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Genetic influences on peripheral blood cell counts: a study in baboons.

Interperson differences in peripheral blood cell counts in healthy individuals result from genetic and environmental influences. We used multivariate genetic analyses to assess the relative impact of genes and environment on baseline blood cell counts and indices using a pedigreed colony of baboons, an animal with well-documented analogies to human blood physiology. After accounting for age, sex, and weight, we found that genetic influences explain a significant proportion of the remaining variability, ranging from a low of 13.7% for mean corpuscular hemoglobin concentration (MCHC) to a high of 72.4% for red blood cell (RBC) number. Genes influence 38.5% of the variation in baseline white blood cell (WBC) count, a characteristic that correlates with mortality in both the general human population and clinically defined subgroups such as individuals with sickle-cell disease. We examined the interaction between pairs of traits and identified those that share common genetic influences (pleiotropy). We unexpectedly observed that the same gene or group of genes influences both WBC count and mean platelet volume (MPV). We anticipate that this approach will ultimately lead to discovery of novel insights into the biology of related traits, and ultimately identify important genes that affect hematopoiesis.

Animals↗

Neonatal nucleated red blood cell counts in small-for-gestational age fetuses with abnormal umbilical artery Doppler studies.

OBJECTIVE: The presence of elevated nucleated red blood cell counts in neonatal blood has been associated with fetal hypoxia. We sought to determine whether small-for-gestational-age fetuses with abnormal umbilical artery Doppler velocity waveforms have elevated nucleated red blood cell counts. STUDY DESIGN: Hospital charts of neonates with the discharge diagnosis of small for gestational age (birth weight < 10th percentile) who were delivered between October 1988 and June 1995 were reviewed for antepartum testing, delivery conditions, and neonatal outcome. We studied fetuses who had an umbilical artery systolic/diastolic ratio within 3 days of delivery and a complete blood cell count on the first day of life. Multiple gestations, anomalous fetuses, and infants of diabetic mothers were excluded. Statistical analysis included the Student t test, chi 2 analysis, analysis of variance, and simple and stepwise regression. RESULTS: Fifty-two infants met the inclusion criteria. Those with absent or reversed end-diastolic velocity (n = 19) had significantly greater nucleated red blood cell counts than did those with end-diastolic velocity present (n = 33) (nucleated red blood cells/100 nucleated cells +/- SD: 135.5 +/- 138 vs 17.4 +/- 23.7, p < 0.0001). These infants exhibited significantly longer time intervals for clearance of nucleated red blood cells from their circulation (p < 0.0001). They also had lower birth weights (p < 0.05), lower initial platelet count (p = 0.0006), lower arterial cord blood pH (p < 0.05), higher cord blood base deficit (p < 0.05), and an increased likelihood of cesarean section for "fetal distress" (p < 0.05). Multivariate analysis demonstrated that absent or reversed end-diastolic velocity (p < 0.0001) and low birth weight (p < 0.0001) contributed to the elevation of the nucleated red blood cell count, whereas gestational age at delivery was not a significant contributor. CONCLUSION: We observed significantly greater nucleated red blood cell counts and lower platelet counts in small-for-gestational-age fetuses with abnormal umbilical artery Doppler studies. This may suggest that antenatal thrombotic events lead to an increased placental impedance. Fetal response to this chronic condition may result in an increased nucleated red blood cell count.

Adult↗

White blood cell counts and malaria.

White blood cells (WBCs) were counted in 4697 individuals who presented to outpatient malaria clinics in Maesod, Tak Province, Thailand, and Iquitos, Peru, between 28 May and 28 August 1998 and between 17 May and 9 July 1999. At each site and in each year, WBC counts in the Plasmodium falciparum-infected patients were lower than those in the Plasmodium vivax-infected patients, which, in turn, were lower than those in the uninfected patients. In Thailand, one-sixth of the P. falciparum-infected patients had WBC counts of <4000 cells/microL. Leukopenia may confound population studies that estimate parasite densities on the basis of an assumed WBC count of 8000 cells/microL. For instance, in the present study, use of this conventional approach would have overestimated average asexual parasite densities in the P. falciparum-infected patients in Thailand by nearly one-third.

Adolescent↗

White blood cell count and adherence in sportsmen and non-training subjects.

The white blood cell count and differential white blood cell count as well as the adherence of these cells were determined in 31 young clinically healthy men not participating actively in any sports and in 32 footballers belonging to third league sports clubs. In the group of footballers the determinations were carried out twice: in the initial period and then at the end of the highest-form period of the one-year training cycle. In the footballers in relation to the control group the total white blood cell count was raised, the differential count showed a shift in favour of neutrophils, eosinophils and monocytes at the expense of lymphocytes. The lymphocyte adherence was significantly decreased.

Adolescent↗

Quality specification in haematology: the automated blood cell count.

BACKGROUND: Quality specifications for automated blood cell counts include topics that go beyond the traditional analytic stage (imprecision, inaccuracy, quality control) and extend to pre- and post-analytic phases. METHODS: In this review pre-analytic aspects concerning the choice of anticoagulants, maximum conservation times and differences between storage at room temperature or at 4 degrees C are considered. For the analytic phase, goals for imprecision and bias obtained with various approaches (ratio to biologic variation, state of the art, specific clinical situations) are evaluated. For the post-analytic phase, medical review criteria (algorithm, decision limit and delta check) and the structure of the report (general part and comments), which constitutes the formal act through which a laboratory communicates with clinicians, are considered. RESULTS: K2EDTA is considered the anticoagulant of choice for automated cell counts. Regarding storage, specimens should be analyzed as soon as possible. Storage at 4 degrees C may stabilize specimens from 24 to 72 h when complete blood count (CBC) and differential leucocyte count (DLC) is performed. For precision, analytical goals based on the state of the art are acceptable while for bias this is satisfactory only for some parameters. CONCLUSIONS: In haematology quality specifications for pre- and analytical phases are important, but the review criteria and the quality of the report play a central role in assuring a definite clinical value.

Automation↗

Automated haematology: construction of univariate reference ranges for blood cell count and size.

The theory of reference ranges advocated by the International Committee for Standardization in Haematology (ICSH) was tested experimentally for an aperture impedance and a flow cytometric system. The reference sample was drawn from volunteer blood donors and the sampling procedure carefully standardised. Subjects were partitioned for gender and smoking habits, and their ages noted. Reference ranges were constructed from Gaussian statistics, after objective evaluation of the data, based on an assumed occurrence of one false positive measurement in every twenty samples. Different reference ranges were obtained on the two different systems for some haematological parameters, and partitioning also produced differences in calculated reference ranges. We conclude that strict adherence to the ICSH recommendations is almost impossible. Nevertheless, it is important that all laboratories should construct their own local reference ranges for their specific analytical systems before cost effective clinical decisions can be made.

Adult↗

Blood cells and their role in regeneration. II. Effects of putative immunological manipulations on circulating blood cell counts during regeneration.

The participation of leukocytes in regeneration was studied by determining changes in circulating leukocyte counts following putative immunological manipulations. Splenectomy failed to produce leukopenia during regeneration, although a 24-35% reduction in leukocytes occurred in otherwise intact newts. Bovine serum albumin and anti-lymphocyte serum produced initial lympho- and granulocytopenias, but blood counts soon returned to more normal levels. Lymphocytosis followed treatment with cobra venom factor, but marked lymphopenia occurred shortly thereafter. Regeneration occurred in all cases. These data failed to establish a clear correlation between the nature of quantitative changes in circulating leukocyte levels following these treatments and regenerative capacity.

Animals↗

Neonatal nucleated red blood cell counts: relationship to abnormal fetoplacental circulation detected by Doppler studies.

Increased neonatal nucleated red blood cell counts are thought to be related to intrauterine hypoxemia. We sought to determine the effect of increasing circulatory impairment in fetuses on the neonatal nucleated red blood cell count. One hundred thirty-four singleton pregnancies were included in the study and were allocated to 4 study groups according to Doppler findings. The systolic-to-diastolic ratios of the umbilical artery, fetal aorta, middle cerebral artery, and uterine arteries were recorded. Fetuses were assigned to the following groups on the basis of the last Doppler examination before delivery: group 1, normal systolic-to-diastolic ratios in the examined vessels; group 2, a systolic-to-diastolic ratio greater than 2 SD above the mean for gestational age in the umbilical artery or fetal aorta and no abnormal Doppler findings in the uterine arteries; group 3, systolic-to-diastolic ratios greater than 2 SD above the mean for gestational age in all examined vessels; and group 4, absence of end-diastolic velocity in the umbilical artery or fetal aorta and systolic-to-diastolic ratios greater than 2 SD above the mean for gestational age in the uterine arteries. A blood sample from the umbilical artery was obtained within 1 minute after birth, and nucleated red blood cells per 100 white blood cells were counted by light microscopy. Nucleated red blood cell counts were higher in fetuses in group 4 (median, 72.0; range, 9-720; P < .001) and group 3 (median, 38.4; range, 7-201; P < .001) than in fetuses in group 1 (median, 5.1; range, 0-20). Neonates in group 4 had significantly lower birth weights (P < .001), lower arterial and venous pH values (P < .05), and lower Apgar scores after 5 minutes (P < .01) as well as an increased likelihood of cesarean delivery because of fetal distress (P < .001). The number of fetuses in group 4 with a cord blood base deficit of less than -8 mmol/L was increased. Nucleated red blood cell counts were comparable in fetuses in group 2 (median, 5.4; range, 0-37) and group 1. In groups 1 to 3 no brain-sparing effect occurred, whereas in 15 of 21 cases in group 4 a brain-sparing effect was present. Multivariate analysis revealed that Doppler results of the umbilical artery, fetal aorta, and uterine arteries were independent determinants of neonatal nucleated red blood cell count. Increasing abnormalities seen on fetoplacental Doppler studies are associated with increasing numbers of nucleated red blood cells at birth. Given the known relationship between abnormal Doppler flow and intrauterine hypoxemia, the neonatal nucleated red blood cell count might become an additional valuable tool in the surveillance of growth-restricted fetuses.

Aorta↗

Do blood cell counts have an independent prognostic value in primary lung cancer?

A review of the biomedical literature suggests that lymphocyte and neutrophil counts are probably the only blood cell count parameters whose independent pre-therapeutic prognostic values are significantly documented in lung cancer (and only in non small cell lung cancer). The independent pre-therapeutic prognostic value of these two parameters remains quite controversial however, and further studies should be conducted, and in particular, comparisons between neutrophils, lymphocytes, and serum cyfra 21-1. For the therapeutic follow-up, further prognostic evaluation studies are also necessary for blood cell count parameters as well as for serum cyfra 21-1. Clinical biologists still have to convince clinicians and/or journal editors that it is not scientifically acceptable for publications to omit detailing the analytical and pre-analytical methodologies used for blood cell count measurements.

Blood Cell Count↗

Umbilical vein white blood cell count as a marker of acidemia in term neonates.

OBJECTIVE: White blood cells are mobilized under both hypoxic and infectious conditions. Intrauterine hypoxia is linked to increased risk of cerebral palsy and is potentiated by the presence of infection. We hypothesized that umbilical vein white blood cell elevation in term neonates is associated with intrauterine acidemia. METHODS: We prospectively evaluated all liveborn neonates delivered at our institution for a 6-month period. Umbilical arterial blood was analyzed for pH and blood gas and venous blood for hematologic indices. Medical records of cases greater than or equal to 37 weeks' gestation were reviewed for correlative data. Student's t-test was used to determine difference of means and Chi-square test for goodness of fit. Pearson coefficients of correlation were applied where appropriate. RESULTS: A total of 1,948 liveborn, term neonates were delivered during the study period; 1,561 cases had white blood cell analysis and arterial blood gas data available. Acidemic cases had higher white blood cell (15.0 vs. 12.4 cells x 10(3)/mm3, P < 0.001), lymphocyte (4.43 vs. 3.59 cells X 10(3)/mm3, P < 0.0001), and neutrophil counts (9.08 vs. 7.71 cells x 10(3)/mm3, P < 0.01). As umbilical artery pH decreased, white blood cells became more prevalent. Likewise, as base deficit deepened, white blood cell counts increased. CONCLUSIONS: This study demonstrates an association between deepening acidemia and increasing white blood cell, lymphocyte, and neutrophil counts. Although statistically different, mean white blood cell counts for acidemic and nonacidemic cases are fairly close, limiting the clinical applicability in determining whether pathology is present in an individual case.

Acidosis↗

White blood cell count and differential count.

Current methods for performing the white blood cell count and differential count along with recent technologic advances are discussed. Sources of error and variation in these tests are presented. The use of the white blood cell count and the differential count in a variety clinical situations is reviewed.

Adolescent↗

Effects of time, temperature and blood cell counts on levels of lactate in heparinized whole blood gas samples.

OBJECTIVE: To investigate whether lactate levels may vary in relation to time, substrate concentration and blood cells counts. METHODS: In this study 110 samples from the daily clinical routine blood samples were collected. Determinations of lactate were made at different times where the samples had not been left for more than 120 min at room temperature (24 degrees C) or in the fridge (4 degrees C). The influence of glucose and blood cells on lactate production was also estimated. The rate in change of concentration (slope) and the increase expected at the beginning (intercept) were estimated through linear regression using a longitudinal marginal method. RESULTS: The time-related change in lactate was significantly higher at room temperature (0.012 mmol L(-1) min(-1)) than at 4 degrees C (0.0035 mmol L(-1) min(-1)) (p<0.0001). There was a significantly positive relationship between blood cells (mainly leucocytes) and the rate of reaction at room temperature. CONCLUSIONS: A delay in the processing of a whole blood sample of more than 15 min at room temperature or an hour in the fridge entails an important overestimation of the initial lactate levels. Pronounced leucocytosis (higher than 6 x 10(10)/L) meaningfully cut down the stability period (10 min).

Blood Cell Count↗

Significance of high and normal neonatal nucleated red blood cell count in small-for-gestational-age newborns.

The objective of this study was to evaluate the obstetrical and neonatal outcome in small-for-gestational age (SGA) and appropriate-for-gestational-age (AGA) fetuses with normal and elevated neonatal nucleated red blood cell counts. Therefore the nucleated red blood cell count was assessed immediately after birth in 906 neonates delivered at our institution and the perinatal and neonatal data were compared. Postnatally, infants were classified as SGA if they had a birth weight for given gestational age below the 10th percentile. Neonates were allocated to four groups according to their nucleated red blood cell count: SGA neonates with normal and high nucleated red blood cell count and appropriate-for-gestational-age newborns (AGA) with normal and high nucleated red blood cell count. Statistical analysis included the Mann-Whitney U-Test, Student's t-test, chi2 analysis of variance and stepwise regression analysis. SGA newborns with high nucleated red blood cell count had a significantly lower birth weight, a lower gestational age at delivery, lower arterial and venous pH values, lower Apgar scores at 1 min, 5 min and 10 min as well as lower base excess values compared to the other groups. They had to be transferred significantly more often and stayed longer in the neonatal intensive care unit. Three cases of intraventricular hemorrhage, four cases of necrotizing enterocolotis and two neonatal deaths occurred all in the SGA group with high neonatal nucleated red blood cell counts. Neonatal outcomes of SGA and AGA newborns with normal nucleated red blood cell counts were comparable. Our data do therefore underline the possible value of neonatal nucleated red blood cell counts to differentiate the healthy small-for-gestational age newborn from the truely growth retarded newborn.

Apgar Score↗

Nucleated red blood cell count in the differentiation of fetuses with pathologic growth restriction from healthy small-for-gestational-age fetuses.

OBJECTIVE: The purpose of this study was to evaluate the utility of the neonatal nucleated red blood cell count in differentiating the fetus with growth restriction from the small but otherwise healthy fetus. STUDY DESIGN: Perinatal outcomes were evaluated prospectively for all neonates admitted to the neonatal intensive care unit in 1997. Nonanomalous neonates with normal phenotype and a complete blood cell count performed within the first 6 hours after birth were included in the study. All neonates with birth weights lower than the 10th percentile for gestational age were considered small for gestational age. Neonates were divided into four groups: small-for-gestational-age neonates with elevated nucleated red blood cell counts, appropriately grown neonates with elevated nucleated red blood cell counts, small-for-gestational-age neonates with normal nucleated red blood cell counts, and appropriately grown neonates with normal nucleated red blood cell counts. Analysis of variance, chi(2) tests, and stepwise regression were used for statistical analysis. RESULTS: Two hundred thirty-seven neonates met the inclusion criteria. Forty-three were small for gestational age. Small-for-gestational-age neonates with high nucleated red blood cell counts had significantly lower umbilical artery pH and were more likely to require mechanical ventilation or blood pressure support agents. Subgroup analysis demonstrated that small-for-gestational-age neonates with elevated nucleated red blood cell counts had significantly more adverse outcomes than did small-for-gestational-age neonates with normal nucleated red blood cell counts. Outcomes of small-for-gestational-age neonates with normal nucleated red blood cell counts were essentially identical to those of appropriately grown neonates. CONCLUSION: An elevated nucleated red blood cell count may distinguish the fetus with growth restriction from the small but healthy fetus.

Erythroblasts↗

The relationship of white blood cell count to other cardiovascular risk factors.

Baseline data for the 12,866 men from the Multiple Risk Factor Intervention Trial was used to study factors related to white blood cell (WBC) count. White blood cell count was significantly higher in smokers (7853 cells/mm3) and ex-smokers (7091 cells/mm3) who stopped smoking less than one year before than in ex-smokers who stopped more than one year before (6255 cells/mm3) and those who never smoked (6094 cells/mm3). In current cigarette smokers, white blood cell count was significantly related to number of cigarettes smoked, degree of inhalation, and duration of smoking (p less than 0.001 for each). In addition, white blood cell count was higher in non-cigarette smokers who smoked pipes, cigars, or cigarillos than among men who did not smoke tobacco (p less than 0.001). White blood cell count was lower in blacks (by 877 cells/mm3) and Orientals (by 634 cells/mm3) than in whites. Leukocyte count also showed a strong inverse association with high density lipoprotein (HDL)-cholesterol, a positive association with triglycerides independent of cigarette use, and a positive association with low density lipoprotein (LDL)-cholesterol in smokers only. Leukocyte counts were inversely related to total family income and alcohol consumption. We conclude that elevated leukocyte count is independently associated with other risk factors for coronary heart disease (CHD) such as amount and duration of smoking as well as an atherogenic profile, and these relationships should be considered when using white blood cell count as a predictor of coronary heart disease.

Adult↗

Nucleated red blood cell count at birth as an index of perinatal brain damage.

OBJECTIVE: The prognostic value of the nucleated red blood cell count at birth with respect to perinatal brain damage and neonatal outcome was assessed in infants at high risk of having neurologic damage. STUDY DESIGN: The nucleated red blood cell count at birth, pulsed Doppler ultrasonography in the cerebral arteries, cranial fontanelle sonograms, and neurodevelopmental status were evaluated in 337 newborn infants. RESULTS: The nucleated red blood cell count at birth was significantly higher (1) in neonates with abnormal Doppler ultrasonographic parameters for the cerebral arteries at 48 to 72 hours after birth than in healthy neonates, (2) in 6-month-old infants with sequelae of hypoxic-ischemic encephalopathy than in healthy infants, and (3) in 3-year-old children with abnormal developmental status than in those with no abnormalities at follow-up. Significant correlations were observed between the nucleated red blood cell count and gestational age, Apgar score at 1 and 5 minutes, pH, base deficit, fraction of inspired oxygen, blood oxygen content, and birth weight. CONCLUSIONS: The nucleated red blood cell count at birth not only reflects a response of the infant to perinatal hypoxia but is also a reliable index of perinatal brain damage.

Apgar Score↗