Higher Total White Blood Cell Counts Research Articles

Leukoaraiosis Mediates the Association of Total White Blood Cell Count With Post-Stroke Cognitive Impairment.

Background and PurposeThe inflammatory response could play a key role in cognitive impairment. However, there has been limited research into the association between total white blood cell (WBC) count and post-stroke cognitive impairment (PSCI), and the significance of leukoaraiosis (LA) in this relationship is unknown. We aimed to examine the total WBC count in relation to PSCI and whether this association was mediated by LA.MethodsConsecutive patients with first-ever ischemic stroke were prospectively enrolled from October 2020 to June 2021. The total WBC count was measured after admission. Cognitive function evaluations were performed at the 3-month follow-up using Mini-mental State Examination (MMSE). We defined the PSCI as an MMSE score <27.ResultsA total of 276 patients (mean age, 66.5 years; 54.7% male) were included in this analysis. Among them, 137 (49.6%) patients experienced PSCI. After adjustment for potential confounders, higher total WBC count was significantly correlated with an increased risk of LA [per 1-SD increase, odds ratio (OR), 1.39; 95% CI 1.06–1.82; p = 0.017] and PSCI (per 1-SD increase, OR, 1.51; 95% CI 1.12–2.04; p = 0.006). Furthermore, mediation analysis demonstrated that the association between total WBC count and PSCI was partly mediated by LA (the regression coefficient was changed by 9.7% for PSCI, and 12.4% for PSCI severity, respectively).ConclusionIncreased total WBC count is a risk factor for PSCI. The presence of LA was partially responsible for the PSCI in patients who had a higher total WBC count.

Elevated White Blood Cell Count Is Associated with an Increased Risk of Insulin Resistance among Non-Diabetic Taxi-Motorbike Drivers Working in Cotonou, Benin

High white blood cell count (WBC) and insulin resistance (IR) are interrelated events that contribute to non-communicable diseases (NCDs), including type-2 diabetes (T2D). However, associations between IR and hematological parameters have never been explored in populations of Benin. The aims of this study were to determine the prevalence of IR and associated hematological parameters in taxi-motorbike drivers (TMDs) working in Cotonou. A total of 133 participants were analyzed in this cross-sectional study. Complete blood count, including WBC and platelet, as well as fasting plasma glucose and insulin, were performed by standard procedures. IR was assessed using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Factors associated with IR, their odds ratios (ORs) and 95% confidence intervals (CIs) were determined by logistic regression analysis. The mean age of the study participants was 39.3 years. The HOMA-IR cut-off (75th percentile) for IR was 5.9. The overall prevalence of IR was 24.1%. IR increased with the increase of exposure duration and WBC levels. Logistic regression analysis revealed that the risk of IR increased significantly with higher total WBC, with adjusted ORs (95% CI) for the second and third tertiles of 3.56 (1.10 - 11.58) and 4.01 (1.21 - 13.31), respectively. Similar patterns of associations were observed in an analysis restricted to non-drinkers, although these estimates lacked statistical significance. BMI > 24.2 kg/m2 was independently associated with an increased risk of IR (OR = 3.82, 95% CI: 1.33 - 11.03, P = 0.013). In conclusion, the prevalence of IR in TMDs was 24.1%. IR was significantly associated with elevated WBC count and BMI. WBC may serve as a biomarker to identify individuals at the greatest IR risk.

Immunophenotypes and Clinical Outcomes in Adult Patients with Sickle Cell Disease: Lymphopenia Correlates with End Organ Damage

Introduction: Sickle cell disease (SCD) is the most prevalent inherited hemoglobinopathy in the United States. While the primary event is polymerization of HbS under deoxygenation in red cells, the contribution of white blood cells and inflammation to SCD pathology has been increasingly recognized. Prior investigations of lymphocytes in SCD revealed varied abnormalities some of which have been shown to be corrected by hydroxyruea (HU) though not uniformly (Nickel 2015, Allali 2019). Alterations in lymphocyte subsets have previously been correlated with survival in elderly populations (Ferguson 1995) and with non-AIDS related mortality in HIV (Helleberg 2014). The aim of this study was to analyze alterations of leukocyte populations in relation to different clinical outcomes in a large set of adult patients with sickle cell disease at steady state. Methods: Patients were consented and data was obtained as part of the INSIGHTS study (NCT02156102). Only patients with HBSS/Sβ0 from whom lymphocyte subset panels had been prospectively collected were included in this analysis. Panels consisted of total CD3+ T cells, CD4+/CD8- (CD4+) and CD8+/CD4- (CD8+) T cells, CD19+ B cells and CD16/56+ NK cells; absolute neutrophil count (ANC), white blood cell count (WBC), CD4/CD8 and ANC/ALC (absolute lymphocyte count) ratios were examined as well. Patients were classified as having cardiovascular events (CVE) if they reported prior stroke, pulmonary embolism, deep vein thrombosis, myocardial infarction, arrhythmia, cardiomyopathy, coronary artery bypass or stent. Ulcer status was defined as history of, or current active cutaneous lower extremity ulcer. Also analyzed were self-reported pulmonary hypertension (pHTN), diabetes mellitus (DM), and a combined End Organ Damage Score (EODS) consisting of one point for each of the following clinical outcomes: CVA, Any Ulcer, pHTN, CAD (MI/CABG/stent), cardiomyopathy, PE/DVT, DM. Multivariate analysis was performed controlling for age, gender and active HU use and Spearman correlation coefficients were calculated using SAS software. Results: 170 patients were included in this analysis, 54.7% female, mean age of 38.7 years, 95.3% HbSS, 64.1% on active HU treatment, and 15.9% chronically transfused. Mean leukocyte counts were within reference ranges except for CD19+ cells (666 c/uL) which were double the upper limit of normal (ULN 321 c/uL) consistent with prior reports. The 40% of patients with a CVE history showed an overall decrease in their lymphocyte populations (CD3+, CD4+, CD8+, CD19+) and WBC compared to those without (Table 1). Patients with a pHTN history (15.3%) had lower total CD3+, CD8+, CD19+, ANC's and WBC's. This resulted, somewhat surprisingly, in a significantly lower ANC/ALC ratio than in those patients without pHTN. No significant correlations with organ damage outcomes were noted for CD4/CD8 ratios or NK cells. Similar to the CVE findings, increased EODS was associated with significantly lower total T lymphocytes, CD4+, CD8+, and CD19+ cells while ANC/ALC ratio was significantly increased (Tables 2 &amp; 3). DM is very rare overall in SCD and was in our adult population (2/170) as well (Morrison 1979). It is notable that these 2 patients had significantly lower overall T and B cells and elevated ANC/ALC ratios. Compared to patients without any history of cutaneous ulcer, those with active ulcers had significantly lower total T cells (CD3+) and CD8+ cells (Table 4) while higher total WBC was seen in patients with a history of but no active ulcer compared to those without an ulcer history. Discussion: Our analysis of a large cohort of adult SCD patients at steady state revealed significant alterations in leukocyte populations in relation to a variety of clinical events. The salient finding was that B and T cell lymphocyte populations were significantly decreased in relation to clinical outcomes such as CVE and pHTN. The potential impact of this finding is highlighted by the adverse survival outcomes associated with lymphopenia seen in studies of general adult populations and in those with other medical problems such as cancer (Zidar 2019, Ray-Coquard 2009). While the interpretation of this study is limited to correlations further follow-up and study of SCD immunophenotypes may reveal important prognostic information that could enhance future care strategies. Disclosures Minniti: Bluebird bio: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; CLS Bering: Consultancy; Roche: Consultancy, Research Funding; TauTona: Consultancy, Research Funding; Emmaus: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

Association between Obstructive Sleep Apnea and Cardiovascular Risk Factors: Variation by Age, Sex, and Race. The Multi-Ethnic Study of Atherosclerosis.

The association between obstructive sleep apnea (OSA) and cardiovascular disease (CVD) is complex, bidirectional, and may vary across groups. Understanding which cardiovascular risk factors vary in their relationship to OSA across population groups may improve knowledge of OSA-related CVD susceptibility. To better understand the heterogeneity of associations, we assessed whether associations of OSA with cardiovascular risk factors vary by age, sex, and race/ethnicity. We performed cross-sectional analyses of 1,344 Multi-Ethnic Study of Atherosclerosis participants who underwent overnight full polysomnography, assays of fasting blood, and assessments of cardiovascular risk factors. Risk factors considered were blood pressure, glucose/lipid concentrations, white blood cell (WBC) total and subset counts, and cystatin C. The outcome was the apnea-hypopnea index (AHI). Linear regression analyses with tests for interactions were conducted. The sample had a mean age of 68 ± 9 years. Forty-seven percent of the sample was male, and 32% had moderate or severe OSA (AHI, ≥15). Multivariable adjusted analysis showed significant associations between higher AHI with lower high-density lipoprotein cholesterol and higher diastolic blood pressure and neutrophil counts. Significant interactions with demographic factors were observed. Stronger associations were shown between AHI and higher total WBC count (Pint = 0.006) and glucose concentrations (Pint = 0.006) in younger (<65 yr) than in older individuals, higher triglyceride concentrations in men than in women (Pint = 0.006), and higher total WBC (Pint = 0.07) and monocyte counts (Pint = 0.03) in African American individuals than in other racial groups. In a multiethnic cohort, we found increased levels of cardiovascular risk factors in association with OSA, including elevated neutrophil counts, a marker of inflammation. Furthermore, several associations were stronger in men, younger individuals, and African American individuals, highlighting pathways for CVD risk that may explain heterogeneity in the associations between CVD and OSA across population groups.

Molecular Study of NPM1-A (Nucleophosmin1-A) Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters

Acute myeloid leukemia (AML) is a hematological malignancy of myeloid progenitor cells characterized by anomalous proliferation, inhibition of differentiation and expansion of leukemic cells blocked at the early stage of hematopoiesis. The molecular markers have become a smart tool to further division of AML patients into subgroups. Nucleophosmin (NPM1) mutations are found in approximately 30% of adult AML patients and are associated with a favorable outcome when detected in absence of FLT3-ITD mutation. Over 50 molecular NPM1 mutation variants have been identified; the most common one is NPM1-A mutation. The current study aims to detect; the frequency of NPM1-A in Iraqi adult newly diagnosed AML patients using real time – PCR technique and evaluate the relationship of NPM1-A with age, gender, total white blood cell (WBC) count and FAB subtypes of the disease. The frequency of NPM1-A mutation in newly diagnosed AML patients was 18.86%. Age was non-significantly higher in NPM1-A mutated patients than in patients without mutation (P=0.538). The NPM1-A mutation was predominantly seen in male (P= 0.069). The mutation was non-significantly higher among monocytic subtypes (M5+M4) compared with the other subtypes of the disease (P=0.916). In the NPM1 mutated group, the total WBC count was non-significantly higher than the non-mutated group (P=0.302). These findings suggest; Real time-PCR technique using TaqMan probe was very specific molecular test for this mutation. Mutated NPM1-A patients were associated with increased age, a higher total WBC count, male predominance and the monocytic subtypes of the disease.

A Human Intervention Trial: Effects of Fine Concentrated Ambient Particles on Cardiac Autonomic Dysfunction and Inflammation Are Mitigated by B Vitamin Supplementation

Background: Ambient fine particulate matter (PM2.5) pollution is a trigger of acute cardiovascular events. Individual-level preventions have been proposed to complement regulation in reducing the global burden of PM2.5–related cardiovascular diseases. We investigated whether B vitamins mitigate the acute effects of PM2.5 on cardiac autonomic dysfunction and inflammation. Methods: In a single-blind crossover intervention trial, we administrated placebo and then four-week B vitamin supplement (5 mg/d folic acid, 100 mg/d vitamin B6, and 1 mg/d vitamin B12) to ten healthy volunteers. Each volunteer received three two-hour controlled exposure experiments to medical air or PM2.5 (250μg/m3), in pre-determined order. We used electrocardiogram to measure resting heart rate (HR) and heart rate variability (HRV), and hematology analyzer to determine white blood cell (WBC) counts (pre-, post-, 24 h post-exposure). Results: Compared to medical air, PM2.5 exposure was associated with 3.8 bpm (95% CI, 0.3, 7.4; P=0.04) higher resting HR and 57.5% (95% CI, 2.5%, 81.5%; P=0.04) lower low-frequency power following exposure. PM2.5 exposure was associated with 11.5% (95% CI, 0.3%, 24.0%; P=0.04) higher total WBC count and 12.9% (95% CI, 4.4%, 22.1%; P=0.005) higher lymphocyte count 24 h post-exposure. These effects were mitigated by B vitamin supplementation – which attenuated the effect of PM2.5 on HR by 150% (P=0.003), low-frequency power by 90% (P=0.01), total WBC count by 139% (P=0.006), and lymphocyte count by 106% (P=0.02). Conclusions: In healthy adults, two-hour PM2.5 exposure substantially increases HR, reduces HRV, and increases WBC. These effects are reduced by four-week B vitamin supplementation.

Characterizing PML/RAR? Isoforms of Acute Promyelocytic Leukemia (APL) in Malay Patients

Aim: Reciprocal translocation between retinoic acid receptor alpha (RAR?) gene on chromo- some 17 and promyelocytic leukemia (PML) gene on chromosome 15 is the hallmark for acute promyelocytic leukemia (APL). Three different PML/RAR? isoforms have been described; S-form, L-form and V-form. Our aims were to characterize the different types of PML/RAR? iso- forms in Malay patients with APL and to determine the outcome of these different types of iso-forms. Materials and methods: RT-PCR analysis was performed on 20 patients recruited from hematology-oncology ward. RT-PCR detected fusion transcript of PML/RAR? in all patients. Results and Discussion: Of these patients, 65% (13 patients) exhibited L/V-form, and 35% (7 patients) S-form. Total white blood cell count (TWBC) was higher in L/V-form (25 x 109/l) compared to S-form (2.1 x 109/l) (p &lt; 0.05). Five years survival rate was 100% and 33.3% for L/V-forms and S-forms respectively (p&lt;0.005). Conclusion: We conclude that L/V- forms is the commonest isoform among Malays. They presented at younger age with higher TWBC counts. Although the sample size is small, our preliminary data showed an interestingly longer survival outcome among L/V-forms compared to S-form. PML/RAR? isoforms could be used in future as risk stratification feature in patients diagnosed as APL. Further study with more number of patients is required. DOI: http://dx.doi.org/10.3329/bjms.v13i3.15553 Bangladesh Journal of Medical Science Vol.13(3) 2014 p.311-315

Increment of absolute neutrophil count in the third trimester and increased risk of small-for-gestational-age birth: Hirakata Risk Associated with Pregnancy Assessment Research (HIRAPAR)

Small-for-gestational-age (SGA) infants, who have growth restriction, have higher perinatal morbidity and mortality. Excessive inflammatory reaction such as neutrophil activation has been observed in pregnant women whose offspring had restricted fetal growth, but the association between white blood cell (WBC) counts and SGA birth has not yet been assessed. We therefore examined the association of WBC count and its change with the risk of SGA birth. We enrolled 2356 pregnant women who had full-term singleton delivery at a private maternity hospital in Hirakata, Japan. SGA was defined as under the 10th percentile of birthweight for gestational age, baby sex, and mother's parity according to the Japanese neonatal anthropometric charts renewed in 2010. Blood samples were measured in the first and third trimesters. We performed multiple logistic regression analysis to assess associations between total and differential WBC counts and SGA birth. Women with SGA birth tended to have higher total WBC count in the third trimester compared with women who did not have SGA birth. This tendency was not observed for total WBC count in the first trimester. After adjustment for age, height, body mass index at entry, smoking habit, weekly gestational weight gain, and pregnancy-induced hypertension, higher total WBC count in the third trimester was associated with an increased risk of SGA birth. Total WBC count in the first trimester did not show any significant association with SGA birth. The ratio of total WBC count in the third trimester to that in the first trimester was associated with SGA birth; the odds ratio for 1 unit increase was 3.02 (95% CI: 1.54-5.92). Regarding differential WBC counts in the third trimester, neutrophil count but not lymphocyte count was associated positively with SGA birth. Higher total WBC and absolute neutrophil counts in the third trimester were associated with SGA birth. In addition, greater ratio of increase in total WBC counts during pregnancy showed a positive association with the incidence of SGA birth. These associations may reflect a vicious cycle of inflammation and placental dysfunction as a cause of fetal growth restriction.

White blood cell count and the metabolic syndrome in older Chinese: The Guangzhou Biobank Cohort Study

Aims To examine the association between white blood cell count (WBC) and metabolic syndrome (MS) in an older Chinese population. Methods Three thousand and twenty men and 7256 women aged 50–85 years were recruited and received a medical check-up including measurement of complete blood count, blood pressure, obesity indices, fasting total, LDL-, HDL-cholesterol, triglycerides, glucose and c-reactive protein (CRP). Information on socioeconomic and lifestyle factors was also collected. Results Vascular risk factors including waist circumference, body mass index, triglyceride, total-, LDL-cholesterol, CRP and systolic and diastolic blood pressures were all positively associated with WBC in both men and women ( p from 0.0085 to <0.001). The risk of MS increased significantly with higher total WBC, with adjusted odds ratios (95% confident interval) for second and third tertiles of 1.86 (1.43, 2.42), 2.56 (1.98, 3.32) in men and 1.67 (1.46, 1.90), 2.66 (2.34, 3.03) in women, respectively. Neutrophil and lymphocyte were strongly correlated with total WBC and showed similar association with the MS. Conclusion There is a strong relationship between total WBC, neutrophil and lymphocyte and the constellation of MS components and associated vascular risk in this older Chinese population.

Comparison of the effectiveness and complications of half and full doses of pegfilgrastim in breast cancer patients

11058 Background: Pegfilgrastim (G-CSF) is a longer half-life synthetic growth factor used to reduce the incidence of infection following myelosuppressive chemotherapy but is associated with bone pain and hypergranulocytosis. Little data exists regarding efficacy and possible reduced toxicity with lower doses. Methods: A retrospective review identified early stage breast cancer pts who received reduced doses of G-CSF. Data collected prior to and after each dose of G-CSF included total white blood cell count (WBC), absolute granulocyte count (AGC),patient age, type and dose of chemotherapy, and stage of breast cancer. The occurrence of fever and infection was compared between the full and reduced dose groups. Pts completed a Likert scale (1–5) rating bone pain after each dose of G-CSF. Results: Thirty four pts received adjuvant treatment including adriamycin-cyclophosphamide (AC) followed by taxane (T) in 12, dose dense AC-T in 13, other regimens in 9. The median age was 53 years (range of 36 to 82). Thirty-two pts initially received 6 mcg but were reduced to 3mcg due to drug toxicity. Two pts received only 3mcg doses. There was a significant difference in the WBC post chemotherapy for the 98 treatments with 6 mcg (8400 (3000–49,600) cells/cu mm (Median (Range)) versus 116 treatments with 3 mcg (7600 (3000–18,900) cells/cu mm (p&lt;0.02). There was no significant difference between the post chemotherapy AGC for the 6 mcg (6000 (2200–38,000) cells/cu mm versus the 3 mcg (5800 (1000–16,600) cells/cu mm. Six pts receiving 6 mcg had a post G-CSF WBC &gt; 20,000 cells/cu mm vs none receiving 3 mcg (Fisher exact test, p&lt;0.01). No WBC &lt; 2,000 cells/cu mm or neutropenia of &lt;1000 cells/cu mm was noted with either regimen. Reported fever and infection was not significantly different between the 6 and 3 mcg doses (Fever: 6 mcg 3/98 (3.1%) vs 3 mcg 5/116 (4.3%); Infections: 6 mcg 5/98 (5.1%) vs 3 mcg 7/116 (6.0%)). Bone pain was more severe after 6 mcg dose than the 3 mcg dose (P &lt; 0.02). Conclusions: Although 6 mcg G-CSF was associated with a significantly higher total WBC, pts receiving 3 mcg G-CSF did not experience a difference in incidence of fever, infections, or neutropenia. However, lower doses were associated with significantly less bone pain and hypergranulocytosis. No significant financial relationships to disclose.