Abnormal White Blood Cell Research Articles

Fever, Abnormal White Blood Cell Count, Neutrophilia, and Elevated Serum C-Reactive Protein in Adult Hospitalized Patients with Bacteremia

Relatively little is known about the prevalence of and factors associated with the absence of fever, normal white blood cell count (WBC), lack of neutrophilia, and the frequency of elevated serum C-reactive protein (CRP) in adult hospitalized patients with bacteremia. Frequencies of fever (temperature ≥ 100°F), abnormal WBC count (≥ 10,000/μL or <4500/μL), neutrophilia (neutrophils ≥ 80%) and potential factors that may be associated with negative results, and frequency of elevated serum CRP were studied retrospectively in 622 bacteremic episodes in adult patients at a community teaching hospital. The frequencies of individual parameters were as follows: fever, 78.4% (95% confidence interval [CI] 74.9%-81.6%); abnormal WBC count, 65.2% (95% CI 61.3%-69.0%); neutrophilia, 67.5% (95% CI 63.7%-71.2%); and elevated CRP (>0.8 mg/dL), 98.4% (95% CI 97%-99.2%). Age 50 years and older, corticosteroid use, and isolation of either Staphylococcus sp not aureus or Enterococcus sp combined were independently associated with the absence of fever (P ≤ 0.01 for all). Isolation of Staphylococcus sp not aureus/Enterococcus and lack of corticosteroid use were independently associated with normal WBC (P < 0.05 for both). Nonwhite race and primary bacteremia were independently associated with lack of neutrophilia (P < 0.05 for both). Absence of fever, normal WBC, and lack of neutrophilia are common in patients with bacteremia and may be confounded by a variety of factors; however, serum CRP remains elevated in the majority (>98%) of bacteremic episodes.

When Is Death Inevitable after Emergency Laparotomy? Analysis of the American College of Surgeons National Surgical Quality Improvement Program Database

In an era of increasing demands to provide high-quality health care, surgeons need an accurate preoperative risk assessment tool to facilitate informed decision-making for themselves and their patients. Emergency laparotomy procedures have a high risk profile, but the currently available risk-assessment models for emergency laparotomy are either unreliable (eg, small sample size or single center study), difficult to calculate preoperatively, or are specific to the geriatric population. The American College of Surgeons National Surgical Quality Improvement Program database (2005 to 2009) was used to develop logistic regression models for 30-day mortality after emergency laparotomy. Two models were created, one with the knowledge of the postoperative diagnosis and one without. Models' calibration and discrimination were judged using the receiver operating characteristics curves and the Hosmer-Lemeshow test. There were 37,553 patients who had undergone emergency laparotomy, with a 14% mortality rate. The American Society of Anesthesiologists classification system, functional status, sepsis, and age were the variables most significantly associated with mortality. Patients older than 90 years of age, with an American Society of Anesthesiologists class V, septic shock, dependent functional status, and abnormal white blood cell count have a <10% probability of survival. The models developed in this study have a high discriminative ability to stratify the operative risk in a broad range of acute abdominal emergencies. These data will assist surgeons, patients, and their families in making end-of-life decisions in the face of medical futility with greater certainty when emergency surgery is being contemplated.

Risk factors of Clostridium difficile-associated diarrhea in children

To explore the risk factors of Clostridium difficile-associated diarrhea (CDAD) in children. From December 2010 to March 2011, the hospitalized diarrheal patients under 18 years old at Beijing Children's Hospital were tested for Clostridium difficile. The CDAD(+) patients were selected and their fecal specimens were PCR-positive for tcdA and (or) tcdB genes. And the patients with healthcare facility-associated-CDAD (HCFA-CDAD) were selected from the group of CDAD(+). The CDAD patients were selected and their fecal specimens were PCR-negative for tcdA and (or) tcdB genes. And the 1:3 matched controls per case were selected from those hospitalized patients without diarrhea at the same department with similar diseases during the same period. The potential predictors of CDAD included age, gender, co-morbidities, prior hospitalization, the administration of C. difficile-active antibiotics during prior 24 hours, recent (< 1 month) exposure to antibiotics or acid-blocking medications or nonsteroidal anti-inflammatory drug (NSAID), C-reactive protein (CRP) and white blood cell (WBC), etc. Multivariate Logistic regression models were created to identify the independent predictors of CDAD. Among 93 PCR tests, 35 were positive in fecal samples. There were HCFA-CDAD (n = 30) and CDAD(-) (n = 58). Thirty-five CDAD(+) hospitalized patients were compared with 105 controls. According to multivariate analyses, the predictors of CDAD included prior hospitalization (P < 0.01, OR = 0.002), CRP(P = 0.008, OR = 3.465), NSAID (P = 0.015, OR = 13.950) and WBC (P = 0.003, OR = 8.063). The administration of NSAID, elevated CRP and abnormal WBC are significantly associated with CDAD.

Prevalence of Healthcare-Associated Infections in Acute Care Hospitals in Jacksonville, Florida

To determine healthcare-associated infection (HAI) prevalence in 9 hospitals in Jacksonville, Florida; to evaluate the performance of proxy indicators for HAIs; and to refine methodology in preparation for a multistate survey. Point prevalence survey. Acute care inpatients of any age. HAIs were defined using National Healthcare Safety Network criteria. In each facility a trained primary team (PT) of infection prevention (IP) staff performed the survey on 1 day, reviewing records and collecting data on a random sample of inpatients. PTs assessed patients with one or more proxy indicators (abnormal white blood cell count, abnormal temperature, or antimicrobial therapy) for the presence of HAIs. An external IP expert team collected data from a subset of patient records reviewed by PTs to assess proxy indicator performance and PT data collection. Of 851 patients surveyed by PTs, 51 had one or more HAIs (6.0%; 95% confidence interval, 4.5%-7.7%). Surgical site infections ([Formula: see text]), urinary tract infections ([Formula: see text]), pneumonia ([Formula: see text]), and bloodstream infections ([Formula: see text]) accounted for 75.8% of 58 HAIs detected by PTs. Staphylococcus aureus was the most common pathogen, causing 9 HAIs (15.5%). Antimicrobial therapy was the most sensitive proxy indicator, identifying 95.5% of patients with HAIs. HAI prevalence in this pilot was similar to that reported in the 1970s by the Centers for Disease Control and Prevention's Study on the Efficacy of Nosocomial Infection Control. Antimicrobial therapy was a sensitive screening variable with which to identify those patients at higher risk for infection and reduce data collection burden. Additional work is needed on validation and feasibility to extend this methodology to a national scale.

Automated hematology analysers and spurious counts#$##x0000A;Part 2. Leukocyte count and differential

Using hematology analysers, white blood cell (WBC) counts and differentials (either three or five parameters) may be ascertained after Red Blood Cell (RBC) lysis and analysis using either impedance and/or optical (laser) technology. Cells or particles not destroyed by lytic agents are enumerated as WBC: abnormal particles may be observed on WBC differential scattergrams, if performed, appearing as a variable number of dots, which location may help to ascertain the nature of the abnormality. Spuriously low WBC counts are rare, mainly related to agglutination in the presence of ethylenediamine tetra-acetic acid. Cryoglobulins, lipids, insufficiently lysed RBC, erythroblasts and platelet aggregates are common situations increasing WBC counts. So far, many current high performance analysers clearly identify and enumerate erythroblasts now. In normal patients and in reactive disorders automated differential provides true and accurate results. However, failure to enumerate accurately basophilic granulocytes and monocytes is not uncommon. Using myeloperoxidase cytochemistry to ascertain differential may lead to slide review if the enzyme expression is low or absent. Low number of abnormal cells (blasts, lymphoma cells, dysplastic granulocytes) may be missed, more frequently if leukopenia is present. In many but not all instances flagging and/or an abnormal WBC differential scattergram will alert the operator. Although these flags are sensitive enough to allow the identification of several spurious counts, only the most sophisticated analysers have optimal flagging, whereas more simple ones, especially those without a WBC differential scattergram, do not demonstrate the same sensitivity for the detection of abnormal results.

Viral-Associated Trichodysplasia

Viral-associated trichodysplasia of immunosuppression is a rare cutaneous eruption that is characterized by follicularly based shiny papules and alopecia with characteristic histopathologic findings of abnormally anagen follicules with excessive inner root sheath differentiation. Prior reports have described the histopathologic characteristics on vertical sections; however, to our knowledge, immunohistochemical analysis of polyomavirus proteins has not been previously performed. We discuss the thorough diagnostic evaluation and therapy of an unusual case of viral-associated trichodysplasia due to a newly described human polyomavirus that occurred in a patient with posttreatment chronic lymphocytic leukemia and an abnormal white blood cell count. Unique to our study is the immunohistochemical staining for the polyomavirus middle T antigen, which demonstrated positive staining of cellular inclusions within keratinocytes that compose the inner root sheath. Further evaluation with scanning electron microscopy and polymerase chain reaction analysis of viral DNA confirmed the presence of the virus. Treatment with topical cidofovir resulted in dramatic clinical improvement and hair regrowth. Several tools, including immunohistochemical staining for the polyomavirus middle T antigen, can be used to identify the pathogenic virus associated with viral-associated trichodysplasia. This case highlights the utility of multiple diagnostic modalities and a robust response to a topical therapeutic agent, cidofovir.

Isolation and two-step classification of normal white blood cells in peripheral blood smears

Introduction: An automated system for differential white blood cell (WBC) counting based on morphology can make manual differential leukocyte counts faster and less tedious for pathologists and laboratory professionals. We present an automated system for isolation and classification of WBCs in manually prepared, Wright stained, peripheral blood smears from whole slide images (WSI). Methods: A simple, classification scheme using color information and morphology is proposed. The performance of the algorithm was evaluated by comparing our proposed method with a hematopathologist's visual classification.The isolation algorithm was applied to 1938 subimages of WBCs, 1804 of them were accurately isolated. Then, as the first step of a two-step classification process, WBCs were broadly classified into cells with segmented nuclei and cells with nonsegmented nuclei. The nucleus shape is one of the key factors in deciding how to classify WBCs. Ambiguities associated with connected nuclear lobes are resolved by detecting maximum curvature points and partitioning them using geometric rules. The second step is to define a set of features using the information from the cytoplasm and nuclear regions to classify WBCs using linear discriminant analysis. This two-step classification approach stratifies normal WBC types accurately from a whole slide image. Results: System evaluation is performed using a 10-fold cross-validation technique. Confusion matrix of the classifier is presented to evaluate the accuracy for each type of WBC detection. Experiments show that the two-step classification implemented achieves a 93.9% overall accuracy in the five subtype classification. Conclusion: Our methodology achieves a semiautomated system for the detection and classification of normal WBCs from scanned WSI. Further studies will be focused on detecting and segmenting abnormal WBCs, comparison of 20× and 40× data, and expanding the applications for bone marrow aspirates.

Pilot study on developing a decision support tool for guiding re-administration of chemotherapeutic agent after a serious adverse drug reaction

BackgroundCurrently, there are no standard guidelines for recommending re-administration of a chemotherapeutic drug to a patient after a serious adverse drug reaction (ADR) incident. The decision on whether to rechallenge the patient is based on the experience of the clinician and is highly subjective. Thus the aim of this study is to develop a decision support tool to assist clinicians in this decision making process.MethodsThe inclusion criteria for patients in this study are: (1) had chemotherapy at National Cancer Centre Singapore between 2004 to 2009, (2) suffered from serious ADRs, and (3) were rechallenged. A total of 46 patients fulfilled the inclusion criteria. A genetic algorithm attribute selection method was used to identify clinical predictors for patients' rechallenge status. A Naïve Bayes model was then developed using 35 patients and externally validated using 11 patients.ResultsEight patient attributes (age, chemotherapeutic drug, albumin level, red blood cell level, platelet level, abnormal white blood cell level, abnormal alkaline phosphatase level and abnormal alanine aminotransferase level) were identified as clinical predictors for rechallenge status of patients. The Naïve Bayes model had an AUC of 0.767 and was found to be useful for assisting clinical decision making after clinicians had identified a group of patients for rechallenge. A platform independent version and an online version of the model is available to facilitate independent validation of the model.ConclusionDue to the limited size of the validation set, a more extensive validation of the model is necessary before it can be adopted for routine clinical use. Once validated, the model can be used to assist clinicians in deciding whether to rechallenge patients by determining if their initial assessment of rechallenge status of patients is accurate.

Prognostic factors of Chinese patients with T/NK-cell lymphoma: a single institution study of 170 patients

T/natural killer-cell lymphoma (T/NKCL) is a heterogeneous group of lymphoma and has a higher incidence in Asia than in Western countries. T/NKCL is presented with various clinicopathologic features, and in general, associated with a poor clinical outcome. This study aims to analyze the clinical prognostic factors in patients with T/NKCL. From January 1999 to December 2009, a total of 170 patients with T/NKCL, except mycosis fungoides, were included in this retrospective study. The diagnosis was established according to World Health Organization classification. The clinical characteristics and prognostic factors were evaluated. Of the 170 patients, mainly peripheral T-cell lymphoma-unspecified (65 cases), precursor T-lymphoblastic lymphoma/leukemia (31 cases) and nasal NK/T-cell lymphoma (NKTCL, 19 cases), advanced disease (Ann Arbor stages III-IV) was presented in 68.8% and extranodal involvement was in 71.2% of the patients. According to the international prognostic index (IPI), 77 cases were categorized as high/intermediate or high-risk group. Using the prognostic index for peripheral T-cell lymphoma-unspecified (PIT), 87 cases were classified as group 3 or 4. Most of the initial regimens were CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone)-based chemotherapy (87.6%). Cumulative probability of overall survival at 5 years was 43%, and the median survival time was 44.5 months. Univariate analysis revealed that factors associated with a poor outcome were poor performance status (ECOG > 1) (P = 0.001), advanced disease (P = 0.009), the presence of B symptom (P = 0.001), multiple extranodal involvement (P = 0.005), bone marrow involvement (P = 0.003), elevated lactic dehydrogenase level (P = 0.019), IPI (P < 0.001), PIT (P < 0.001), abnormal white blood cell count (P = 0.016), decreased platelet count (P = 0.005) and serum Epstein-Barr virus (EBV) IgA positivity (P = 0.016). In the multivariate analysis, PIT (P < 0.001; relative risk, 3.221; 95% CI = 2.115-4.907) and EBV serum IgA (P = 0.049; relative risk, 1.901; 95% CI = 1.002-3.606) remained independent factors predictive for overall survival. The PIT may therefore be a useful index for risk stratification in patients with T/NKCL. The serum EBV antibody test could be a simple and quick marker to predict the outcome of the patients.

The identification of risk factors for critically ill patients with acute fever and formulation of activation criteria to alert outpatient clinic doctors

Acute fever is the most common early clinical symptom of many critical illnesses with a high mortality rate. It is necessary to identify patients with severe acute fever early and accurately. The aim of this study is to identify risk factors for critically ill outpatients with acute fever and formulate activation criteria of adult fever state score (AFSS) to alert outpatient clinic doctors. Retrospectively, 357 adult patients with acute fever were divided into two groups: 180 patients with a severe state and 177 patients with a mild state. Logistic regression was used to determine risk factors for the severe state. Risk factors were weighted and an AFSS was formulated. A receiver operating characteristic (ROC) analysis of weighted cumulative scores was performed to evaluate the diagnostic accuracy of AFSS, and the kappa test was used to confirm diagnostic reliability. A χ(2) -test for trend was applied to determine the relevance between AFSS and admission rate and in-hospital mortality. A Kruskal-Wallis test was used to examine the relationship between AFSS and length of stay. Risk factors for state included: old age, long fever course, past medical history, abnormal temperature, abnormal respiratory rate, abnormal heart rate, abnormal mean arterial pressure and abnormal peripheral white blood cell count. The area under the ROC curve of AFSS was 0.964 and ≥8 points predicted severe state; the Kappa value was 0.801. With an increase in score, there was an increase in admission rate, mortality rate and length of stay. The forecast performance of AFSS was superior to the modified early warning score. The AFSS has high diagnostic accuracy and reliability for the early identification of patients with severe acute fever.

Elevated red cell distribution width predicts poor outcome in young patients with community acquired pneumonia

IntroductionCommunity acquired pneumonia (CAP) is a major cause of morbidity and mortality. While there is much data about risk factors for severe outcome in the general population, there is less focus on younger group of patients. Therefore, we aimed to detect simple prognostic factors for severe morbidity and mortality in young patients with CAP.MethodsPatients of 60 years old or younger, who were diagnosed with CAP (defined as pneumonia identified 48 hours or less from hospitalization) between March 1, 2005 and December 31, 2008 were retrospectively analyzed for risk factors for complicated hospitalization and 90-day mortality.ResultsThe cohort included 637 patients. 90-day mortality rate was 6.6% and the median length of stay was 5 days. In univariate analysis, male patients and those with co-morbid conditions tended to have complicated disease. In multivariate analysis, variables associated with complicated hospitalization included post chest radiation state, prior neurologic damage, blood urea nitrogen (BUN) > 10.7 mmol/L and red cell distribution width (RDW) > 14.5%; whereas, variables associated with an increased risk of 90-day mortality included age ≥ 51 years, prior neurologic damage, immunosuppression, and the combination of abnormal white blood cells (WBC) and elevated RDW. Complicated hospitalization and mortality rate were significantly higher among patients with increased RDW regardless of the white blood cell count. Elevated RDW was associated with a significant increase in complicated hospitalization and 90-day mortality rates irrespective to hemoglobin levels.ConclusionsIn young patients with CAP, elevated RDW levels are associated with significantly higher rates of mortality and severe morbidity. RDW as a prognostic marker was unrelated with hemoglobin levels.Trial registrationClinicalTrials.Gov NCT00845312

Imatinib Treated Chronic Myelogenous Leukemia Concomitant with Multiple Myeloma. Is There a Relationship?

AbstractAbstract 5005Chronic myelogenous leukemia (CML) and multiple myeloma (MM) are hematological neoplasms with involvement of distinct hematopoietic cell lineages. The simultaneous occurrence of CML and MM is an extremely rare event. We report the case of a 46-year-old asymptomatic patient who was diagnosed with CML after an abnormal white blood cell count (90×109 u/L) was found on a routine complete blood cell count. Physical examination showed only splenomegaly. At diagnosis, a monoclonal protein peak was observed on electrophoresis (0.82g/dL). Bone marrow (BM) biopsy was characterized by granulocyte hyperplasia without clonal plasmacytosis. Karyotype showed t(9;22)(q34.1;q11.2) and a BCR/ABL mRNA transcript was detected by RT-PCR. Cytoreduction was initiated with hydroxyurea for 20 days until imatinib 400 mg/day was initiated. Patient achieved a major molecular response (MMR) after 7 months of treatment and remains in MMR. After 12 months from diagnosis, the patient persisted with monoclonal peak, and a new BM biopsy showed 15% monoclonal plasma cells, compatible with IgG lambda Myeloma. No end-organ damage was found, and there was no indication for therapy. Karyotype was 46, XX and a FISH analysis was positive for IgH rearrangement and for del 13q. At the time of this report the patient persists in MMR for CML with a monoclonal peak of 1.2 g/dL. No evidence of MM progression has been observed. These findings indicate coexistence of CML in chronic phase and monoclonal gamopathy of uncertain significance (MGUS), progressing to smoldering MM IgG lambda during IM treatment. At this moment, the association of CML and MM has been considered coincidental, but it is possible that imatinib may induce changes in phenotype of plasma cells which might lead to progression of multiple myeloma. Disclosures:No relevant conflicts of interest to declare.

Enhanced Antitumoral Activity of Sorafenib or Cetuximab In Comparison to Etoposide In a Disseminated Human AML Model In Vivo

AbstractAbstract 2141Acute myeloid leukemia (AML), one of the most common leukemia in adults, is characterized by the accumulation of abnormal white blood cells in the bone marrow. Even with modern advances in therapeutics and molecular diagnostics, the majority of AML patients die from their disease. Angiogenesis contributes to the development of hematologic malignancies, although its role has not been as clearly defined in hematologic malignancies as in solid tumors. In the present study we have determined antitumoral activity of two well-known inhibitors of angiogenesis. Sorafenib, a small molecule inhibitor affecting inter alia the VEGF pathway (100mg/kg/day (d); applied 12 consecutive days) and Cetuximab, a chimeric antibody against human EGFR (30 mg/kg/d; applied once weekly for 3 weeks) were evaluated in comparison to Etoposide, a topoisomerase II inhibitor (24mg/kg/day; applied 3 consecutive days) as a well established compound in AML treatment regimens in comparison with a control group. Equal parts of HL-60 cells were injected intravenously and into the peritoneal cavity of NOD/SCID mice and respective therapies were started 14 days after implantation. Tumor growth was monitored by a) daily monitoring of AML symptoms, and b) weekly fluorescence-based in vivo imaging (FI) using a Alexa750-labeled anti-human CD45 antibody and c) verification of the FI data by histological examination of bone marrow and spleen at the end of the study. Tumor inhibition was calculated as the proportional reduction of mean AML cell infiltration at the respective compartment of the test- compared to the control-group (in %). HL-60 cells engrafted predominantly in bone marrow (BM; take rate = 100%), but were as well detectable in the spleen (30%). At the respective doses and schedules the examined compounds were well tolerated in tumor-bearing mice. No acute toxicity could be observed and maximal body weight loss was below 15%. Tumor development was clearly reduced by Cetuximab (reduction of 53% vs control), albeit to a lesser extend then Sorafenib (reduction of 99% vs control), which induced a complete remission within the treatment period. Treatment of Etoposide induced no markable tumor growth inhibition (reduction of 10% vs control). Thus, HL-60 cells engrafted in NOD/SCID mice representing a valuable in vivo model for AML which exhibits high reproducibility and take-rates in relevant compartments closely mimicking the clinical situation. Collection of whole-body FI data proved to be a time- and animal-saving analysis that allows to closely monitor AML growth. With regard to the demographic development, AML will be more and more a disease of the elderly. Thus, development of new therapeutic options compared to high-dose chemotherapy will be highly required. As the VEGF and EGFR pathways are closely related, further investigations will include the evaluation of potentially synergistic effects in combination of Sorafenib with Cetuximab in human disseminated AML xenograft models. Disclosures:No relevant conflicts of interest to declare.

Factors predicting clinically significant fatigue in women following treatment for primary breast cancer

Cancer-related fatigue is common, complex, and distressing. It affects 70–100% of patients receiving chemotherapy and a significant number who have completed their treatments. We assessed a number of variables in women newly diagnosed with primary breast cancer (BrCa) to determine whether biological and/or functional measures are likely to be associated with the development of clinically significant fatigue (CSF). Two hundred twenty-three women participated in a study designed to document the impact of the diagnosis and treatment of primary breast cancer on function. Forty-four had complete data on all variables of interest at the time of confirmed diagnosis but prior to treatment (baseline) and ≥9 months post-diagnosis. Objective measures and descriptive variables included history, physical examination, limb volume, hemoglobin, white blood cell count, and glucose. Patient-reported outcomes included a verbal numerical rating of fatigue (0–10, a score of ≥4 was CSF), five subscales of the SF-36, Physical Activity Survey, and Sleep Questionnaire. At baseline, the entire cohort (n = 223) and the subset (n = 44) were not significantly different for demographic, biological, and self-reported data, except for younger age (p = 0.03) and ER+ (p = 0.01). Forty-five percent had body mass index (BMI) ≥ 25, 52% were post-menopause, and 52% received modified radical mastectomy, 39% lumpectomy, 52% chemotherapy, 68% radiation, and 86% hormonal therapy. Number of patients with CSF increased from 1 at baseline to 11 at ≥9 months of follow-up. CSF at ≥9 months significantly correlated with BMI ≥ 25, abnormal white blood cell count, and increase in limb volume and inversely correlated with vigorous activity and physical function (p < 0.05). Fatigue increases significantly following the treatment of BrCa. Predictors of CSF include high BMI and WBC count, increase in limb volume, and low level of physical activity. These are remediable.

Inadequacy of Temperature and White Blood Cell Count in Predicting Bacteremia in Patients with Suspected Infection

BackgroundEarly treatment of sepsis in Emergency Department (ED) patients has lead to improved outcomes, making early identification of the disease essential. The presence of systemic inflammatory response criteria aids in recognition of infection, although the reliability of these markers is variable. Study ObjectiveThis study aims to quantify the ability of abnormal temperature, white blood cell (WBC) count, and bandemia to identify bacteremia in ED patients with suspected infection. MethodsThis was a post hoc analysis of data collected for a prospective, observational, cohort study. Consecutive adult (age ≥ 18 years) patients who presented to the ED of a tertiary care center between February 1, 2000 and February 1, 2001 and had blood cultures obtained in the ED or within 3 h of admission were enrolled. Patients with bacteremia were identified and charts were reviewed for presence of normal temperature (36.1–38°C/97–100.4°F), normal WBC (4–12 K/μL), and presence of bandemia (> 5% of WBC differential). ResultsThere were 3563 patients enrolled; 289 patients (8.1%) had positive blood cultures. Among patients with positive blood cultures, 33% had a normal body temperature and 52% had a normal WBC count. Bandemia was present in 80% of culture-positive patients with a normal temperature and 79% of culture-positive patients with a normal WBC count. Fifty-two (17.4%) patients with positive blood cultures had neither an abnormal temperature nor an abnormal WBC. ConclusionA significant percentage of ED patients with blood culture-proven bacteremia have a normal temperature and WBC count upon presentation. Bandemia may be a useful clue for identifying occult bacteremia.

Interdigitating Dendritic Cell Sarcoma Involving Bone Marrow in a Liver Transplant Recipient

Liver transplantation is an effective treatment for patients with many kinds of liver diseases. However, an increased risk of de novo malignancy has been reported in liver transplant recipients; immunosuppressive drugs have generally been identified as the primary culprit. Interdigitating dendritic cell sarcoma (IDCS) is an exceedingly rare neoplasm arising from antigen-presenting cells of the immune system. In this study, we have reported a case of IDCS with bone marrow involvement occurring in a 61-year-old female liver transplant recipient at 2 years after the procedure. She was admitted to our center with fever, cough, and expectoration. Physical examination revealed firm and painless nodes in both cervical and axillary fossae. Routine examination revealed an abnormal white blood cell count and elevated serum lactate dehydrogenase. Computerized tomography of the chest, abdomen, and pelvis were negative. Viral infections were also excluded. To obtain a definite diagnosis, we performed an excisional lymph node biopsy and a bone marrow biopsy. Microscopically, the tumor was composed of spindle cells with pale to eosinophilic cytoplasm, ill-defined cell borders, and large pleomorphic nuclei with prominent nucleoli. Immunophenotypic analysis demonstrated positive staining for S-100, vimentin, CD163, and CD68. Follicular dendritic cell, lymphoid, epithelial, myoepithelial, and melanoma markers were negative. Histology revealed bone marrow involvement. Taken together, the above features were consistent with IDCS with bone marrow involvement. She responded to chemotherapy. This case demonstrates the importance of cancer prevention and early detection for liver transplant recipients.

Results of bone marrow examinations in patients with chronic immune thrombocytopenic purpura treated with eltrombopag

Abstract Abstract 1326 Poster Board I-348 BACKGROUND Bone marrow (BM) reticulin fibers can be increased in conditions such as neoplasms and autoimmune diseases (Frisch Haematol [Budap] 1982; Aharon Lupus 1997) and can lead to a clinical situation similar to osteomyelofibrosis. In healthy individuals, grade 1 and 2 reticulin have been reported in 27–70% and 4–20% of BM biopsies, respectively (Hultdin Med Onc 2007; Beckman Arch Path Int Med 1990; Bauermeister Am J Clin Path 1971). The presence of grade 1/2 reticulin was reported in the BM of up to 67% of patients with immune thrombocytopenic purpura (ITP) (Mufti J Supp Onc 2007). Theoretically, prolonged stimulation of megakaryocytes with TPO-R agonists might increase the risk of myelofibrosis (MF). Increased reticulin and peripheral nucleated RBCs have been reported in chronic ITP patients treated with romiplostim (Bussel Blood 2009). Eltrombopag, an oral, small molecule, TPO-R agonist, is approved in the United States for the treatment of chronic ITP. OBJECTIVE To determine whether eltrombopag treatment is associated with an increase in BM reticulin. METHODS Reports of BM biopsies performed prior to eltrombopag treatment were reviewed. In eltrombopag studies, complete blood counts (CBC) including white blood cell (WBC) differentials were performed at each visit. If a WBC differential indicated the presence of immature or dysplastic cells in the RAISE, REPEAT, and EXTEND studies, then a peripheral blood smear was performed. If the presence of immature or dysplastic cells on the blood smear was not consistent with the chronic ITP diagnosis, then a BM biopsy was performed. Additionally, a BM biopsy could be performed at any time at the investigator's discretion. In EXTEND, a BM biopsy was required after 1 year on treatment. Reticulin was quantified using the modified MF scale (Thiele Haematologica 2005). RESULTS Prestudy BM biopsies were available for 64/446 patients subsequently exposed to eltrombopag; 51 reports did not mention reticulin or fibrosis. Of the 13 remaining prestudy reports, 4 (31%) had increased reticulin. Ninety-one patients (5 patients RAISE; 86 patients EXTEND) had a BM biopsy following treatment initiation; none of the BM biopsies were prompted by an abnormal peripheral blood smear. In a 6-month placebo-controlled study (RAISE), 1 placebo-treated patient had an on-treatment BM examination that showed myelodysplastic syndrome, and 4 eltrombopag-treated patients (2 on-treatment and 2 posttreatment) had BM examinations. One patient treated with eltrombopag for 41 days had a posttreatment marrow examination that showed grade 2 (Bauermeister) reticulin. None of the 4 showed hematologically relevant BM alterations. In an open-label extension study (EXTEND), 86 patients treated for a median of 12 months (range: 1–18 months) at the time of the procedure had BM biopsies; 83 had mention of reticulin fibers in the report and were evaluable for this analysis. Five patients had MF grade 2 reticulin with no clinical signs or symptoms of BM dysfunction (eg, abnormal WBC differential or peripheral blood smear); 2 reported collagen. One patient had a biopsy 2 years prior to EXTEND (grade 1/3). After 15 months on study, a biopsy showed grade 2/3; this patient was withdrawn. Of note, while on treatment the patient was not considered a responder (platelets CONCLUSION There was no evidence of clinically relevant BM abnormalities or clinical findings typically associated with MF in patients treated for up to 18 months with eltrombopag. Systematic longitudinal evaluation of BMs in EXTEND will provide meaningful data regarding incidence of fibrosis during long-term treatment. Disclosures Saleh: GlaxoSmithKline: Speakers Bureau; Amgen: Speakers Bureau. Bussel: Genzyme: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai, Inc: Research Funding; Sysmex: Research Funding; Scienta: Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees. Meyer: GlaxoSmithKline: Consultancy, Honoraria. Frederiksen: GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees. Johnni: GlaxoSmithKline: Employment. Aivado: GlaxoSmithKline: Employment. Brainsky: GlaxoSmithKline: Employment.

Automated Detection of Malaria-Associated Pseudoeosinophilia and Abnormal WBC Scattergram by the Sysmex XE-2100 Hematology Analyzer: A Clinical Study with 1,801 Patients and Real-Time Quantitative PCR Analysis in Vivax Malaria-Endemic Area

Recently, the XE-2100 hematology analyzer was investigated in a rather small patient group; pseudoeosinophilia or abnormal white blood cell (WBC) scattergrams reported by this instrument were considered as significantly valuable diagnostic parameters in detecting vivax malaria. This study was conducted not only to assess the usefulness of pseudoeosinophilia or abnormal WBC scattergram in vivax malaria-endemic areas with large patient groups (N = 1,801) but also to investigate the correlation of parasitemia and platelet count with pseudoeosinophilia and abnormal WBC scattergrams. Of the 1,801 analyzed patients, 413 (22.9%) were found to have malaria by Wright-Giemsa stained blood smears. Overall, either pseudoeosinophilia or abnormal WBC scattergram was detected in 191 of 413 malaria patients and 4 of 1,388 patients without malaria (sensitivity = 46.2%, specificity = 99.7%). We suggest that clinical hematology laboratories using the XE-2100 analyzer should be aware of such specific parameters, even with the absence of a clinical request.

A Computerized Alert Screening For Severe Sepsis In Emergency Department Patients Increases Lactate Testing But Does Not Improve Inpatient Mortality

This study tested the hypothesis that lactate testing in ED sepsis patients could be increased using a computer alert that automatically recognizes systemic inflammatory response syndrome (SIRS) criteria and recommends lactate testing in cases of sepsis defined as ≥2 SIRS criteria plus physician suspicion of infection. Secondary outcomes included the effect of the alert on lactate testing among admitted sepsis patients, the proportion of admitted patients with lactate ≥4.0 mmol/L identified and the in-patient mortality difference before and after alert implementation. After a 6 month pre-alert phase, a computer alert was implemented that computed and displayed abnormal vital signs and white blood cell counts for all patients with >2 SIRS criteria and recommended testing lactate if an infection was suspected. Data for admitted patients was collected electronically on consecutive patients meeting sepsis criteria for 6 months before and 6 months after implementation of the alert. There were a total of 5,796 subjects enrolled. Among all septic patients, lactate testing increased from 5.2% in the pre-alert phase to 12.7% in the alert phase, a 7.5% (95% CI 6.0 to 9.0%) absolute increase in lactate testing, p<0.001. Among the 1,798 admitted patients with sepsis, lactate testing increased from 15.3% to 34.2%, an 18.9% (95% CI 15.0 to 22.8%) absolute increase, p<0.001. Among admitted patients with sepsis, there was a 1.9% (95% CI 0.03 to 3.8%, p = 0.05) increase in absolute number of patients with elevated lactate levels identified and a 0.5% (95% CI -1.6 to 2.6%, p=0.64) decrease in mortality. The proportion of ED patients who had lactate tested and the number of admitted patients identified with a lactate level ≥4.0 mmol/L improved significantly after the implementation of a computer alert identifying sepsis patients with >2 SIRS criteria while mortality among admitted sepsis patients remained unchanged.

Results of Bone Marrow Examinations in Patients with Chronic Immune Thrombocytopenic Purpura Treated with Eltrombopag.

Abstract 1326Poster Board I-348 BACKGROUNDBone marrow (BM) reticulin fibers can be increased in conditions such as neoplasms and autoimmune diseases (Frisch Haematol [Budap] 1982; Aharon Lupus 1997) and can lead to a clinical situation similar to osteomyelofibrosis. In healthy individuals, grade 1 and 2 reticulin have been reported in 27–70% and 4–20% of BM biopsies, respectively (Hultdin Med Onc 2007; Beckman Arch Path Int Med 1990; Bauermeister Am J Clin Path 1971). The presence of grade 1/2 reticulin was reported in the BM of up to 67% of patients with immune thrombocytopenic purpura (ITP) (Mufti J Supp Onc 2007). Theoretically, prolonged stimulation of megakaryocytes with TPO-R agonists might increase the risk of myelofibrosis (MF). Increased reticulin and peripheral nucleated RBCs have been reported in chronic ITP patients treated with romiplostim (Bussel Blood 2009). Eltrombopag, an oral, small molecule, TPO-R agonist, is approved in the United States for the treatment of chronic ITP. OBJECTIVETo determine whether eltrombopag treatment is associated with an increase in BM reticulin. METHODSReports of BM biopsies performed prior to eltrombopag treatment were reviewed. In eltrombopag studies, complete blood counts (CBC) including white blood cell (WBC) differentials were performed at each visit. If a WBC differential indicated the presence of immature or dysplastic cells in the RAISE, REPEAT, and EXTEND studies, then a peripheral blood smear was performed. If the presence of immature or dysplastic cells on the blood smear was not consistent with the chronic ITP diagnosis, then a BM biopsy was performed. Additionally, a BM biopsy could be performed at any time at the investigator's discretion. In EXTEND, a BM biopsy was required after 1 year on treatment. Reticulin was quantified using the modified MF scale (Thiele Haematologica 2005). RESULTSPrestudy BM biopsies were available for 64/446 patients subsequently exposed to eltrombopag; 51 reports did not mention reticulin or fibrosis. Of the 13 remaining prestudy reports, 4 (31%) had increased reticulin. Ninety-one patients (5 patients RAISE; 86 patients EXTEND) had a BM biopsy following treatment initiation; none of the BM biopsies were prompted by an abnormal peripheral blood smear. In a 6-month placebo-controlled study (RAISE), 1 placebo-treated patient had an on-treatment BM examination that showed myelodysplastic syndrome, and 4 eltrombopag-treated patients (2 on-treatment and 2 posttreatment) had BM examinations. One patient treated with eltrombopag for 41 days had a posttreatment marrow examination that showed grade 2 (Bauermeister) reticulin. None of the 4 showed hematologically relevant BM alterations. In an open-label extension study (EXTEND), 86 patients treated for a median of 12 months (range: 1–18 months) at the time of the procedure had BM biopsies; 83 had mention of reticulin fibers in the report and were evaluable for this analysis. Five patients had MF grade 2 reticulin with no clinical signs or symptoms of BM dysfunction (eg, abnormal WBC differential or peripheral blood smear); 2 reported collagen. One patient had a biopsy 2 years prior to EXTEND (grade 1/3). After 15 months on study, a biopsy showed grade 2/3; this patient was withdrawn. Of note, while on treatment the patient was not considered a responder (platelets <50,000/μL) but did have decreased bleeding. The second patient was 81 years old with a history of 3 cancers. A similar degree of reticulin was observed when comparing the biopsy taken 6 years prior to EXTEND and after 14 months on study, but collagen was noted on the second BM. A patient with MF grade 1 reticulin reported collagen, but did not experience any adverse event or significant change in CBC and is continuing on study with good platelet response. CONCLUSIONThere was no evidence of clinically relevant BM abnormalities or clinical findings typically associated with MF in patients treated for up to 18 months with eltrombopag. Systematic longitudinal evaluation of BMs in EXTEND will provide meaningful data regarding incidence of fibrosis during long-term treatment. DisclosuresSaleh:GlaxoSmithKline: Speakers Bureau; Amgen: Speakers Bureau. Bussel:Genzyme: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai, Inc: Research Funding; Sysmex: Research Funding; Scienta: Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees. Meyer:GlaxoSmithKline: Consultancy, Honoraria. Frederiksen:GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees. Johnni:GlaxoSmithKline: Employment. Aivado:GlaxoSmithKline: Employment. Brainsky:GlaxoSmithKline: Employment.