Decrease In White Blood Cell Count Research Articles

Hematology reference intervals for adult cows in France using the Sysmex XT-2000iV analyzer

In order to develop bovine hematology reference intervals (RIs) in accordance with new international recommendations, we analyzed 156 blood specimens of healthy adult dairy and beef cows from 32 farms with a Sysmex XT-2000iV analyzer, and by manual scoring of platelet clumps and white blood cell (WBC) differential. We established RIs by the nonparametric method, and examined effects of age, production type (beef vs. dairy), and stage of lactation. RIs could not be determined for platelet count and indices because clumps were observed in 80% of specimens. Optical and impedance red blood cell (RBC) counts were similar, although statistically different. RIs for analyzer and manual WBC differentials were not different except for lymphocyte concentration, the subpopulations of which were counted manually. Hematocrit was higher in beef than dairy cattle, and hemoglobin was lower in early lactation. Increases in RBC count, mean corpuscular volume, mean corpuscular hemoglobin, and RBC distribution width were noted with increasing age, along with decreases in WBC count, neutrophils, and lymphocytes. Most RIs in our study, with the exception of neutrophils, were similar to those previously reported using a flow cytometry analyzer.

Low-Level Light Therapy Protects Red Blood Cells Against Oxidative Stress and Hemolysis During Extracorporeal Circulation.

Aim: An activation of non-specific inflammatory response, coagulation disorder, and blood morphotic elements damage are the main side effects of the extracorporeal circulation (ECC). Red-to-near-infrared radiation (R/NIR) is thought to be capable of stabilizing red blood cell (RBC) membrane through increasing its resistance to destructive factors. We focused on the development of a method using low-level light therapy (LLLT) in the spectral range of R/NIR which could reduce blood trauma caused by the heart-lung machine during surgery.Methods: R/NIR emitter was adjusted in terms of geometry and optics to ECC circuit. The method of extracorporeal blood photobiomodulation was tested during in vivo experiments in an animal, porcine model (1 h of ECC plus 23 h of animal observation). A total of 24 sows weighing 90–100 kg were divided into two equal groups: control one and LLLT. Blood samples were taken during the experiment to determine changes in blood morphology [RBC and white blood cell (WBC) counts, hemoglobin (Hgb)], indicators of hemolysis [plasma-free hemoglobin (PFHgb), serum bilirubin concentration, serum lactate dehydrogenase (LDH) activity], and oxidative stress markers [thiobarbituric acid reactive substances (TBARS) concentration, total antioxidant capacity (TAC)].Results: In the control group, a rapid systemic decrease in WBC count during ECC was accompanied by a significant increase in RBC membrane lipids peroxidation, while in the LLLT group the number of WBC and TBARS concentration both remained relatively constant, indicating limitation of the inflammatory process. These results were consistent with the change in the hemolysis markers like PFHgb, LDH, and serum bilirubin concentration, which were significantly reduced in LLLT group. No differences in TAC, RBC count, and Hgb concentration were detected.Conclusion: We presented the applicability of the LLLT with R/NIR radiation to blood trauma reduction during ECC.

Leukapheresis in 15 patients weighing 20 kg or less: A single centre experience

The application of apheresis equipment to perform leukapheresis (LK) in low weight paediatric patients is logistically complex and lacking of largest clinical performing experiences, meanwhile, the benefit from LK is controversial. In this study, 15 children with acute lymphoblastic leukemia(ALL)and acute myeloid leukemia (AML) and hyperleukocytosis were treated with the COBE Spectra apheresis system in the general paediatric ward by the staff from the department of Blood Transfusion. 26 LK procedures were performed. 12 patients (80%) were performed with peripheral veins, others (20%) with femoral veins. Median age, body weight of the patients was 4 years (range from1year 10 month to 7 years) and 15kg (range from10 to 20kg). The median white blood cell (WBC) count of pre-first-LK was 289×109/L (range from 108×109/L to 579×109/L). The median decrease in WBC count after each LK was 34% (range from 14% to 54%), and overall decrease in WBC after completion of LK procedures was 45% (range from 15% to 70%). All of the patients had no further signs of leukostasis and achieved marked reductions in WBC counts. Only minor clinical adverse events were attributable to LK. With adequate monitoring and experienced team, LK is a safe and may be a beneficial leukoreduction method in small patients weighing 20kg or less with ALL and AML.

Pharmacokinetic Effect of Anti-tumor Necrosis Factor-alpha Agents on Thiopurine Drug Metabolism in Inflammatory Bowel Diseases

Introduction: Thiopurines and anti-tumor necrosis factor-alpha (anti-TNF) drugs are commonly used in treatment of inflammatory bowel diseases (IBD). Studies have established that thiopurines, when used in combination with anti-TNF drugs, affect the metabolism of anti-TNF drugs, resulting in higher serum drug concentrations. However, the data on the effect of anti-TNF drugs on thiopurine metabolism is limited. Methods: All adult IBD patients followed at our IBD center who had thiopurine metabolite concentrations measured between 2000-2016 were eligible for inclusion if they had at least 1 level measured while on thiopurine monotherapy, and 1 level measured while on combination therapy with an anti-TNF and thiopurine drug with the same thiopurine drug dose. Thiopurine metabolite concentration, white blood cell (WBC) count, mean corpuscular volume (MCV) and serum alanine aminotransferase (ALT) levels were compared on monotherapy and combination therapy. Paired t-test and Wilcoxon rank sum test were used for analysis of variables with normal and non-normal distribution, respectively. Results: 30 patients met the inclusion criteria (Table 1). Mean 6TGN level (in pmol/8 x 108 RBCs) on monotherapy and combination therapy were 201 and 267 respectively (% increase 33%; 95% CI 30.1-105.8; p 0.0004). There was a corresponding decrease in mean WBC count (in x1000/mL) from 7.6 to 6.1 (% decrease 20%; 95% CI 0.49-2.85; p 0.01) (Figure 1). There was no significant difference in 6-MMP levels, MCV and ALT levels on monotherapy and combination therapy (Table 2). On subgroup analysis, patients with therapeutic 6TGN levels >230 (n=13) had a significant increase in 6TGN levels (301 vs 369; p 0.03), and a corresponding decrease in WBC count (8.0 vs 5.7; p 0.07) on combination therapy. One patient developed leukopenia (WBC 2.8) after starting infliximab with an increase in 6TGN levels from 425 to 516.Figure: Thiopurine metabolite concentration and WBC count on monotherapy and combination therapy.Table: Table. Baseline CharacteristicsTable: Table. Lab parameters on monotherapy and combination therapyConclusion: In patients with IBD on thiopurine monotherapy, the addition of an anti-TNF agent can lead to an increase in 6-TGN concentration, thereby increasing the risk of leukopenia. Hence, elective thiopurine dose reduction should be considered prior to starting an anti-TNF agent, particularly in patients with therapeutic 6TGN concentration on thiopurine monotherapy. Our findings also suggest that benefits of combination therapy may be, in part, due to increase in thiopurine metabolite concentration with addition of an anti-TNF agent.

RITUXIMAB DELAYS WOUND HEALING AND DECREASES WHITE BLOOD CELL COUNT IN MALE MICE

ABSTRACTObjective: The aims of this research are to evaluate the effect of rituximab on wound healing, some hematological parameters, histological changes inwound healing, and histopathological changes in some organs in male mice.Methods: Totally, 15 adult male mice (25-30 g) were enrolled in this study. Animals were kept in the animal house College of Medicine/Universityof Babylon, and the temperature was controlled on 25°C and 14 hrs light and 10 hrs dark cycles. The animals were provided with standard diet andwater ad libitum. The animals were divided randomly into 3 groups, five mice in each group, Group 1 (control group) received no treatment, Group 2received rituximab 1 m/kg, IP, at days 0, 5, and 10 after wounding, in Group 3, rituximab was topically applied to the wound at days 0, 5, and 10 afterwounding.Results: The results yield that the wound healing significantly decreased (p<0.05) in Groups 2 and 3 as compared to control group. While the resultsregarding white blood cells (WBCs) count, there is a significant decrease in WBC count in Group 2 (p>0.05). Platelets and red blood cell count insignificantly increased in Group 3 as compared to control group (p<0.05). There were no histopathological changes in the skin, kidneys, and spleen.In liver, nonsignificant histopathological changes (p>0.05) found in Group 2 and 3 as compared to control group.Conclusion: Rituximab delays wound healing and reduces WBC count in male mice.Keywords: Rituximab, Wound healing, Lymphocyte, CD20, White blood cells, Mice.

Early platelet and leukocyte decline in patients with neuroinflammatory disorders after intravenous immunoglobulins.

Intravenous immunoglobulins (IVIGs) are a common therapy in patients with neuroinflammatory disorders, especially chronic inflammatory demyelinating polyradiculoneuropathy or Guillain-Barré syndrome. Hematological toxicities upon IVIG infusion are a known side effect and still an important subject of investigation. Laboratory results and data for clinical efficacy and tolerability of 62 patients with neuroinflammatory disorders treated with IVIG (0.4 g/kg bodyweight per day over 5 days) at the Department of Neurology, University of Duisburg-Essen, Germany, were retrospectively analyzed. Blood samples were taken before and 1 day after IVIG administration. In pre-treated and first-time treated patients, there was a significant decrease in white blood cell count (WBC) (8.10 ± 2.85/nl to 5.61 ± 2.50/nl, P < 0.001, n = 57) and platelets (255 ± 72/nl to 215 ± 66/nl, P < 0.001, n = 57). Mild hemolysis of red blood cells was found in patients who received IVIG for the first time (red blood cell count 4.61 ± 0.67/pl to 4.28 ± 0.52/pl, hemoglobin 13.7 ± 1.7 g/l to 13.0 ± 1.7 g/l, P < 0.001, n = 40). Hemolysis was associated with less tolerability of IVIG treatment and clinical efficacy was accompanied with a higher decline of WBC (not significant). Next to mild hemolysis, a significant decrease in WBC and platelets can be detected early after high dose IVIGs in patients with neuroinflammatory disorders. Changes in blood counts may be possible markers for clinical efficacy and tolerability. Patients with low blood counts in advance should be particularly closely monitored whilst on IVIG treatment.

NC-6004 Phase I study in combination with gemcitabine for advanced solid tumors and population PK/PD analysis

ObjectivesThis study was an open-label phase I study to confirm the safety and tolerability of NC-6004 in combination with gemcitabine in Japanese patients with advanced solid tumors and to assess the PK effects of NC-6004 monotherapy.MethodsThis phase I study used a 3 + 3 design to determine the maximum tolerated dose (MTD) and recommended dose of NC-6004 combined with gemcitabine. Safety and pharmacokinetics were assessed. The administration of NC-6004 alone was started at 60 mg/m2 every treatment cycle (21 days per cycle). From the second through eighth cycles, patients received NC-6004 in combination with 1000 mg/m2 of gemcitabine that was administered on day 1 and day 8 of each cycle, except for the first treatment cycle.ResultsTwelve patients with advanced solid tumors received 60 or 90 mg/m2 NC-6004. Both MTD and RD were determined to be 90 mg/m2. The most common drug-related adverse events were neutrophil decrease (66.7%) and white blood cell count decrease (41.7%). Population pharmacokinetic (PK) analysis revealed that NC-6004 PK profile in Japanese study was not significantly different from that in a previous Caucasian study.ConclusionsBoth MTD and RD of NC-6004 were determined to be 90 mg/m2. The pharmacodynamic (PD) model well explained the time course of estimated glomerular filtration rate (eGFR) and amplitude of decrease in eGFR. The decrease in eGFR appeared to reach saturation at >100 mg/m2 with NC-6004. Estimated probability of acute kidney injury on this PK/PD simulation was 30% with NC-6004 and 70% with cisplatin, which may better explain the renal toxicity profile.

Atrial natriuretic peptide protects against cisplatin-induced granulocytopenia.

Granulocytopenia is the major toxicity associated with cisplatin treatment. Atrial natriuretic peptide (ANP) is a cardiac hormone used clinically for the treatment of acute heart failure in Japan. ANP exerts a wide range of protective effects on various organs, including the heart, blood vessels, lungs, and kidneys. This study's objective was to investigate the protective effects of ANP on cisplatin-induced granulocytopenia in mice. The mice were divided into two groups: cisplatin with vehicle and cisplatin with ANP. ANP (1.5μg/kg/min via osmotic pump, subcutaneously) or vehicle administration was started 1day before cisplatin injection until the mice were killed. At 0, 2, 4, 8, and 14days after cisplatin injection (16mg/kg, intraperitoneally as a single dose), the white blood cell, red blood cell, and platelet counts were measured in the peripheral blood in both groups. The numbers of total and live cells and colony-forming unit-granulocyte-macrophage (CFU-GM) colonies in the bone marrow of the mice were also examined. In addition, at 0, 0.5, 1, and 2days after cisplatin injection, serum granulocyte colony-stimulating factor (G-CSF) levels were measured. ANP significantly attenuated the white blood cell count decrease in the peripheral blood 2 and 4days after cisplatin injection. ANP also attenuated the decrease in the number of live cells and CFU-GM colonies in bone marrow 2, 4, and 8days after cisplatin injection. ANP significantly increased serum G-CSF levels 1day after cisplatin injection. ANP has protective effects in cisplatin-induced granulocytopenia, with increased G-CSF production.

Dosimetric predictors of acute hematologic toxicity during concurrent intensity-modulated radiotherapy and chemotherapy for anal cancer

This study aimed at investigating whether the irradiated volume of pelvic bone marrow (PBM) and specific subsites may predict the occurrence of acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation. 50 patients, submitted to IMRT and concurrent chemotherapy, were analyzed. Several bony structures were defined on planning-CT: PBM and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. On dose-volume histograms, dosimetric parameters were taken. Endpoints included white blood-cell-count (WBC), absolute-neutrophil-count (ANC), hemoglobin (Hb) and platelet nadirs and acute hematologic toxicity (HT) according to RTOG scoring scale. Generalized linear modeling was used to find correlations between dosimetric variables and blood cell nadirs, while logistic regression analysis was used to test correlation with≥G3 HT. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the optimal cut-off points for predictive dosimetric variables with the Youden method. Maximum detected acute HT comprised 38% of≥G3 leukopenia and 32% of≥G3 neutropenia. Grade 2 anemia was observed in 4% of patients and≥G3 thrombocytopenia in 10%. On multivariate analysis a higher PBM-V 20 was associated with lower WBC nadir. Increased LSBM-V 40 was correlated with a higher likelihood to develop≥G3 HT. A cut-off point at 41% for LSBM-V 40 was found. Patients with LSBM-V 40≥41% were more likely to develop≥G3 HT (55.3 vs. 32.4%; p<0.01). Increased low-dose to pelvic bony structures significantly predicted for WBC decrease. Medium-high dose to specific osseous subsites was associated with a higher probability of HT. LSBM-V 40 was a strong predictor of≥G3 HT. A threshold at 41% for LSBM-V 40 could be used to limit HT.

Therapeutic effects of dendrosomal solanine on a metastatic breast tumor

AimsOur previous studies showed that alpha-solanine can inhibit tumor growth in cell culture and animal models of breast cancer. However, solanine is insoluble in common solvents; therefore, we developed a special nanoparticle with high-capacity solubility. The present study is aimed to deliberate the therapeutic effects of dendrosomal solanine (DNS) on a metastatic breast tumor in vitro and in vivo. Main methodsAfter DNS preparation and dosing procedures, forty-five mice were equally divided into five groups to investigate the anti-metastatic effects of DNS on mammary tumor-bearing mice. Key findingsCompared to solanine, DNS significantly suppressed the proliferation of 4 T1 cells in a dose- and time-dependent manner. DNS showed a remarkable safety rate of up to 10mg/kg. A significant decrease in white blood-cell count was seen at 20mg/kg DNS in comparison with control animals. Mice treated with DNS had smaller tumor volume (mm3) in comparison with control and solanine groups. Moreover, the incidence of the breast tumor metastases was about 67% in the control animals, where as solanine and DNS 1mg/kg were about 22% and 0%, respectively. Furthermore, the number of metastases per mouse varied from one to three. The tissues of tumor, brain, liver, spleen, and lung showed higher expression levels of Bcl-2 but lower expression levels of Bax, MMP-2, MMP-9, mTOR, and Akt in DNS-treated mice than control and solanine groups. SignificanceThe findings suggest that DNS has a more impactful therapeutic effect than solanine on 4 T1-induced breast tumorigenesis via influencing the tissue microenvironment.

The Effect of Ruxolitinib on White Blood Cell Counts in Patients with Polycythemia Vera: Results from the RESPONSE Trial

Background: Age, prior thrombotic events, and an elevated hematocrit are established risk factors for increased risk of thrombosis in patients with polycythemia vera (PV). Evidence also suggests that elevated white blood cell (WBC) counts ≥ 11×109/L are a significant independent risk factor for thrombosis in patients with PV (P =0.02; Barbui T, et al. Blood. 2015; 126:560-561). Therefore, this analysis was conducted to evaluate the impact of ruxolitinib (Rux) and best available therapy (BAT) treatment on WBC counts among patients with Baseline WBC counts ≥ 11×109/L in the RESPONSE trial. RESPONSE is a global, multicenter, open-label phase 3 trial investigating Rux and BAT in patients with PV who are resistant to or intolerant of hydroxyurea (HU). In the RESPONSE trial, Rux was associated with durable improvements in hematocrit control without phlebotomy compared with BAT as well as reductions in WBC counts.Methods: Changes from Baseline in WBC counts in the Rux arm (n=110), BAT arm (n=112), and HU subgroup of the BAT arm (n=66) were evaluated as part of an exploratory analysis using the RESPONSE 80-Week analysis dataset. Patient subgroups with Baseline WBC counts ≥ 11×109/L and < 11×109/L were analyzed for changes in WBC counts at Weeks 12, 32, and 80. For patients with Baseline WBC counts ≥ 11×109/L, the proportion of patients who achieved a decrease in WBC counts to ≤ 10×109/L or a ≥50% reduction at Week 12 and Week 32, respectively, was summarized; time to achieve the decrease was analyzed by Kaplan-Meier method.Results: Baseline mean WBC counts were generally similar among patients in the Rux arm, BAT arm, and HU subgroup (17.6×109/L, 19.0×109/L, and 17.4×109/L, respectively). The proportion of patients with Baseline WBC counts ≥ 11×109/L was also similar among the Rux arm, BAT arm, and HU subgroup (75%, 71%, and 70%, respectively). In patients with Baseline WBC counts ≥ 11×109/L, patients treated with Rux had greater mean reductions in WBC counts compared with the BAT arm and HU subgroups, and these reductions were maintained over time; mean changes from Baseline in WBC values at Week 12/Week 32 (×109/L) were -7.7/-7.2 for Rux, -3.2/-4.2 for BAT, and -1.2/-2.2 for HU. In patients with lower Baseline WBC counts, mean values remained stable over time. The change from Baseline to Week 12 for individual patients with Baseline WBC counts ≥ 11×109/L is shown in Figure 1. In patients with Baseline WBC counts ≥ 11×109/L, worsening WBC counts were observed in 10.8% of patients in the Rux arm vs 35.4% in the BAT arm (P =0.0002) and 47.8% in the HU subgroup (P <0.0001). In this same subgroup with elevated WBC counts, a greater proportion of patients in the Rux arm achieved WBC counts ≤ 10×109/L or a ≥50% reduction compared with the BAT arm or HU subgroup (Week 12: Rux, 41% vs BAT, 19% vs HU, 13%; Week 32: Rux, 45% vs BAT, 22% vs HU, 9%); median time to this reduction was 8 weeks in the Rux arm and was not reached in the BAT arm or HU subgroup.Conclusion: Rux treatment resulted in better control of WBC counts compared to BAT in patients with PV. These changes in the Rux arm occurred early after study initiation (within a median of 8 weeks) and were durable over time. Although RESPONSE was not powered to assess the impact of Rux on thromboembolic events, the lower rate of thromboembolic events observed in the Rux arm vs the BAT arm (1.8 vs 8.2 per 100 patient-years of exposure) is consistent with the observed effects of Rux on hematocrit, WBC counts, and C-reactive protein levels, which are all associated with thromboembolic risk. [Display omitted] DisclosuresMiller:Incyte Corporation: Honoraria, Research Funding. Kiladjian:Novartis: Other: Travel grant; Research Funding paid to institution (Hôpital Saint-Louis et Université Paris Diderot); Incyte Corporation: Consultancy; Novartis: Consultancy. Naim:Incyte Corporation: Employment, Equity Ownership. Sun:Incyte Corporation: Employment, Equity Ownership. Gadbaw:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Vannucchi:Baxalta: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire: Speakers Bureau.

A Comparison of Hematologic Parameters in Patients with Sickle Cell Disease Undergoing Red Cell Exchange Using Terumo BCT Spectra Optia and COBE Spectra Apheresis Systems

Introduction:Therapeutic red blood cell exchange (RBCX) is a process by which diseased red cells are replaced by healthy donor red blood cells. In patients with sickle cell disease, RBCX has been used to treat acute stroke, severe acute chest syndrome, multiorgan failure, priapism and splenic sequestration. It is also being used more commonly in the prevention of vaso-occlusive pain crises and for stroke prophylaxis for patients considered to be at high risk of stroke based on abnormal transcranial Doppler flow rates. In May 2014, we transitioned from the COBE Spectra apheresis system (Terumo BCT) to the next-generation Spectra Optia apheresis system (Terumo BCT) for all red cell exchange transfusions performed on our patients with sickle cell disease. A previous small study (n = 33 RBCX transfusions) compared the two instruments (Caridian BCT) and showed no difference between exchange volumes, processing time, pre and post-exchange hematocrit and HbS levels (Perseghin et al. Transfusion and Apheresis Science, 2013). However, other clinical parameters such as changes in white blood cell count and platelet counts were not examined. In order to determine if there were any differences in hematologic parameters between the 2 apheresis instruments, we measured the differences between pre and post-exchange HbS levels, white blood cell count (WBC), hematocrit (Hct), and platelet counts for all of our adult patients who underwent RBCX transfusions on both instruments.Methods:This was a single institution, retrospective chart review of all adult patients with sickle cell disease (HbSS n=17, HbS/β0 thalassemia n = 1, HbSC n =1) who underwent routine, monthly RBCX at Children's Hospital and Research Center Oakland between November 2013 and February 2015. Indications for RBCX included a risk of stroke or a history of stroke, acute chest syndrome, or renal failure. All patients received RBCX transfusions on the COBE Spectra prior to May 2014 and were then transitioned to Spectra Optia in May 2014. Pre and post-exchange transfusion HbS levels, WBC, Hct, and platelet counts were measured for each procedure. All exchange transfusions were non-emergent and well tolerated. Statistical analyses using the student's t test and rank sum test were performed with Stata 14.0 software (College Station, Texas).Results:A total of 19 adult patients (mean average age 25 years old) underwent 153 red blood cell exchange transfusions (Spectra Optia n =87, COBE Spectra n = 66). There was a small increase in mean hematocrit percentage for both instruments (28.33 + 4.3 % to 29 + 3.06 % and 28.16 + 4.29% to 29.2 + 3.04% on the Spectra Optia and COBE Spectra, respectively). All other post-RBCX parameters decreased. The mean changes are shown in Table I. The HbS percent decreased from a combined mean of 39.86 + 12.11 % to 20.26 + 8.43 % for both instruments. The WBC decreased from a combined mean of 12.72 + 3.13 x 1000/ mm3 to 8.67 + 2.15 x 1000/ mm3. The platelet count decreased from a combined mean of 368.82 + 125.75 x 1000/ mm3 to 191.01 + 62.78 x 1000/ mm3. The mean parameter values for each patient correlated with the mean changes for each instrument based on statistical analysis using both the student's t test and rank sum test.Conclusions:The starting hematologic values were similar between the two instruments. There was no statistical difference between the raw pre and post-RBCX HbS, Hct, WBC, or platelet values or the mean changes in these parameters between the COBE Spectra and Spectra Optia instruments. There was also no statistical difference in the mean changes between the pre and post RBCX hematologic parameters amongst the 19 patients. Both instruments allowed for effective reduction in HbS percentage with comparable decreases in WBC and platelet counts while maintaining adequate hematocrit values for all 19 adult patients with sickle cell disease.Table 1Mean changes between Pre-RBCX and Post-RBCX.InstrumentChange in % HbSChange in WBC x1000/mm3Change in % HctChange in platelet count x1000/mm3Spectra OptiaN84878785Mean-20.28-4.010.67-172.44SD7.022.552.8676.98COBE SpectraN66666666Mean-19.18-4.121.09-178.02SD7.892.262.5781.02p-value0.370.780.340.67There are 3 missing values for HbS and 2 missing values for platelet count for Spectra Optia. SD = standard deviation, WBC = white blood cell count, Hct = hematocrit DisclosuresNo relevant conflicts of interest to declare.

Should appendectomy be performed laparoscopically? Clinical prospective randomized trial.

Laparoscopic appendectomy (LA) has been described in 1983, and its superiority over open appendectomy (OA) is still being debated. Currently, there is no agreement on the advantages of LA. Postoperative pain is reported to be lower along with a faster return to normal activities in LA. However, some studies do not support these findings. In our study, we aimed to compare the outcomes and cost effectiveness of LA and OA. Patients were prospectively randomized into LA (31 patients) and OA (32 patients) groups. Demographic data, pre- and postoperative C-reactive protein (CRP) levels, white blood cell (WBC) count, duration of surgery and hospitalization, complications, and pain scores (VAS) were recorded. Cost was calculated for both groups. Return to normal activities was evaluated by phone calls at the first and second week and 1 month after surgery. There was a significant postoperative decrease in WBC count in the LA group (p<0.01). There were no differences between LA and OA groups in terms of postoperative CRP levels (p>0.05). The rates of wound infection and abscess were similar (p>0.05), while post-operative pain and time to return to normal activities were higher in the OA group (p<0.01). There was a positive correlation between BMI and operative time in the LA group (p<0.01), while BMI and operative time did not show a correlation in the OA group (p>0,05). The average cost in the LA and OA groups were 1960.5±339.05 and 687.115±159.5 TL, respectively. LA is an effective method in the treatment of acute appendicitis due to less pain and faster recovery. LA can be the choice of treatment in acute appendicitis, with utilization of re-useable and cheaper vascular sealing devices.

Determinants of Inter-Procedure Interval in Patients with Sickle Cell Anemia Enrolled a Chronic Red Blood Cell Exchange Program

Background:Sickle cell anemia (SCA) is a genetically inherited disorder that can lead to severe sequelae in any organ system. The most clinically devastating complications, e.g. stroke, are managed with chronic red blood cell (RBC) transfusions as curing the underlying SCA is often not an option. Chronic RBC exchange (RBCx), is an effective alternative to simple transfusions and often performed every 4-5 weeks. Isovolemic Hemodilution-Red Blood Cell Exchange (IHD-RBCx) is a modified RBCx method used at UT Southwestern Medical Center (UTSW) and increases the time interval between transfusions, i.e. inter-procedure interval (IPI), up to 9 weeks while maintaining the desired hemoglobin S targets at safe levels. This minimizes the overall lifetime procedures and blood exposures. The standard operating procedure for IHD-RBCx is published (Matevosyan et al, 2012). However, we observed IPI variability between patients in this chronic IHD-RBCx program. We sought to analyze hematologic characteristics in a cohort of adult SCA patients that may be associated with this noted variability.Methods:This IRB approved cross-sectional study evaluated medical and blood bank records of adult patients with SCA, i.e. hemoglobin SS or Sβ0 thalassemia genotypes, undergoing chronic IHD-RBCx at UTSW adult hospital sites between January 1, 2012 and December 31, 2013. Excluded participants were those with autoimmune disease, non-compliance with IHD-RBCx leading to delays > 7 days, or use of hydroxyurea or steroids within four months of the study period. Patients with < 5 exchanges were excluded as several procedures are needed to determine baseline IPIs. The primary indication for IHD-RBCx was secondary stroke prevention. Three subjects had alternative indications (i.e. recurrent severe acute chest syndrome that failed hydroxyurea therapy, intractable pain and severe anemia ineligible for iron chelation due to end-stage renal disease). Median values during the 2 year study were determined for the IPI, laboratory, and RBC properties for use in subsequent analyses. Correlation and multiple regression analyses were performed to determine variables predictive of IPI.Results:Twenty-four SCA patients in this chronic IHD-RBCx transfusion program met inclusion criteria of which 14 (58.3%) were female with age range 18-41 years. Three subjects had incomplete data. The median number of packed RBC (pRBC) units per IHD-RBCx was 8 (range: 6-11 units). The median volume per unit of pRBCs was 304.5 mL (range: 298.8-326.5 mL) with average age of the pRBCs 5.8 days ± 0.7 days. The median IPI was 55.8 days (range: 36.0-65.5 days).The strongest correlation with IPI was the change from the mid to post-procedure hemoglobin and hematocrit values, r=0.56, p=0.005 and r=0.57, p=0.003, respectively. Participants with documented direct antiglobulin test positivity (n=7), compared to those who remained negative (n=16), had 4.9 days increased IPI. This difference was not statistically significant, p=0.19. ABO differences in blood type also did not show statistical significant differences. However, A+ subjects had a 58 day interval compared to 51, 52, 53 days for B+, O+, O- respectively (Figure). In multiple regression models, log blood urea nitrogen (BUN) and post-procedure white blood cell count (WBC) were found to be independent predictors of IPI, beta=-11.3, p=0.04 and -2.1, p=0.03 respectively, with adjusted R2=0.31.Conclusions:Chronic IHD-RBCx effectively treats severe SCA complications. Discontinuing transfusions lead to repeat stroke events or the recurrence of disease manifestations making chronic transfusion programs an indefinite therapy. Outside of the expected correlation between the IPI and hemoglobin/hematocrit, WBC and BUN were found to have negative associations with IPIs. The decrease in WBCs is likely due to the direct clearing effect by the operating system. The association between BUN and IPI may imply relationship with renal function. Interestingly, association with creatinine was not statistically significant. The study is limited by the small sample size. Future studies of similar cohorts should prospectively evaluate target mechanisms which may lead to interventions that can minimize lifetime blood exposures given the growing demands for continued RBCx in severe SCA. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Phase Ii Study of Carboplatin/Etoposide Plus Ly2510924, a Cxcr4 Peptide Antagonist, Versus Carboplatin/Etoposide in Patients with Extensive-Stage Small Cell Lung Cancer (Sclc)

ABSTRACT Aim: LY2510924, an antagonist to the chemokine receptor CXCR4, inhibits tumor growth and metastasis in xenograft models. A Phase I trial with LY2510924 demonstrated an acceptable safety profile with a robust pharmacodynamic profile. This open-label phase II trial evaluated the clinical benefit of carboplatin/etoposide plus LY2510924 versus carboplatin/etoposide, the standard of care (SOC), as a first-line therapy in patients (pts) with extensive-stage SCLC. Methods: Treatment-naive extensive-stage SCLC pts were randomized 1:1 to receive six 21-day cycles of either LY+SOC (Arm A) or SOC (Arm B). A 20-mg dose of LY2510924 was self-administered by the patient subcutaneously on days 1-7 of each cycle. Efficacy was evaluated using RECIST v. 1.1; adverse events were evaluated using MedDRA v. 14.0. The primary end point, progression-free survival (PFS), was analyzed using a stratified log-rank test. Secondary end points were objective response rate (ORR), duration of overall response (DoR), overall survival (OS), and safety. Results: Median follow-up time was 8.4 months. Pt characteristics were comparable in Arm A (N=47) and Arm B (N=43). Median PFS for Arm A was 5.88 months (95% confidence interval 4.83, 6.24) and Arm B 5.85 months (4.63, 6.51), p=0.9806. ORRs were 74.5% and 81.0%; median DoR were 4.83 months (3.58, 5.09) and 4.67 months (3.32, 5.78) for Arms A and B, respectively. The median OS was 9.72 months (6.64, 11.70) and 11.14 months (8.25, 13.44), p=0.1120 for Arms A and B, respectively. Grade 3/4 treatment-emergent adverse events>8% in Arm A included neutrophil count decrease (40% vs. 56%), anemia (30% vs. 33%), platelet count decrease (23% vs. 16%), lung infection (11% vs. 0%), white blood cell count decrease (9% vs. 9%), and febrile neutropenia (9% vs. 2%) (Arm A vs. Arm B). No pts died due to adverse events. Conclusions: No improvements in PFS, ORR, DoR, or OS in treatment-naive extensive-stage SCLC pts were observed when LY2510924 was added to SOC. The addition of LY2510924 to SOC appeared to increase incidence of lung infection and febrile neutropenia; otherwise, the overall toxicity profile was acceptable in this patient population. Disclosure: O. Hamid: Oday Hamid is employed by Eli Lilly, the sponsor of the study and owns stock in the company; J.R. Stille: Employee of Eli Lilly and Company; J. Polzer: Employee of Eli Lilly and Company. S. Roberson: Employee of Eli Lilly and Company. All other authors have declared no conflicts of interest.

Clinical Study on the Relationship Between Hematocytopenia and Splenomegaly Caused by Cirrhotic Portal Hypertension

This clinical study was designed to evaluate the presence of hematocytopenia in patients with splenomegaly caused by non-alcoholic cirrhotic portal hypertension. For this purpose, we randomly selected 358 patients with splenomegaly caused by non-alcoholic cirrhotic portal hypertension and admitted to the clinical data in our hospital between January 1991 and June 2009. Among these 358 patients, 322 patients (90.0 %) showed hematocytopenia, including multi-hemocyte decrease in 206 patients (i.e., 89 patients with a decrease in white blood cell count (WBC) + red blood cell count (RBC) + platelets count (PLT)); 52 patients with WBC + PLT decrease; 29 patients with RBC + PLT decrease; and 36 patients with WBC + RBC decrease) and single-hemocyte decrease in 116 patients (i.e., 31 cases with single PLT decrease; 29 cases with single WBC decrease; and 56 patients with single RBC decrease). After splenectomy, 36 patients (10.0 %) with hematocytopenia presented a statistical improvement of blood cell to normal level (P < 0.05), while 32 patients did not have any change as compared to pre-operative one (P > 0.05). It has to be noted that 4 patients did not received any surgery. Hematocytopenia was not detected in all the patients with splenomegaly caused by cirrhotic portal hypertension, thus it is probably a complication of splenomegaly but not an inevitable manifestation. It was concluded that splenectomy could be an effective treatment for splenomegaly associated with hematocytopenia, but patients without hematocytopenia could choose a non-surgical alternative treatment.

Methisoprinol for children with early phase dengue infection: a pilot study

Background Dengue fever is associated with many healthcomplications and medical costs. Furthermore, there is currentlyno approved dengue antiviral medication or vaccine. Empiricevidence has suggested that patients who received supplementalmethisoprinol therapy had faster recovery times and fewercomplications .Objective To detennine the effects of oral methisoprinol on theclinical course and laboratory findings of children with early phasedengue infection.Methods We conducted a randomized, double-blind study fromJune to September 2012 on 22 children aged 2.7-16.8 years withlaboratory-confirmed early dengue infection. Subjects had notpreviously received antithrombotic agents, nor did they havebleeding disorders or immunodeficiency. We randomized thesubjects to receive either oral methisoprinol (100 mg/kg BW/day,divided into four doses) or placebo for 72 hours, with 11 subjectsper group. The primary endpoint was fever clearance time (FCT),and secondary endpoints were platelet nadii; white blood cell(WBC) nadii; maximum hemoconcentration, length of hospitalstay, and development of complications .Results The mean decrease in WBC count was less withmethisoprinol than with placebo [1.14 (SD 0.84) vs 2.60 (SD 3.12)x [09 /L; P = 0.004]. In addition, the mean decrease in platelet countwas less in patients on methisoprinol [38.36 (SD 58.3) vs. 50.46 (SD73.42) x 109/L; P=0.046]. No significant differences between thetwo groups were found for FCT (P=0.158), length ofhospital stay(P=0.511), hemoconcentration, or dengue complications.Conclusion Methisoprinol initiated at an early phase in dengueinfection reduced the anticipated leukopenia by 56% andthrombocytopenia by 24%. Hence it can be used along withstandard approved fluid and antipyretic therapy.

Decrease in white blood cell counts after thiopentone barbiturate therapy for refractory intracranial hypertension: A common complication

Background:Leucopenia has been reported after induction of thiopentone barbiturate therapy for refractory intracranial hypertension. However, the incidence and characterisitics are not well described.Aims:We performed a retrospective review to describe the incidence and characteristics of leucopenia after induction of thiopentone barbiturate therapy.Setting and Design:Our centre is a national referral centre for neurotrauma and surgery in a tertiary medical institution.Materials and Methods:We performed a retrospective review of all patients who received thiopentone barbiturate therapy for refractory intracranial hypertension during an 18 month period from January 2004 to June 2005 in our neurosurgical intensive care unit.Statistical Analysis Used:Statistical analysis was performed using SPSS version 15.0. All data are reported as mean ± standard deviation or median (interquartile range). The Chi square test was used to analyze categorical data and student t test done for comparison of means. For paired data, the paired t-test was used.Results:Thirty eight (80.9%) out of 47 patients developed a decrease in white blood cell (WBC) count after induction of thiopentone barbiturate coma. The mean decrease in WBC from baseline to the nadir was 6.4 × 109/L (P < 0.001) and occurred 57 (3-147) h after induction. The mean nadir WBC was 8.6 ± 3.6 × 109/L. Three (6.4%) patients were leucopenic, with a WBC count of 2.8, 3.1, and 3.6 × 109/L. None of them were neutropenic. We did not find an association between decrease in WBC count and clinical diagnosis of infection. We did not find any association between possible risk factors such as admission GCS, maximum ICP prior to induction of barbiturate coma, APACHE II score, total duration and dose of thiopentone given, and decrease in WBC count.Conclusions:Decrease in WBC count is common, while development of leucopenia is rare after thiopentone barbiturate coma. Regular monitoring of WBC counts is recommended.

Dietary Determinants Of The White Blood Cell Count

IntroductionWhite blood cells are key components of the immune system. They defend the body against a host of diseases and infections. Various studies have explored the possible influence of dietary nutrients on the white blood cell (WBC) count. If it can be demonstrated that nutrients affect the WBC count, they may offer an inexpensive way of modulating the immune system and in turn, the body's ability to fight against disease and infection. The sample sizes of previous studies, however, have been relatively small. The results have therefore been variable and conflicting. The purpose of this study is to continue to explore the dietary determinants of the WBC count, using a database that allows for a larger sample size, the 2005-2006 National Health and Nutrition Health Survey (NHANES). MethodsThe main outcome variable, WBC count, was recoded to the normal range for ages ≥ 18 years, of 4-11(±2). This was done in order to account for extreme values; particularly high and low values secondary to disease or infection. The population means and 95% confidence intervals were obtained using the statistical weights for the key variables of interest (Table 1). Multiple linear regression and backward elimination were used to predict the final model (Table 2). Variables with p < 0.1 were kept in the model. SAS 9.3 was used for all statistical analyses. ResultsAssociations for age, gender, race and Body Mass Index (BMI) and WBC count, were consistent with previous studies and were all statistically significant (p< 0.0001). It has been shown that more intense physical activity usually leads to an increase in the WBC count. In this study, however, more vigorous forms of activity were associated with a lower WBC count (p < 0.0001). Increases in dietary copper and iron were associated with a subsequent decrease in the WBC count (Table 2, p < 0.05). An increase in vitamin K was also associated with a decrease in WBC count, however, it was not statistically significant (Table 2, p > 0.05). Increases in vitamin B1 were associated with an increase in WBC count (p < 0.05). ConclusionThe results of this study suggest that further prospective studies are needed to investigate the role of these nutrients as determinants of the WBC count. Disclosures:No relevant conflicts of interest to declare.

The impact of co-infections on the haematological profile of East African Short-horn Zebu calves.

The cumulative effect of co-infections between pathogen pairs on the haematological response of East African Short-horn Zebu calves is described. Using a longitudinal study design a stratified clustered random sample of newborn calves were recruited into the Infectious Diseases of East African Livestock (IDEAL) study and monitored at 5-weekly intervals until 51 weeks of age. At each visit samples were collected and analysed to determine the infection status of each calf as well as their haematological response. The haematological parameters investigated included packed cell volume (PCV), white blood cell count (WBC) and platelet count (Plt). The pathogens of interest included tick-borne protozoa and rickettsias, trypanosomes and intestinal parasites. Generalized additive mixed-effect models were used to model the infectious status of pathogens against each haematological parameter, including significant interactions between pathogens. These models were further used to predict the cumulative effect of co-infecting pathogen pairs on each haematological parameter. The most significant decrease in PCV was found with co-infections of trypanosomes and strongyles. Strongyle infections also resulted in a significant decrease in WBC at a high infectious load. Trypanosomes were the major cause of thrombocytopenia. Platelet counts were also affected by interactions between tick-borne pathogens. Interactions between concomitant pathogens were found to complicate the prognosis and clinical presentation of infected calves and should be taken into consideration in any study that investigates disease under field conditions.