Routine Complete Blood Cell Count Research Articles

Has COVID-19 Modified the Weight of Known Systemic Inflammation Indexes and the New Ones (MCVL and IIC) in the Assessment as Predictive Factors of Complications and Mortality in Acute Pancreatitis?

We aimed at evaluating the prognostic capacity of the inflammatory indices derived from routine complete blood cell counts in two groups of patients with acute pancreatitis from two different time periods, before and during the COVID-19 pandemic, when a high incidence of complications with surgical risk and mortality was found. Two new markers were introduced: the mean corpuscular volume to lymphocyte ratio (MCVL) and the cumulative inflammatory index (IIC), which were calculated at a baseline in the two groups of patients. Of the already established markers, none of them managed to effectively predict the complications with surgical risk and mortality, with a decrease of less than 50% in specificity in the peri-COVID group. The MCVL had the best prediction of complications with surgical risk in both the pre-COVID and peri-COVID groups, validated it as an independent factor by multivariate analysis. The IIC had the best prediction of mortality in both periods and was proven to be an independent factor by multivariate analysis. As the IIC predicted death best, we tested the occurrence of death and found that patients with PA who had an IIC > 12.12 presented a risk of death 4.08 times higher in the pre-COVID group and 3.33 times higher in the peri-COVID group. The new MCVL and IIC independent markers had a superior sensitivity and specificity in predicting surgical risk complications and, respectively, mortality in the group of patients with acute pancreatitis during the COVID-19 pandemic, which makes them widely applicable in populations with modified immune and inflammatory status. Conclusions: In patients with acute pancreatitis, MCVL has a significant predictive value regarding complications with surgical risk (abscess, necrosis, and pseudocyst), and the IIC has a significant predictive value for mortality.

Monocyte Distribution Width in Children With Systemic Inflammatory Response: Retrospective Cohort Examining Association With Early Sepsis.

To investigate the association between increased monocyte distribution width (MDW) and pediatric sepsis in the emergency department (ED). Retrospective cohort study. A single academic hospital study. Patients from birth to the age of 18 years who presented at the ED of an academic hospital with systemic inflammatory response syndrome (SIRS) were consecutively enrolled. Sepsis was diagnosed using the International Pediatric Surviving Sepsis Campaign criteria. Antibiotic treatment was administrated once infection was suspected. Routine complete blood cell count, neutrophil-to-lymphocyte ratio (NLR), and MDW, a new inflammatory biomarker, were evaluated in the ED. Logistic regression models were used to explore associations with early pediatric sepsis. We included 201 patients with sepsis and 1,050 without sepsis. In the multivariable model, MDW greater than 23 U (odds ratio [OR], 4.97; 95% CI, 3.42-7.22; p < 0.0001), NLR greater than 6 (OR, 2.06; 95% CI, 1.43-2.94; p = 0.0001), WBC greater than 11,000 cells/µL (OR, 6.52; 95% CI, 4.45-9.53; p < 0.0001), and the SIRS score (OR, 3.42; 95% CI, 2.57-4.55; p < 0.0001) were associated with pediatric sepsis. In subgroup analysis, MDW greater than 23 U remained significantly associated with sepsis for children 6-12 years old (OR, 6.76; 95% CI, 2.60-17.57; p = 0.0001) and 13-18 years (OR, 17.49; 95% CI, 7.69-39.76; p = 0.0001) with an area under the receiver operating curve of 0.8-0.9. MDW greater than 23 U at presentation is associated with the early diagnosis of sepsis in children greater than or equal to 6 years old. This parameter should be considered as a stratification variable in studies of pediatric sepsis.

Beyond the In-Practice CBC: The Research CBC Parameters-Driven Machine Learning Predictive Modeling for Early Differentiation among Leukemias.

A targeted and timely treatment can be a beneficial tool for patients with hematological emergencies (particularly acute leukemias). The key challenges in the early diagnosis of leukemias and related hematological disorders are their symptom-sharing nature and prolonged turnaround time as well as the expertise needed in reporting confirmatory tests. The present study made use of the potential morphological and immature fraction-related parameters (research items or cell population data) generated during complete blood cell count (CBC), through artificial intelligence (AI)/machine learning (ML) predictive modeling for early (at the pre-microscopic level) differentiation of various types of leukemias: acute from chronic as well as myeloid from lymphoid. The routine CBC parameters along with research CBC items from a hematology analyzer in the diagnosis of 1577 study subjects with hematological neoplasms were collected. The statistical and data visualization tools, including heat-map and principal component analysis (PCA,) helped in the evaluation of the predictive capacity of research CBC items. Next, research CBC parameter-driven artificial neural network (ANN) predictive modeling was developed to use the hidden trend (disease’s signature) by increasing the auguring accuracy of these potential morphometric parameters in differentiation of leukemias. The classical statistics for routine and research CBC parameters showed that as a whole, all study items are significantly deviated among various types of leukemias (study groups). The CPD parameter-driven heat-map gave clustering (separation) of myeloid from lymphoid leukemias, followed by the segregation (nodding) of the acute from the chronic class of that particular lineage. Furthermore, acute promyelocytic leukemia (APML) was also well individuated from other types of acute myeloid leukemia (AML). The PCA plot guided by research CBC items at notable variance vindicated the aforementioned findings of the CPD-driven heat-map. Through training of ANN predictive modeling, the CPD parameters successfully differentiate the chronic myeloid leukemia (CML), AML, APML, acute lymphoid leukemia (ALL), chronic lymphoid leukemia (CLL), and other related hematological neoplasms with AUC values of 0.937, 0.905, 0.805, 0.829, 0.870, and 0.789, respectively, at an agreeably significant (10.6%) false prediction rate. Overall practical results of using our ANN model were found quite satisfactory with values of 83.1% and 89.4.7% for training and testing datasets, respectively. We proposed that research CBC parameters could potentially be used for early differentiation of leukemias in the hematology–oncology unit. The CPD-driven ANN modeling is a novel practice that substantially strengthens the predictive potential of CPD items, allowing the clinicians to be confident about the typical trend of the “disease fingerprint” shown by these automated potential morphometric items.

Dermatologic Manifestations of Systemic Diseases in Childhood

Dermatologic Manifestations of Systemic Diseases in Childhood

Potential usefulness of complete blood count parameters and inflammatory ratios as simple biomarkers of depression and suicide risk in drug-naive, adolescents with major depressive disorder

We determined whether an elevated neutrophil-to-lymphocyte ratio (NLR), platelet–to–lymphocyte ratio (PLR), and monocyte–to–lymphocyte ratio (MLR) were associated with depression in major depressive disorder (MDD), or suicide risk in MDD patients. A total of 137 adolescents with MDD who were antidepressant-naïve and 56 healthy controls (HC) were included. Recent suicidal behaviors were assessed. The NLR, PLR, and MLR were calculated from parameters obtained from a routine complete blood cell count parameters and compared between the MDD subgroups and HC. Cohen's d was calculated as a measure of effect size. The linear relationship between biomarkers with depression severity or suicidality severity was also analysed. Changes in CBC parameters and inflammatory ratios appeared to be more closely related to the suicidality severity than depressive severity. As compared with HC, the WBC count, neutrophil percentage, platelet count, NLR, and PLR were higher in MDD, whereas the lymphocyte percentage was lower. As compared to non-suicidal ideation (non-SI) MDD and HC, the lymphocyte percentage was decreased in MDD with suicidal attempts (SA), whereas monocyte count and MLR were increased. Suicidal attempts in MDD patients were associated with the lower lymphocytes percentage, as well as the elevated monocyte count and MLR.

The Aggregate Index of Systemic Inflammation (AISI): A Novel Prognostic Biomarker in Idiopathic Pulmonary Fibrosis.

Variable patterns of disease progression are typically observed in patients with idiopathic pulmonary fibrosis (IPF). We sought to determine the prognostic capacity of blood cell count indexes, derived from routine complete blood cell (CBC) count, in a cohort of IPF patients. The neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) were calculated at baseline in a consecutive series of 82 IPF patients followed for four years. After adjusting for age, gender, body mass index, smoking status, and disease stage, only the AISI was significantly associated with mortality (HR 1.0013, 95% CI 1.0003–1.0023, p = 0.015). Patients with AISI <434 and ≥434 had a median survival from the diagnosis of 35.3 ± 15.2 and 26.6 ± 16.3 months (p = 0.015), and a four-year survival rate of 54% and 34%, respectively. The AISI, easily derivable from routine laboratory tests, is independently associated with mortality in patients with IPF. Prospective studies in larger cohorts are required to confirm this association.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Twins Compared with Singletons.

It is well known that twin pregnancies confer a high degree of adverse perinatal outcomes. Fetal growth restriction, preterm labor/delivery, and hypertensive disorders of pregnancy are among the causal etiologies associated. Hematologic parameters, specifically, the neutrophil:lymphocyte ratio (NLR), the platelet:lymphocyte ratio (PLR), and some of the routine complete blood cell count components denote a peculiar inflammatory and immunologic profile and have been used as clinical markers for specific obstetric syndromes. To our knowledge, no study has ever evaluated NLR/PLR in twins as a distinct population from singletons. Our primary objective was to analyze NLR/PLR in twins compared with singletons. Our secondary objective was to compare white blood cells, neutrophils, lymphocytes, and platelets between twins and singletons. We conducted a retrospective case-control study comparing NLR/PLR markers in twin gestations (dichorionic/diamniotic and monochorionic/dichorionic) versus singleton pregnancies, from January 2019 to April 2020. We excluded pregnancies with potential confounding factors such as human immunodeficiency virus, chronic hypertension, smoking, pregestational diabetes mellitus, or cases with miscarriage/intrauterine fetal demise. We included twin pregnancies (two fetuses) as cases and singletons as controls. We recruited 29 twins and 29 singletons, matched for age, body mass index, and parity. NLR was statistically significantly higher in the first trimester in twins compared with singletons (3.3 vs 2.7, P < 0.01) and the platelet value was lower in the second trimester in twins compared with singletons (199 vs 251, P = 0.01). We speculate that a decrease in NLR from the first to the second trimester and a decrease in platelet in the second trimester reflect both the physiologic inflammatory/immune reaction of early pregnancy and denote a vital response for the development of normal placentation in twin gestations.

Increased Systemic Immune-Inflammation Index Levels in Patients with Dry Eye Disease

ABSTRACT Purpose To evaluate the systemic immune-inflammation index (SII) levels, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in patients with dry eye disease (DED) and to compare with control subjects. Methods This prospective study included 47 DED patients and 47 age- and sex-matched healthy controls. Ophthalmological examination, diagnostic DED tests, and routine complete blood cell count parameters were analyzed. The SII value was calculated as follows: platelet count × (neutrophil/lymphocyte). Results The mean SII, NLR, and PLR levels were significantly higher in DED patients compared to controls (p < .001, p < .001 and p = .009, respectively). Using the receiver operating characteristics (ROC) curve analysis to predict patients with DED, the highest area under the curve (AUC) was determined SII (0.761 for SII, 0.727 for NLR, and 0.653 for PLR). Conclusions As a novel tool superior to other inflammatory markers, SII may be a cheap and reliable indicator of inflammatory status in DED patients.

Eosinopenia and COVID-19.

Early diagnosis of coronavirus disease 2019 (COVID-19) and patient isolation are important for both individual patient care and disease containment. The diagnosis is confirmed by testing for the presence of nasopharyngeal viral RNA with a polymerase chain reaction assay, which has limited availability, variable turnaround time, and a high false-negative rate. The authors report that a rapid laboratory test, the eosinophil count, readily obtained from a routine complete blood cell count (CBC), may provide actionable clinical information to aid in the early recognition of COVID-19 in patients, as well as provide prognostic information. To investigate the diagnostic and prognostic value of eosinopenia in COVID-19-positive patients. The eosinophil results of routine CBC from the first 50 admitted COVID-19-positive patients were compared with the eosinophil results of 50 patients with confirmed influenza infection at the time of presentation to the emergency department at Coney Island Hospital in Brooklyn, New York. The number of patients with 0 eosinophils on the day of presentation was also compared between the 2 groups. Furthermore, the eosinophil counts in the 50 COVID-19 patients were reviewed for the first 5 days of their hospital stay and before discharge, along with the outcome (deceased vs discharged), and trends in eosinophil data were compared based on the outcome. On the day of presentation, 30 patients in the COVID-19 group (60%) and 8 patients in the influenza group (16%) had an eosinophil count of 0. An additional 14 patients in the COVID-19 group had 0 eosinophils during the following 2 days; the total number of patients in the COVID-19 group who had 0 eosinophils on admission or during the ensuing 2 days was 44 (88%). In addition, 18 of 21 deceased patients in the COVID-19 group (86%) who initially presented with eosinopenia remained eosinopenic compared with 13 of 26 survivors (50%). The absence of an eosinophil count in a CBC can aid in early diagnosis of COVID-19. It may be a useful tool in deciding whether to promptly isolate a patient and initiate specific therapies while waiting for confirmatory test results. Persistent eosinopenia after admission correlated with high disease severity and low rates of recovery.

Association between gestational age at delivery and lymphocyte-monocyte ratio in the routine second trimester complete blood cell count.

BackgroundWe aimed to determine whether routine second trimester complete blood cell (CBC) count parameters, including neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), and platelet-lymphocyte ratio (PLR), could predict obstetric outcomes.MethodsWe included singleton pregnancies for which the 50-g oral glucose tolerance test and CBC were routinely performed between 24 and 28 weeks of gestation in our outpatient clinic from January 2015 to December 2017. The subjects were divided into three groups according to their pregnancy outcomes as follows: group 1, spontaneous preterm births, including preterm labor and preterm premature rupture of membranes; group 2, indicated preterm birth due to maternal, fetal, or placental causes (hypertensive disorder, fetal growth restriction, or placental abruption); and group 3, term deliveries, regardless of the indication of delivery. We compared the CBC parameters using a bivariate correlation test.ResultsThe study included 356 pregnancies. Twenty-eight subjects were in group 1, 20 in group 2, and 308 in group 3. There were no significant differences between the three groups in neutrophil, monocyte, lymphocyte, and platelet counts. Although there was no significant difference in NLR, LMR, and PLR between the three groups, LMR showed a negative correlation with gestational age at delivery (r=−0.126, p=0.016).ConclusionWe found that a higher LMR in the second trimester was associated with decreased gestational age at delivery. CBC parameters in the second trimester of pregnancy could be used to predict adverse obstetric outcomes.

An elevated neutrophil-to-lymphocyte ratio associates with weight loss and cachexia in cancer

Systemic inflammation is present during and serves as a diagnostic tool for cancer-associated cachexia and is detrimental to serum 25-hydroxyvitamin D (25(OH)D) concentrations in non-cancer conditions. The neutrophil-to-lymphocyte ratio (NLR) is a desirable measure of systemic inflammation because it is easily calculated from a routine complete blood cell count with differentials. We sought to determine if an elevation in the NLR associates with greater weight loss, cachexia, and lower serum 25-hydroxyvitamin D (25(OH)D) concentrations in patients with advanced cancer. Advanced colon, lung, and prostate cancer patients (stages III/IV; n = 50) were retrospectively studied and separated into one of two groups: 1) Above (n = 25) or 2) Below (n = 25) the median NLR of 3.15 determined at diagnosis. Around the time of diagnosis, serum 25(OH)D and body weight were assessed, while body weight was assessed again at a later date. Weight loss and cachexia were significantly (both p < 0.05) greater and there was a trend (p < 0.10) for lower serum 25(OH)D concentrations in the Above group. We conclude that an elevation in the NLR associates with greater weight loss and cachexia, and potentially, a lower serum 25(OH)D concentration in patients with advanced colon, lung, or prostate cancer.

Age-related prevalence and clinical significance of neutropenia - isolated or combined with other cytopenias: Real world data from 373 820 primary care individuals.

Neutropenia (NP), that is, an absolute blood neutrophil count (ANC) <1.5 g/L, accompanies various diseases. However, the clinical significance of NP, detected in routine complete blood cell counts (CBC) in primary care, is poorly characterized. Here, from a primary care resource with ANCs from >370 000 individuals, we identified and followed neutropenic subjects for the next 4 years for novel ICD-10 based diagnoses of viral infections and hematological malignancies (ie, previously identified major outcomes in NP individuals) in Danish nationwide health registers. Risk estimates were assessed for children/adolescents (1-18 years) and adults (19-90 years) in relation to NP severity, and for isolated NP, bi- or pancytopenias. We found that NP was observed in 4.9% of children and in 1.9% of adults. The lower the ANC, the likelier was a diagnosis of viral infections or hematological malignancies established during the ensuing 4 years. Among neutropenic children, unspecified viral infections predominated, followed by mononucleosis (with other cytopenias in only 7% and 25% of the cases, respectively). All NP children with acute leukemia presented with bi- or pancytopenia from start of follow-up. In NP adults, hepatitis, followed by HIV, were the most common infections, and acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDSs) the predominating hematological malignancies. Adult NP patients, subsequently diagnosed with hepatitis, HIV or AML, MDS, were bi- or pancytopenic in 42%, 47%, 90% and 91% of cases, respectively. Thus, presence of NP in even one CBC may be the first sign of a latent viral or hematological disorder requiring careful follow-up.

P.2.d.013 - Association between inflammation, oxidative stress and clinical features of bipolar disorder manic episode

We determined whether an elevated neutrophil-to-lymphocyte ratio (NLR), platelet–to–lymphocyte ratio (PLR), and monocyte–to–lymphocyte ratio (MLR) were associated with depression in major depressive disorder (MDD), or suicide risk in MDD patients. A total of 137 adolescents with MDD who were antidepressant-naïve and 56 healthy controls (HC) were included. Recent suicidal behaviors were assessed. The NLR, PLR, and MLR were calculated from parameters obtained from a routine complete blood cell count parameters and compared between the MDD subgroups and HC. Cohen's d was calculated as a measure of effect size. The linear relationship between biomarkers with depression severity or suicidality severity was also analysed. Changes in CBC parameters and inflammatory ratios appeared to be more closely related to the suicidality severity than depressive severity. As compared with HC, the WBC count, neutrophil percentage, platelet count, NLR, and PLR were higher in MDD, whereas the lymphocyte percentage was lower. As compared to non-suicidal ideation (non-SI) MDD and HC, the lymphocyte percentage was decreased in MDD with suicidal attempts (SA), whereas monocyte count and MLR were increased. Suicidal attempts in MDD patients were associated with the lower lymphocytes percentage, as well as the elevated monocyte count and MLR.

Standardized laboratory monitoring with use of isotretinoin in acne

Laboratory monitoring for adverse effects to isotretinoin occurs with variability. Standardization of laboratory monitoring practices represents an opportunity to improve quality of care. We sought to develop an evidence-based approach to laboratory monitoring of patients receiving isotretinoin therapy for acne. We reviewed laboratory data from 515 patients with acne undergoing 574 courses of isotretinoin from March 2003 to July 2011. Frequency, timing, and severity of abnormalities were determined. Clinically insignificant leukopenia or thrombocytopenia occurred in 1.4% and 0.9% of patients, respectively. Elevated liver transaminases were detected infrequently and not significantly increased compared with baseline detection rates (1.9% vs 1.6% at baseline). Significant elevations occurred with triglyceride (19.3%) and cholesterol (22.8%) levels. The most severe abnormalities were grade 2 (moderate). Mean duration of treatment before abnormalities were detected was 56.3days for hypertriglyceridemia, 61.9days for alanine transaminitis, and 50.1days for hypercholesterolemia. This was a single-center experience examining variable isotretinoin laboratory monitoring practices. In healthy patients with normal baseline lipid panel and liver function test results, repeated studies should be performed after 2months of isotretinoin therapy. If findings are normal, no further testing may be required. Routine complete blood cell count monitoring is not recommended.

Prevalence and clinical significance of neutropenia discovered in routine complete blood cell counts: a longitudinal study.

Neutropenia, defined as an absolute blood neutrophil count (ANC) <1.5 G L(-1) , may accompany a variety of diseases. However, the clinical significance of neutropenia detected in a routine complete blood cell count is poorly understood. Using a primary care resource, comprising more than 370 000 individuals, we assessed the association with a number of previously recognized conditions as well as all-cause mortality in the 4 years following the identification of neutropenia. By matching laboratory data with Danish nationwide health registers, risk estimates were assessed. Neutropenia was observed in approximately 1% of all individuals and was associated dose dependently with viral infections, haematological malignancies (but not autoimmune disorders or solid cancers) and mortality. Neutropenia was particularly associated with HIV, acute leukaemias and myelodysplastic syndromes. Odds ratios [95% confidence interval (CI)] for viral infections were 2.32 (1.84-2.91), 2.80 (2.20-3.57) and 4.77 (3.22-7.07) for subnormal (≥1.5-1.8 G L(-1) ), mild (≥1.0-1.5 G L(-1) ) and moderate-severe (≥0.0-1.0 G L(-1) ) neutropenic individuals, respectively (all P < 0.001). Likewise, odds ratios (95% CI) for haematological malignancies were 3.23 (2.35-4.45), 8.69 (6.58-11.47) and 46.03 (33.98-62.35 ), for the same neutropenia levels, respectively (all P < 0.001). Thus, the lower the ANC, the greater the likelihood of these diseases. The relative risk estimates observed for severe neutropenia corresponded to absolute risks of haematological malignancies and mortality from any cause of 40% and >50%, respectively. Neutropenia is an ominous sign necessitating careful follow-up. The risk estimates presented here support focusing attention to viral diseases and haematological malignancies when neutropenia is observed.

Brak wpływu stopnia zwężenia zastawki aortalnej na standardowe parametry płytek krwi — kluczowa rola innych czynników ryzyka sercowo-naczyniowego

Introduction. Calcification of the aortic valve, the main component of degenerative aortic stenosis (AS), results in turbulent blood flow, higher shear stress and may have an effect on the platelet (PLT) parameters. Platelet function and size, which are easily measured automatically during a complete blood count, are proposed as markers of platelet reactivity and risk factors for cardiovascular diseases. Material and methods. 143 patients with AS (mean age: 70 ± 13 y., males 76/53%) were enrolled into the study and divided according to the AS severity: severe AS (n = 89; males 43/48.3%; age IQR: 70 [63–75] y.) and non-severe AS (n = 54; males 63/61.1%; age IQR: 70 [62–76] y.). The clinical data were collected and analyzed with special attention being paid to the cardiovascular risk factors, concomitant diseases (coronary artery disease [CAD], diabetes mellitus, arterial hypertension, obesity). Laboratory tests and echocardiography were assessed in all subjects. Routine admission complete blood cell count was obtained — PLT count, mean PLT volume (MPV), PLT distribution width (PDW) and percentage of giant PLT (giant PLT%) were analyzed. Results. There were no differences between the PLT count, MPV, PDW and giant PLT% when comparing the group with severe AS to the non-severe AS group. Multivariate analysis showed a significant effect of CAD coincidence (β = –0.2, SE = 0.09, p = 0,03) and active smoking (β = –0.2, SE = 0.09, p = 0.03) on the PLT count; obesity (β = 0.2, SE = 0.09, p = 0.03) and CAD (β = –0.2, SE = 0.09, p = 0.03) on MPV; obesity (β = 0.21, SE = 0.09, p = 0.02), thienopyridines (β = 0.19, SE = 0.09, p = 0.03) and LMWH intake (β = 0.21, SE = 0.09, p = 0.02) on PDW; and similarly, obesity (β = 0.23, SE = 0.09, p = 0.01), thienopyridines (β = 0.18, SE = 0.09, p = 0.046) and LMWH intake (β = 0.23, SE = 0.09, p = 0.01) on giant PLT%. Conclusions. Aortic stenosis severity has no effect on PLT count and morphology that are automatically measured. The coincidence of standard cardiovascular risk factors and the CAD effects on the PLT parameters that are established during a standard complete blood count.

Methemoglobinemia In Rhesus Monkeys Due To M-Hemoglobinopathy

M-hemoglobinopathies in humans are usually due to amino acid changes, which tend to stabilize the heme iron in ferric state and inaccessible to methemoglobin reductase. Consequently, blood methemoglobin concentrations are elevated despite normal methemoglobin reductase activity. No naturally-occurring animal models for M-hemoglobinopathies have been described. In contrast to humans where thousands of hereditary disorders and genetic predispositions to disease have been described, inborn errors of metabolism in non-human primates have been very rarely documented (e.g. globoid cell leukodystrophy). As part of an NIH-supported National Referral Center for Animal Models of Human Genetic Disease, which focuses on homologous hereditary diseases in dogs and cats, we present here the discovery and characterization of an M-hemogobinopathy in rhesus monkeys (Macaca mulatta). Adult rhesus monkeys of Chinese origin with persistent cyanotic mucous membranes and healthy controls were studied from two institutions. Despite the apparent cyanosis, these primates did clinically not show any other overt signs. Routine complete blood cell counts, chemistry screens and urinalyses as well as cardiopulmonary examinations did not reveal any abnormalities. Fresh EDTA blood samples were analyzed to determine the degree and cause of methemoglobinemia and results were compared to healthy rhesus monkeys from the same institutions. Blood methemoglobin concentrations were persistently increased to 15-30% in affected monkeys, while control animals had &lt;1% methemoglobin levels. Methemoglobin (cytochrome b5) reductase activities in erythrocytes were repeatedly measured in vitro and found to be normal compared to controls. Based upon the hemoglobin-oxygen dissociation curves and p50 values (14.8 mmHg; compared to 14.5 and 14.6 mmHg for controls) the oxygen transport function was normal. Both cation-exchange as well as reversed-phase and high performance liquid chromatography analyses revealed normal elution patterns of hemoglobin isotype and globin chains. DNA studies identified a disease-associated polymorphism in the alpha globin gene (CAC → CAA) in the affected animals. This change in the alpha globin protein was confirmed by mass spectrometry (α78 His → Gln). Our findings indicate an electrophoretically silent α-globin polymorphism is associated with methemoglobinemia in these rhesus monkeys. This is the first description of methemoglobinemia in a non-human primate and represents the first animal model of an M-hemoglobinopathy. While clinical signs were relatively mild in these rhesus monkeys, our findings represent one of the first inborn errors of metabolism described in non-human primates, thus emphasizing how unusual disorders caused by “experiments of nature” provide rare opportunities to gain a better understanding of both medicine and biology. Rhesus monkeys represent unique, valuable animal models for developing and testing new treatment options for hemoglobinopathies. Disclosures: No relevant conflicts of interest to declare.

Late-onset neutropenia: defining limits of neutrophil count in very low birth weight infants

To evaluate the incidence, onset, duration, characteristics and importance of late-onset neutropenia (defined as absolute neutrophil count<1500 μl(-1) at 3 weeks of age or later) in a group of very low birth weight (VLBW) infants. Routine complete blood cell counts (CBCs) obtained from VLBW infants over a period of 7 years were gathered retrospectively, including those of newborns with weekly CBCs taken over a duration of at least 3 weeks. Data were obtained from between January 2003 and December 2009. CBCs of 399 newborns were included. Values were obtained from birth to 36 weeks of postnatal age. Late-onset neutropenia was observed in 259 cases (65%). Neutropenic infants had a mean of 0.5 weeks lower gestational age. Late-onset neutropenia was more frequent in children with intraventricular hemorrhage but not in patients who received erythropoietin. The median age of neutropenia onset was 7 weeks in extremely low birth weight infants and 6 weeks in VLBW infants. The fifth percentile of neutrophils between weeks 3 and 4 was 1280 μl(-1) and between weeks 13 and 15 was 500 μl(-1). The average duration was 2 weeks with normalized values after 18 weeks. A neutrophil count <1500 μl(-1) after the third week of life is frequently observed in VLBW infants and should not be used as a lower reference limit. The fifth percentile varies according to postnatal age from around 1300 μl(-1) in week 4 of life, decreasing to a nadir of 500 μl(-1) between 3 and 4 months of age. Values normalize in the first year of life.

The effect of pneumatic tube system on complete blood count parameters and thrombocyte donation in healthy donors

This paper is the first report whether or not pneumatic tube system affects the selection of apheresis donors according to the results of complete blood count. According to the apheresis guidelines, hemoglobin level must be ⩾12.5g/dL and platelet level ⩾150/μL to be a donor. Paired blood samples of 26 healthy volunteers were transported by either hand delivered or a pneumatic tube system to the laboratory. No statistically significant differences were observed in order to mean values of routine complete blood cell count and white cell differential parameters that were send for selection of apheresis donor before the procedure. Therefore, all healthy volunteers decided as a donor according to the laboratory results independent from transport method.

Chronic Diarrhea in Children

Chronic Diarrhea in Children