Role Of White Blood Cells Research Articles

Genetic variants associated with white blood cell count amongst individuals with sickle cell disease.

Sickle cell disease (SCD) is a Mendelian disorder characterized by a point mutation in the β-globin gene that leads to sickling of erythrocytes. Several studies have shown that absolute neutrophil count is strongly associated with clinical severity of SCD, suggesting an apparent role of white blood cells (WBC) in SCD pathology. However, the mechanism by which genetic variants lead to WBC count differences in SCD patients remains unclear. Genome-wide association (GWA) analyses were carried out amongst a cohort of 2409 Brazil SCD participants. Association of WBC count and genetic markers were investigated in homozygous sickle cell anaemia participants and compound heterozygous sickle cell haemoglobin C participants. GWA analysis showed that variants in genes TERT, ACKR1, and FAM3C are associated with WBC count variation. The well-studied association between WBC count and Duffy null phenotype (variant in ACKR1) in healthy populations was replicated, reinforcing the influence of the SNP rs2814778 (T>C) in WBC count. Genetics plays an important role in regulating WBC count in patients with SCD. Our results point to possible mechanisms involved in WBC count variation and as increased WBC count is associated with more severe SCD, these results could suggest potential therapeutic targets for individuals with SCD.

Effects of Hemorrhage on Hematopoietic Cell Depletion after a Combined Injury with Radiation: Role of White Blood Cells and Red Blood Cells as Biomarkers.

Combined radiation with hemorrhage (combined injury, CI) exacerbates hematopoietic acute radiation syndrome and mortality compared to radiation alone (RI). We evaluated the effects of RI or CI on blood cell depletion as a biomarker to differentiate the two. Male CD2F1 mice were exposed to 8.75 Gy γ-radiation (60Co). Within 2 h of RI, animals were bled under anesthesia 0% (RI) or 20% (CI) of total blood volume. Blood samples were collected at 4-5 h and days 1, 2, 3, 7, and 15 after RI. CI decreased WBC at 4-5 h and continued to decrease it until day 3; counts then stayed at the nadir up to day 15. CI decreased neutrophils, lymphocytes, monocytes, eosinophils, and basophils more than RI on day 1 or day 2. CI decreased RBCs, hemoglobin, and hematocrit on days 7 and 15 more than RI, whereas hemorrhage alone returned to the baseline on days 7 and 15. RBCs depleted after CI faster than post-RI. Hemorrhage alone increased platelet counts on days 2, 3, and 7, which returned to the baseline on day 15. Our data suggest that WBC depletion may be a potential biomarker within 2 days post-RI and post-CI and RBC depletion after 3 days post-RI and post-CI. For hemorrhage alone, neutrophil counts at 4-5 h and platelets for day 2 through day 7 can be used as a tool for confirmation.

White blood cell counts can predict 4-year cardiovascular disease risk in patients with stable coronary heart disease: a prospective cohort study.

The prevalence of cardiovascular disease has increased sharply in the Asian population, and evaluation of the risk of cardiovascular events with stable coronary heart disease remains challenging. The role of white blood cell (WBC) count in assisting clinical decision-making in this setting is still unclear. This study sought to evaluate the prognostic meaning of WBC count among patients with stable coronary heart disease. This study included Asian participants (n = 1,933) from the prospective STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial, which involved 15,828 patients with stable coronary heart disease with 3-5 years of follow-up on optimal secondary preventive treatment. WBC count was measured at baseline. Associations between WBC count and cardiovascular outcomes were evaluated by Cox regression analyses with multivariable adjustments. Hematologic emergencies in patients may introduce potential bias. In the lower WBC count quartiles, patients had lower-risk clinical profiles. Higher WBC counts were associated with greater event probabilities for cardiovascular death, major cardiovascular events, or all-cause death. In Cox regression models, WBC counts were an independent predictor of major adverse cardiovascular events (OR = 2.445, 95% CI 1.427-4.190, P = 0.001) for the primary outcomes. For the secondary outcomes, including the composite of all-cause death, cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure, WBC counts were significantly predictive of events with similar magnitude (OR = 1.716, 95% CI 1.169-2.521, P = 0.006). In patients with stable coronary heart disease, higher WBC counts were associated with a heightened risk for the primary or secondary outcomes. https://clinicaltrials.gov/; Unique identifier NCT00799903.

Inflammation mediates the effect of adiposity and lipid metabolism indicators on the embryogenesis of PCOS women undergoing in vitro fertilization/intracytoplasmic sperm injection.

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine and metabolic disease affecting women of reproductive age. The low-grade chronic inflammation in PCOS is considered to be associated with obesity and dyslipidemia. We aim to investigate the potential mediating role of white blood cell (WBC) count, a representative inflammatory marker, in the effect of adiposity and lipid metabolism indicators on IVF/ICSI outcomes in PCOS women. We conducted a retrospective cohort study of 1,534 PCOS women who underwent their first IVF/ICSI cycles with autologous oocytes at a reproductive center from January 2018 to December 2020. The associations between PCOS women's adiposity and lipid metabolism indicators and WBC count and IVF/ICSI outcomes were examined using multivariable generalized linear models. Mediation analyses were conducted to evaluate the possible mediating role of WBC count. We found significant dose-dependent correlations between adiposity and lipid metabolism indicators and IVF/ICSI outcomes (i.e., hormone levels on the ovulatory triggering day, oocyte development outcomes, fertilization, early embryo development outcomes, and pregnancy outcomes) (all p < 0.05), as well as between adiposity and lipid metabolism indicators and WBC count (all p < 0.001). Increasing WBC count was associated with adverse oocyte and embryonic development outcomes (all p < 0.05). Mediation analyses suggested that increasing serum TG and LDL-C levels and decreasing serum HDL-C level were significantly associated with reduced high-quality Day 3 embryo count in PCOS women, with 21.51%, 9.75%, and 14.10% mediated by WBC count, respectively (all p < 0.05). We observed significant associations between lipid metabolism indicators and high-quality Day 3 embryo count in PCOS women, partially mediated by inflammation-related mechanisms, suggesting the potential intervention target for improving embryo quality in PCOS women.

Leukopenia in autosomal dominant polycystic kidney disease: a single-center cohort of kidney transplant candidates with post-transplantation follow-up.

Autosomal dominant polycystic kidney disease (ADPKD) has occasionally been associated with lower peripheral white blood cell (WBC) counts. This study aimed to investigate the peripheral blood cell counts in a large cohort of kidney transplant recipients before and after kidney transplantation and its potential impact on post-transplant outcomes. This was a retrospective study with long-term follow-up data of 2090 patients who underwent a first kidney transplantation in the Leuven University Hospitals, of whom 392 had ADPKD. In total, 2090 patients who underwent a first kidney transplantation in the Leuven University Hospitals were included, of whom 392 had ADPKD. Both pre- and post-transplantation, ADPKD patients had significantly lower total WBC counts, and more specifically lower neutrophil, lymphocyte and eosinophil counts compared with the non-ADPKD patients. This observation was independent of potential confounders such as level of inflammation, smoking habit, vitamins and pre-transplant medication. Overall survival and kidney transplant survival were significantly better in ADPKD vs non-ADPKD transplant recipients and a longer time to first infection was observed. However, no association between blood cell counts and outcome differences was found. In conclusion, this large single-center study reports a strong and independent association between ADPKD and lower peripheral WBC counts both before and after kidney transplantation. Considering the role of inflammation in disease progression, further investigation into the role of WBC in ADPKD is needed.

Investigating the relationship between haematological parameters and metabolic syndrome: A population-based study.

Metabolic syndrome (MetS) is a global public health concern. Chronic inflammation plays a role in MetS; haematological inflammatory parameters can be used as MetS predicting factors. Hereditary and environmental factors play an important role in the development of MetS. This study aimed to determine the relationship between haematological parameters and MetS in the adult population of southeastern Iran, Kerman. This cross-sectional study was a sub-analysis of 1033 subjects who participated in the second phase of the Kerman Coronary Artery Disease Risk Factor Study (KERCADRS). Metabolic syndrome was diagnosed according to Adult Treatment Panel III (ATP III) definition. Pearson correlation coefficient was used to investigate the relationship between haematological parameters with age and components of metabolic syndrome. The role of WBC, neutrophil, lymphocyte and monocyte in predicting metabolic syndrome was evaluated using the receiver operating characteristic (ROC) curve. White blood cell (WBC) and its subcomponent cells count, red cell distribution width (RDW), monocyte to HDL ratio (MHR) and Neutrophil to HDL ratio (NHR) had a significant positive correlation with the severity of MetS. The cut-off value of WBC was 6.1 (×103 /μL), the sensitivity was 70%, the specificity was 52.9% for females, the cut-off value of WBC was 6.3 (×103 /μL), the sensitivity was 68.2% and the specificity was 46.7%, for males. WBC and its subcomponent count, RDW, MHR and NHR parameters are valuable biomarkers for further risk appraisal of MetS in adults. These markers are helpful in early diagnoses of individuals with MetS.

Investigation of white blood cell characteristics in cerebrospinal fluid samples at pediatric brain tumor diagnosis.

The role of white blood cells (WBC) in the pediatric central nervous system (CNS) tumor microenvironment is incompletely defined. We hypothesized that the WBC profile in cerebrospinal fluid (CSF) correlates with the presence of tumor cells and prognosis in pediatric CNS tumors, as well as other patient and disease characteristics, and differs by tumor type, thus giving insight into the tumor immune response. We conducted a retrospective analysis of CSF WBC profiles at CNS tumor diagnosis in 269 patients at our institution. We examined total nucleated cell count, absolute counts, and percentages by WBC subtype. We compared CSF WBC values by tumor cell presence, patient vital status, tumor location, and the most common tumor types. Patients who died of their tumor had a lower CSF lymphocyte percentage and a higher absolute monocyte count in CSF at diagnosis. The presence of tumor cells in CSF was associated with fewer lymphocytes and monocytes. Ventricular tumors had higher CSF lymphocyte, monocyte, macrophage, and total nucleated cell counts than extraventricular tumors. Germ cell tumors, low-grade glioma, high-grade glioma, and ependymoma had lower macrophage counts or percentages compared to other tumor types. WBC profile in CSF at pediatric CNS tumor diagnosis correlates with patient prognosis and presence of metastatic cells, along with tumor type and other tumor characteristics like relationship to the ventricles. Prospective CSF profiling and study may be useful to future immunotherapy and other pediatric CNS tumor clinical trials.

Value of neutrophil-lymphocyte ratio in evaluating response to percutaneous catheter drainage in patients with acute pancreatitis.

BACKGROUNDEarly prediction of response to percutaneous catheter drainage (PCD) of necrotic collections in acute pancreatitis (AP) using simple and objective tests is critical as it may determine patient prognosis. The role of white blood cell (WBC) count and neutrophil-lymphocyte ratio (NLR) has not been assessed as a tool of early prediction of PCD success and is the focus of this study.AIMTo assess the value of WBC and NLR in predicting response to PCD in AP.METHODSThis retrospective study comprised consecutive patients with AP who underwent PCD between June 2018 and December 2019. Severity and fluid collections were classified according to the revised Atlanta classification and organ failure was defined according to the modified Marshall Score. WBC and NLR were monitored 24 h prior PCD (WBC-0/NLR-0) and 24 h (WBC-1/NLR-1), 48 h (WBC-2/NLR-2) and 72 h (WBC-3/NLR-3) after PCD. NLR was calculated by dividing the number of neutrophils by the number of lymphocytes. The association of success of PCD (defined as survival without the need for surgery) with WBC and NLR was assessed. The trend of WBC and NLR was also assessed post PCD.RESULTSOne hundred fifty-five patients [median age 40 ± 13.6 (SD), 64.5% males, 53.5% severe AP] were included in the final analysis. PCD was done for acute necrotic collection in 99 (63.8%) patients and walled-off necrosis in 56 (36.1%) patients. Median pain to PCD interval was 24 ± 69.89 d. PCD was successful in 109 patients (group 1) and 46 patients (group 2) who failed to respond. There was no significant difference in the baseline characteristics between the two groups except the severity of AP and frequency of organ failure. Both WBC and NLR showed an overall decreasing trend. There was a significant difference between WBC-0 and WBC-1 (P = 0.0001). WBC-1 and NLR-1 were significantly different between the two groups (P = 0.048 and 0.003, respectively). The area under the curve of WBC-1 and NLR-1 for predicting the success of PCD was 0.602 and 0.682, respectively. At a cut-off value of 9.87 for NLR-1, the sensitivity and specificity for predicting the success of PCD were calculated to be 75% and 65.4% respectively.CONCLUSIONWBC and NLR can be used as simple tests for predicting response to PCD in patients with acute necrotizing pancreatitis.

White Blood Cell Count Nadir and Duration of Aplasia Do Not Associate with Treatment Outcome in Adult Patients with Acute Myeloid Leukemia Undergoing Intensive Chemotherapy

Introduction: Adult patients with acute myeloid leukemia (AML) are usually treated with intensive chemotherapy, leading to prolonged bone marrow aplasia. It is usually assumed that a short duration of aplasia could be a surrogate marker of poor therapeutic efficacy in clearing bone marrow blasts, especially in older patients. No studies have evaluated the usefulness of such a surrogate marker in younger AML patients treated with intensive chemotherapy. Materials and Methods: In the present study, we retrospectively assessed the role of white blood cell (WBC) count nadir and duration of aplasia in 68 patients with AML treated with intensive chemotherapy and potentially candidate to stem cell transplantation. Results: The median (interquartile range) bone marrow aplasia was 25 days, and the mean WBC count nadir from chemotherapy start was at day +12, whereas the median neutrophil recovery occurred at day +24. No significant differences were found between responders and nonresponders for mean aplasia duration (25 vs. 26 days, p value = 0.76), mean WBC count nadir (12 vs. 12 days, p value = 0.86), and median neutrophil recovery (24 vs. 24, p value = 0.67). Discussion: The present study evaluated the potential prognostic role of WBC count nadir and duration of aplasia, demonstrating that they are not associated with treatment outcomes in adult patients with AML treated with intensive chemotherapy. Therefore, a short duration of aplasia seems not linked to poor therapeutic efficacy in clearing bone marrow blasts. Our findings, although needing validation in larger and more homogeneous cohorts, may offer helpful clues in the management of aplasia of AML patients.

Can leukocytosis foresee hysterectomy for placenta previa?

Aim: The frequency of placenta previa (PP) is increasingly rising due to the increase in caesarean ratio. The aim of this study is to investigate the role of the white blood cell (WBC) in the preoperatively taken complete blood specimen in foreseeing whether hysterectomy will be performed or not in patients with placenta previa totalis.Materials and Methods:Two hundred fifty-seven (257) patients who experienced caesarean due to placenta previa totalis (PPT) in Ondokuz Mayis University between 2010 and 2018 had been surveyed retrospectively. The results of the preoperative Complete Blood Count (CBC) of the Placenta PreviaTotalis (PPT) patients in which either hysterectomy was applied or not, demographic characteristics, other follow-up and treatment results were accessed via system records and file surveys. The primary outcome is the role of preoperative White Blood Cell (WBC) levels in predicting hysterectomy, Results: WBC median values in the pre-operative complete blood specimen of the patients with placenta previa totalis demonstrate difference between the patients with hysterectomy and those without hysterectomy. While the median value was as 9.7 109/L in the patients who could be recovered with treatments apart from hysterectomy, this was obtained as 11.3109/L in the patients in which hysterectomy was applied (p=0.007).Conclusion: Increase in WBC in the pre-operative blood specimen of the patients with diagnosis of Placenta Previa Totalis may be guiding whether hysterectomy will be applied or not.Keywords: Placenta previa; hysterectomy; leukocytosis; caesarean.

Quantifying Platelet Margination in Diabetic Blood Flow

Patients with type 2 diabetes mellitus (T2DM) develop thrombotic abnormalities strongly associated with cardiovascular diseases. In addition to the changes of numerous coagulation factors such as elevated levels of thrombin and fibrinogen, the abnormal rheological effects of red blood cells (RBCs) and platelets flowing in blood are crucial in platelet adhesion and thrombus formation in T2DM. An important process contributing to the latter is the platelet margination. We employ the dissipative particle dynamics method to seamlessly model cells, plasma, and vessel walls. We perform a systematic study on RBC and platelet transport in cylindrical vessels by considering different cell shapes, sizes, and RBC deformabilities in healthy and T2DM blood, as well as variable flowrates and hematocrit. In particular, we use cellular-level RBC and platelet models with parameters derived from patient-specific data and present a sensitivity study. We find T2DM RBCs, which are less deformable compared to normal RBCs, lower the transport of platelets toward the vessel walls, whereas platelets with higher mean volume (often observed in T2DM) lead to enhanced margination. Furthermore, increasing the flowrate or hematocrit enhances platelet margination. We also investigated the effect of platelet shape and observed a nonmonotonic variation with the highest near-wall concentration corresponding to platelets with a moderate aspect ratio of 0.38. We examine the role of white blood cells (WBCs), whose count is increased notably in T2DM patients. We find that WBC rolling or WBC adhesion tends to decrease platelet margination due to hydrodynamic effects. To the best of our knowledge, such simulations of blood including all blood cells have not been performed before, and our quantitative findings can help separate the effects of hydrodynamic interactions from adhesive interactions and potentially shed light on the associated pathological processes in T2DM such as increased inflammatory response, platelet activation and adhesion, and ultimately thrombus formation.

Role of White Blood Cells in Blood- and Bone Marrow-Based Autologous Therapies.

There has been significant debate over the role of white blood cells (WBCs) in autologous therapies, with several groups suggesting that WBCs are purely inflammatory. Misconceptions in the practice of biologic orthopedics result in the simplified principle that platelets deliver growth factors, WBCs cause inflammation, and the singular value of bone marrow is the stem cells. The aim of this review is to address these common misconceptions which will enable better development of future orthopedic medical devices. WBC behavior is adaptive in nature and, depending on their environment, WBCs can hinder or induce healing. Successful tissue repair occurs when platelets arrive at a wound site, degranulate, and release growth factors and cytokines which, in turn, recruit WBCs to the damaged tissue. Therefore, a key role of even pure platelet-rich plasma is to recruit WBCs to a wound. Bone marrow contains a complex mixture of vascular cells, white blood cells present at much greater concentrations than in blood, and a small number of progenitor cells and stem cells. The negative results observed for WBC-containing autologous therapies in vitro have not translated to human clinical studies. With an enhanced understanding of the complex WBC biology, the next generation of biologics will be more specific, likely resulting in improved effectiveness.

Macrophages contribute to the pathogenesis of sclerosing cholangitis in mice

Macrophages contribute to liver disease, but their role in cholestatic liver injury, including primary sclerosing cholangitis (PSC), is unclear. We tested the hypothesis that macrophages contribute to the pathogenesis of, and are therapeutic targets for, PSC. Immune cell profile, hepatic macrophage number, localization and polarization, fibrosis, and serum markers of liver injury and cholestasis were measured in an acute (intrabiliary injection of the inhibitor of apoptosis antagonist BV6) and chronic (Mdr2-/- mice) mouse model of sclerosing cholangitis (SC). Selected observations were confirmed in liver specimens from patients with PSC. Because of the known role of the CCR2/CCL2 axis in monocyte/macrophage chemotaxis, therapeutic effects of the CCR2/5 antagonist cenicriviroc (CVC), or genetic deletion of CCR2 (Ccr2-/- mice) were determined in BV6-injected mice. We found increased peribiliary pro-inflammatory (M1-like) and alternatively-activated (M2-like) monocyte-derived macrophages in PSC compared to normal livers. In both SC models, genetic profiling of liver immune cells identified a predominance of monocytes/macrophages; immunohistochemistry confirmed peribiliary monocyte-derived macrophage recruitment (M1>M2-polarized), which paralleled injury onset and was reversed upon resolution in acute SC mice. PSC, senescent and BV6-treated human cholangiocytes released monocyte chemoattractants (CCL2, IL-8) and macrophage-activating factors in vitro. Pharmacological inhibition of monocyte recruitment by CVC treatment or CCR2 genetic deletion attenuated macrophage accumulation, liver injury and fibrosis in acute SC. Peribiliary recruited macrophages are a feature of both PSC and acute and chronic murine SC models. Pharmacologic and genetic inhibition of peribiliary macrophage recruitment decreases liver injury and fibrosis in mouse SC. These observations suggest monocyte-derived macrophages contribute to the development of SC in mice and in PSC pathogenesis, and support their potential as a therapeutic target. Primary sclerosing cholangitis (PSC) is an inflammatory liver disease which often progresses to liver failure. The cause of the disease is unclear and therapeutic options are limited. Therefore, we explored the role of white blood cells termed macrophages in PSC given their frequent contribution to other human inflammatory diseases. Our results implicate macrophages in PSC and PSC-like diseases in mice. More importantly, we found that pharmacologic inhibition of macrophage recruitment to the liver reduces PSC-like liver injury in the mouse. These exciting observations highlight potential new strategies to treat PSC.

Serum procalcitonin level in monitorization of surgical site infections in neonates

A retrospective study was performed to evaluate the role of white blood cell (WBC), C-reactive protein (CRP) and procalcitonin (PCT) levels in the follow- up and treatment of surgical site infections (SSI) in neonates. Neonates who underwent surgical intervention (n:34) were evaluated for gestational age, sex, diagnosis, inflammatory markers (WBC, CRP, PCT), clinical findings, results of cultures and response to antimicrobial treatment. Records of 34 neonates and 36 surgical interventions were included to the study. Twenty (58.8%) of patients had SSI. Postoperatively CRP, WBC and PCT levels were increased (77%, 77%, 77% respectively) in patients with SSI. Postoperatively CRP, and WBC levels were increased (57% and 64% respectively) in patients without SSI. In conclusion, CRP levels and WBC count were significantly increased in 77% of cases after surgery. Increased PCT levels were detected only in patients with SSI. PCT levels may be considered as the most valuable marker to monitor SSI in neonates after surgery.

The role of red blood cells and cell-free hemoglobin in the pathogenesis of ARDS

The primary focus of research into the pathophysiology of the acute respiratory distress syndrome (ARDS) has been on the interaction between the lung, underlying causes of ARDS, and the role of white blood cells and platelets in contributing to lung injury. Given a lack of specific therapies for this common complication of critical illness, further insight into the pathophysiology of this syndrome is greatly needed to develop targeted interventions. The red blood cell (RBC) has been reported to undergo deleterious changes in critical illness and be present in the alveoli of patients with ARDS. Release of RBC contents is known to be injurious in other conditions but has only recently been studied in critical illness and ARDS. The contribution of the RBC to ARDS represents a new avenue of research that may produce new, targeted therapies for this deadly syndrome.

Changes In Cell-Derived Plasma Microparticles During The Acute Chest Syndrome In Children With Sickle Cell Disease

IntroductionMicroparticles (MP) are small (less than 1 µm), membrane-derived extracellular vesicles produced following cellular activation or apoptosis. They have been implicated as causative in a wide variety of pro-inflammatory diseases. Sickle cell disease is a hemoglobinopathy characterized by chronic hemolysis and systemic inflammation which can be complicated by vaso-occlusive pain crises (VOC) or the acute chest syndrome (ACS). Increasingly there is evidence that microparticles may play an important role in the pathophysiology of sickle cell disease. We hypothesize that plasma microparticles are elevated during ACS compared to VOC and baseline (resting). MethodsWhole blood was obtained under an approved consent from the Colorado Multiple Institution Review Board at the University of Colorado Denver, from three subjects with homozygous sickle cell disease (ages 4-18) at three distinct time points: baseline (resting) at routine clinic visits and upon hospitalization for VOC and ACS. The samples underwent differential centrifugation: plasma was isolated (5,000xg for 7 min at RT) and then cell free supernatant was separated (12,500xg for 6 min at 4°C). MPs were isolated by centrifugation at 17,000xg for 60 minutes at 4°C, and the MP pellet was resuspended in an equal volume of 1.25% human serum albumin. The samples were incubated with CD41 (PE)-, CD45 (PerCP-Cy5)-, and CD235 (FITC)-antibodies that are specific for MPs derived from platelets, leukocytes, and erythrocytes, respectively, and analyzed by flow cytometry. Statistics were performed using ANOVA with post-hoc Newman-Keuls test. ResultsThe amount of leukocyte-derived MP (WBC) measured during ACS was significantly higher (almost two-fold) than levels measured during baseline (resting) (p < 0.05), but not VOC. The erythrocyte (RBC) MP levels were also significantly elevated during ACS, compared to resting and VOC (p<0.05). There is a trend toward higher platelet (Plt) MP levels during ACS compared to both baseline and VOC, however this does not reach statistical significance likely due to the small sample size (n=3) (Fig. 1). In a separate analysis, the MPs from two patients admitted for VOC with evolution to ACS during the same hospitalization exhibited a three-fold increase in WBC MP levels during VOC that preceded their progression to ACS by 24-72 hours. [Display omitted] DiscussionMicroparticles may play a significant role in the pathophysiology of ACS in sickle cell disease. Leukocyte-derived MPs are elevated in ACS at higher levels than baseline. This likely reflects the important role of white blood cells (WBCs) in systemic inflammation and the importance of WBC-endothelial interactions in ACS. While platelet- and erythrocyte-derived MPs may be involved in ACS, a larger sample size will be needed to detect this effect. In addition, while hospitalized, two patients who had a similar magnitude increase in WBC MPs during VOC eventually progressed to ACS; thus, serial MP measurements could potentially serve as a biomarker to identify patients at risk for imminent development of ACS. Further prospective studies with larger sample sizes will be needed for validation. Future directions of study should also evaluate the role of endothelial-derived MPs and the role of ICAM-1. Disclosures:No relevant conflicts of interest to declare.

Correlation Of Longitudinal Blood Counts With Thromboembolic Complications In WHO 2008 Defined Prefibrotic Primary Myelofibrosis

Current treatment strategies in the classical Philadelphia- negative myeloproliferative diseases are challenged by the compelling evidence of the important role of white blood cell (WBC) counts for the risk of thrombosis (Barbui Blood 2013). Moreover, recent publications disclosed significant differences in regards of certain disease characteristics, vascular risk profiles and prognosis between WHO 2008 (Tefferi Blood 2007) classified essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (PMF) (Kvasnicka Am J Hematol 2008; Barbui JCO 2011; Buxhofer-Ausch Am J Hematol 2012). Hence, patients cohorts classified prior to WHO 2008 may likely consist of a mix of patients with ET and prefibrotic PMF. A recent analysis of the prior to WHO 2008 classified UK-PT1 cohort demonstrated, that not blood counts at diagnosis but enhanced longitudinal WBC counts measured during the course of the disease correlate with the risk of vascular complications in ET (Campbell Blood 2012).The current study aimed to correlate longitudinal blood counts with thromboembolic events in patients from our institution, all reclassified according to WHO 2008 as prefibrotic PMF.In 76 patients with a valid consensus diagnosis of prefibrotic PMF longitudinal blood counts including hemoglobin levels, WBC counts and platelet counts were collected retrospectively from the patient's records (most patients were followed every 3-4 months). Subsequently, these parameters along with certain disease specific and laboratory parameters were correlated with the incidence of major arterial or venous thrombosis after diagnosis by applying Cox-regression analyses.While overtime-platelet counts (mean 553.14±287.04) were significantly lower than baseline platelet counts (mean 806.61±372.51), WBC counts did not change over time (baseline mean 10.60±4.11; over-time mean 10.64±9.2). By correlating 1644 longitudinal blood counts with major venous and/ or arterial thromboembolic events after diagnosis neither a significant correlation of overtime- platelet counts with total thrombosis (p= 0.347) nor with arterial thrombosis (p= 0.516) was seen. In contrast, there was a clear statistical trend for correlation of over-time WBC counts with total thrombosis (p= 0.072) and- even more pronounced- with arterial thrombosis (p= 0.057). Comparison of these data to a cohort of 111 patients with WHO 2008 diagnosed ET will be presented.In conclusion our data presume an important role of over-time WBC counts on vascular events in patients with prefibrotic PMF. Apparently our current treatment strategies are not sufficient enough to lower WBC counts over- time. Appropriate medication for lowering WBC counts has to be implemented in future treatment concepts. Studies on larger, WHO 2008 diagnosed patient cohorts are needed to confirm and extend this important findings. Disclosures:Thiele:AOP Orphan Pharmaceuticals, Incyte, Novartis, Shire, Sanofi: Consultancy; Novartis, Shire: Research Funding; AOP Orphan Pharmaceuticals, Incyte, Novartis, Shire, Sanofi: Honoraria. Gisslinger:AOP Orphan Pharmaceuticals: Advisory Board Meeting Other, Honoraria; Novartis: Advisory Board Meeting, Advisory Board Meeting Other, Honoraria; Sanofi-Aventis: Advisory Board Meeting, Advisory Board Meeting Other, Honoraria; Shire: Advisory Board Meeting, Advisory Board Meeting Other, Honoraria; Celgene: Advisory Board Meeting Other, Honoraria; Janssen: Advisory Board Meeting, Advisory Board Meeting Other, Honoraria.

White Blood Cell Count in Women: Relation to Inflammatory Biomarkers, Haematological Profiles, Visceral Adiposity, and Other Cardiovascular Risk Factors

The role of white blood cell (WBC) count in pathogenesis of diabetes, cardiovascular disease, and obesity-related disorders has been reported earlier. Recent studies revealed that higher WBC contributes to atherosclerotic progression and impaired fasting glucose. However, it is unknown whether variations in WBC and haematologic profiles can occur in healthy obese individuals. The aim of this study is to further evaluate the influence of obesity on WBC count, inflammatory biomarkers, and metabolic risk factors in healthy women to establish a relationship among variables analyzed. The sample of the present study consisted of 84 healthy women with mean age of 35.56 +/- 6.83 years. They were categorized into two groups based on their body mass index (BMI): obese group with BMI > 30 kg/m2 and non-obese group with BMI < 30 kg/m2. We evaluated the relationship between WBC and platelet count (PLT) with serum interleukin 6 (IL-6), C-reactive protein (CRP), angiotensin pi (Ang pi), body fat percentage (BF %), waist-circumference (WC), and lipid profile. WBC, PLT, CRP, and IL-6 in obese subjects were significantly higher than in non-obese subjects (p < 0.05). The mean WBC count in obese subjects was 6.4 +/- 0.3 (x10(9)/L) compared to 4.4 +/- 0.3 (x10(9)/L) in non-obese subjects (p = 0.035). WBC correlated with BF% (r = 0.31, p = 0.004), CRP (r = 0.25, P = 0.03), WC (r = 0.22, p = 0.04), angiotensin 11 (r = 0.24, p = 0.03), triglyceride (r = 0.24, p = 0.03), and atherogenic index of plasma (AIP) levels (r = 0.3, p = 0.028) but not with IL-6. Platelet count was also associated with WC and waist-to-hip ratio (p < 0.05). Haemoglobin and haematocrit were in consistent relationship with LDL-cholesterol (p < 0.05). In conclusion, obesity was associated with higher WBC count and inflammatory parameters. There was also a positive relationship between WBC count and several inflammatory and metabolic risk factors in healthy women.

Role of white blood cell and neutrophil counts in predicting spontaneous stone passage in patients with renal colic

To determine the clinical, imaging and laboratory variables that can predict spontaneous passage of ureteral stones causing renal colic and the role of white blood cell (WBC) and neutrophil counts for the prediction of spontaneous calculi passage. A total of 156 patients who were referred to the emergency department complaining of renal colic due to a ureteral stone entered the analysis. Several clinical, laboratory and imaging parameters were evaluated for their potential ability to predict stone passage in a time interval of 1 month. The study design had two objectives. Primarily we analyzed all patients irrespective of stone size and secondly we analyzed patients with calculi of 10 mm maximum length. Spontaneous stone passage was observed in 96 (61.5%) patients in the overall population and in 84 (65.1%) of 129 patients with calculi <10 mm. Increased concentrations of serum WBCs and neutrophils at the time of the acute phase of a renal colic were associated with increased likelihood of spontaneous passage. In the multivariate analyses we found that WBC and neutrophil counts were the most important predictors of stone elimination. Active surveillance of patients suffering from ureteral lithiasis is an acceptable option. Identifying the parameters which can predict those patients who will mostly benefit from this is of great importance. Based on our results, WBC and neutrophil counts should be considered when patients with renal colic secondary to ureteral calculi are evaluated since they can significantly add to spontaneous elimination prediction. Their consideration in addition to other important factors, like stone size and location, would maximize their predictive ability.

Circulating white blood cells and platelets amplify oxidative stress in heart failure

Mitochondria of circulating white blood cells (WBC) and platelets sense oxidative stress during capillary passage and react by producing reactive oxygen species (ROS). Although evidence indicates that congestive heart failure (CHF) is associated with oxidative stress, the role of WBC and platelets as mediators in CHF has not been investigated. Patients with CHF (n = 15) and healthy volunteers (n = 9) were enrolled between 2006 and 2007 into this observational study. Arterial and venous blood samples from participants were incubated with probes to detect cytosolic and mitochondrial ROS. Fluorescence-activated cell sorting was used to measure the degree of fluorescence in WBC and platelets. Patients with CHF had a higher proportion of ROS-positive arterial WBC and platelets than did controls (67% +/- 47% versus 16% +/- 9%; P <0.005), as well as venous WBC and platelets (77% +/- 43% versus 38% +/- 13%; P <0.01). In the control group, the proportion of cytosolic ROS-positive arterial WBC and platelets was lower than that for ROS-positive venous WBC and platelets (16% +/- 9% versus 38% +/- 13%; P <0.005). CHF patients had a higher proportion of mitochondrial ROS-positive arterial and venous WBC and platelets than did controls. In CHF, the proportion of WBC and platelets that are ROS-positive is raised, possibly because cytosolic ROS-positive WBC and platelets are normally cleared in the lungs; this function is deficient in CHF while mitochondrial ROS production is increased. The raised numbers of circulating ROS-positive WBC and platelets amplify oxidative stress in CHF.