Blood cell and iron status analytes of preterm and full-term infants from 20 weeks onwards during the first year of life.

BACKGROUND: The goal of this study was to evaluate the dynamics of blood cell and iron status laboratory analytes in preterm and full-term infants during the first year of life. METHODS: This was a prospective study of 100 preterm and 50 full-term infants. Preterm infants received iron supplementation beginning at 3 weeks of age. Laboratory tests were serially analyzed up to 12 months of corrected age. RESULTS: Estimated means and the 95% reference intervals (RIs) from 20 weeks of age and onwards are presented separately for preterm and full-term infants. At the age of 20 weeks, mean hemoglobin (Hb) in preterm infants was lower than mean Hb in full-term infants, but this difference changed during follow-up. Ferritin concentrations were initially lower in preterm infants, but decreased to similar levels in both groups. Estimated mean values for transferrin receptor and reticulocyte Hb content were quite stable between the ages of 20 and 55 weeks in both groups. CONCLUSIONS: Our study suggests that the same RIs for preterm and full-term infants can be used from the age of 20 or 30 weeks onwards, depending on the analyte. The RIs will help physicians detect iron deficiency or other problems of erythropoiesis in infants.

Simultaneous quantitative analysis of Fc gamma RI (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.

Comparison of degranulation of easily mobilizable intracellular granules by human phagocytes in healthy subjects and patients with infectious diseases.

The aim of this study was to compare degranulation of easily mobilizable secretory vesicles (SVs) or secretory vesicle-like granules (SVLGs) in neutrophils, monocytes, and eosinophils of healthy controls (n = 60) and febrile patients with microbiologically confirmed or clinically diagnosed bacterial (n = 89) and viral (n = 46) infections. For this purpose, flow cytometric immunophenotyping of isolated phagocytes was performed using monoclonal antibodies against the phagocytosis receptors CR1 (CD35) and CR3 (CD11b) that are predominantly stored in the SVs of resting neutrophils. Similar to neutrophils, monocytes contain easily mobilizable SVLGs that constitute the main intracellular reservoir of CD35 and CD11b. In both neutrophils and monocytes, activation mechanisms leading to degranulation of SV and SVLG appeared dependent on both intra- and extracellular calcium levels. The kinetics of degranulation of SVLGs in control monocytes was significantly faster than that of SVs of control neutrophils. We conclude that phagocytes in patients with bacterial infections can be arranged in order of decreasing magnitude of SV or SVLG degranulation as follows (from left to right): neutrophils > monocytes " eosinophils. However, in viral infections, the corresponding degranulation order is monocytes > neutrophils approximately eosinophils.

CRP/CD11b ratio: a novel parameter for detecting gram-positive sepsis.

To commence proper antibiotic treatment in sepsis, timely knowledge of whether the cause of systemic infection is gram-negative (gram(-)) or gram-positive (gram(+)) bacteria in origin would be beneficial for clinicians. In this clinical prospective study, our objective was to develop a method for distinguishing between gram(+) and gram(-) bacterial infection. In gram(-) bacterial infection (n = 21), the average amount of CD11b on neutrophils was significantly higher than in gram(+) bacterial infection (n = 22). On the contrary, serum C-reactive protein (CRP) level was significantly higher in gram(+) than in gram(-) bacterial infection. By dividing the serum CRP value by the amount of CD11b on neutrophils, we derived a novel marker of gram(+) sepsis, CRP/CD11b ratio, which displayed 76% sensitivity and 80% specificity for the detection of gram(+) sepsis (n = 17) among febrile patients with microbiologically confirmed or clinically diagnosed bacterial infection. The detection of gram(+) sepsis is possible after the combination of neutrophil CD11b data and serum CRP level. In conclusion, our findings indicate that the proposed CRP/CD11b ratio test could potentially assist physicians in determining an appropriate antibiotic treatment in patients with severe bacterial infection.

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

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 < or =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 > 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.

A novel method for distinguishing between dsDNA and ssRNA virus infections.

BACKGROUND: To commence proper antiviral treatment, timely knowledge of whether the infection is caused by DNA or RNA virus would be beneficial for the clinician. OBJECTIVES: Our objective was to develop a method for distinguishing between DNA and RNA virus infections. STUDY DESIGN: In this prospective study, total and differential count of leukocytes, serum C-reactive protein level, erythrocyte sedimentation rate, and quantitative flow cytometric analysis of FcgammaRI (CD64) on neutrophils and monocytes were obtained from 289 hospitalized febrile patients. After microbiological confirmation, 89 patients (31%) were found to have either bacterial (n=46) or viral (n=43) infection. The patient data was compared to 60 healthy controls. RESULTS: For the first time ever, it was noticed that in dsDNA virus infections (n=21) the average amount of CD64 on neutrophils was over five-fold compared to ssRNA virus infections (n=22). CONCLUSIONS: DNA virus score (DNAVS) point, which incorporates quantitative analysis of CD64 on neutrophils and total and differential count of leukocytes, varied between 0 and 8, and displayed 95% sensitivity and 100% specificity in distinguishing between dsDNA and ssRNA virus infections [average (S.D.); DNAVS points: 5.4 (2.5) vs. 0.3 (0.4); p<0.001].

Simultaneous quantitative analysis of FcgammaRI (CD64) expression on neutrophils and monocytes: a new, improved way to detect infections.

We performed simultaneous quantitative flow cytometric analysis of neutrophil and monocyte FcgammaRI (CD64) in 289 hospitalized febrile patients. Microbiological evaluation or clinical diagnosis confirmed bacterial (n=89) or viral (n=46) infection in 135 patients. Patient data were compared with data from 60 healthy controls. The average number of FcgammaRI on the surfaces of both neutrophils and monocytes was significantly increased in patients with febrile viral and bacterial infections, compared to healthy controls. Furthermore, we describe a novel marker of febrile infection, designated 'CD64 score point', which incorporates the quantitative analysis of FcgammaRI expressed on both neutrophils and monocytes, with 94% sensitivity and 98% specificity in distinguishing between febrile infections and healthy controls. By contrast, analysis of FcgammaRI expression on neutrophils and monocytes displayed poor sensitivity (73% and 52%) and specificity (65% and 52%) in distinguishing between bacterial and viral infections, and the levels did not differ significantly between systemic (sepsis), local, and clinically diagnosed bacterial infections. In summary, our results clearly show that the increased number of FcgammaRI on neutrophils and monocytes is a useful marker of febrile infection, but cannot be applied for differential diagnosis between bacterial and viral infections or between systemic and local bacterial infections.

Quantitative analysis of complement receptors, CR1 (CD35) and CR3 (CD11b), on neutrophils improves distinction between bacterial and viral infections in febrile patients: comparison with standard clinical laboratory data.

There is an ongoing need for sensitive and specific markers of bacterial infection. In this prospective study, standard clinical laboratory data (neutrophil count, serum C reactive protein level, erythrocyte sedimentation rate) and quantitative flow cytometric analysis of neutrophil complement receptors, CR1 and CR3, were obtained from 289 hospitalized febrile patients. After microbiological confirmation or clinical diagnosis, 135 patients were found to have either bacterial (n = 89) or viral (n = 46) infection. The patient data was compared to 60 healthy controls. In bacterial infections, all measured variables were significantly increased, particularly the average amounts of CR1 and CR3 on neutrophils were over three-fold and two-fold higher, respectively, compared to viral infections and controls. We described a novel marker of local and systemic bacterial infections designated 'clinical infection score (CIS) point', which incorporates quantitative analysis of complement receptors on neutrophils and standard clinical laboratory data. CIS point varied between 0 and 8, and displayed 98% sensitivity and 97% specificity in distinguishing between bacterial and viral infections [average (S.D.); CIS points: 6.2 (1.7) vs. 0.6 (1.0); p < 0.001]. These findings suggest that the proposed CIS-based diagnostic test could potentially assist physicians in deciding whether antibiotic treatment is necessary.

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

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.