells, and fibroblasts with cell-connecting intercellular substance. These turbulence resistant, gradually growing CACs are considered as early strength elements which, by fusing to each other and to the edges of the wound, essentially contribute to the increase of tensile strength in wound healing.

Increased serum soluble transferrin receptor concentration detects subclinical iron deficiency in healthy adolescent girls

Abstract The objective of this study was to investigate whether the measurement of serum soluble transferrin receptor could detect subclinical iron deficiency in adolescent girls, and to assess the possible specificity-compromising effects of growth, menarche, and intensive physical activity. The study population consisted of 191 physically active (control) girls aged 9–15 years. Dietary iron intake was estimated at baseline, and after 6 and 12 months. Iron status of the subjects was assessed by haematological laboratory tests at 6 and 12 months. A 3-month iron and multivitamin supplementation was started after the visit at 6 months. The supplementation consistently decreased soluble transferrin receptor concentrations in subjects with initial values greater than 2.4 mg/l, which was determined by regression analysis to be the cut-off value for iron-deficient erythropoiesis. The 95% reference interval in the iron-replete subjects (0.9–2.4 mg/l) was consistent with this finding. In our population, the incidence of subclinical iron deficiency was 10%. Growth or physical activity had no effect on the iron status. This study shows that, similarly to adults, soluble transferrin receptor measurement can be used to detect subclinical iron deficiency in adolescents (competitive athletes or normal controls). We suggest that soluble transferrin receptor concentrations above 2.4 mg/l indicate clinically relevant iron deficiency in adolescents.

Serum oncostatin M in multiple myeloma : association with prognostic factors

The serum concentration of oncostatin M (OSM) was measured in 40 multiple myeloma patients at diagnosis. Serum OSM level exceeded the sensitivity limit of the ELISA assay in eight (20%) of these patients (OSM+ patients). The serum levels of IL‐6, another member of the gp130 cytokine family, and C‐reactive protein (CRP) as a surrogate of IL‐6 were significantly higher in OSM+ patients. There was a trend towards higher serum β2M concentration in OSM+ patients, whereas there was no difference in the serum sIL‐6R level or clinical data (age, gender, myeloma protein or stage) between the two groups. Two human myeloma cell lines secreted OSM and IL‐6, but not IL‐11 or leukaemia inhibitory factor (LIF), which suggests an important role for OSM and IL‐6 in supporting growth of myeloma cells.

Granulocyte microbicidal function in patients undergoing major abdominal surgery under balanced anaesthesia

Granulocyte microbicidal functions were studied in 11 major abdominal surgery patients with the luminol‐enhanced chemiluminescence method. The responses of granulocytes in phagocytosis of zymosan, S. aureus and E. coli and responses to N‐formylmethionyl‐leucylphenylalanine (FMLP) were unaffected by surgery. The percentage of high‐peroxidase‐activity cells among neutrophils was increased on postoperative days 1 (P<0.01) and 3–4 (P<0.05). We propose that microbicidal‐related oxidative phagocytic functions of granulocytes are well maintained after major abdominal surgery under balanced anaesthesia.