The ASH-ASPHO Choosing Wisely Campaign: 5 hematologic tests and treatments to question.

Choosing Wisely is a medical stewardship and quality-improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The American Society of Hematology (ASH) has been an active participant in the Choosing Wisely project. In 2019, ASH and the American Society of Pediatric Hematology/Oncology (ASPHO) formed a joint task force to solicit, evaluate, and select items for a pediatric-focused Choosing Wisely list. By using an iterative process and an evidence-based method, the ASH-ASPHO Task Force identified 5 hematologic tests and treatments that health care providers and patients should question because they are not supported by evidence, and/or they involve risks of medical and financial costs with low likelihood of benefit. The ASH-ASPHO Choosing Wisely recommendations are as follows: (1) avoid routine preoperative hemostatic testing in an otherwise healthy child with no previous personal or family history of bleeding, (2) avoid platelet transfusion in asymptomatic children with a platelet count >10 × 103/µL unless an invasive procedure is planned, (3) avoid thrombophilia testing in children with venous access-associated thrombosis and no positive family history, (4) avoid packed red blood cells transfusion for asymptomatic children with iron deficiency anemia and no active bleeding, and (5) avoid routine administration of granulocyte colony-stimulating factor for prophylaxis of children with asymptomatic autoimmune neutropenia and no history of recurrent or severe infections. We recommend that health care providers carefully consider the anticipated risks and benefits of these identified tests and treatments before performing them.

The ASH-ASPHO Choosing Wisely Campaign: 5 hematologic tests and treatments to question.

Choosing Wisely is a medical stewardship and quality-improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The American Society of Hematology (ASH) has been an active participant in the Choosing Wisely project. In 2019, ASH and the American Society of Pediatric Hematology/Oncology (ASPHO) formed a joint task force to solicit, evaluate, and select items for a pediatric-focused Choosing Wisely list. By using an iterative process and an evidence-based method, the ASH-ASPHO Task Force identified 5 hematologic tests and treatments that health care providers and patients should question because they are not supported by evidence, and/or they involve risks of medical and financial costs with low likelihood of benefit. The ASH-ASPHO Choosing Wisely recommendations are as follows: (1) avoid routine preoperative hemostatic testing in an otherwise healthy child with no previous personal or family history of bleeding, (2) avoid platelet transfusion in asymptomatic children with a platelet count 10 × 103 /µL unless an invasive procedure is planned, (3) avoid thrombophilia testing in children with venous access-associated thrombosis and no positive family history, (4) avoid packed red blood cells transfusion for asymptomatic children with iron deficiency anemia and no active bleeding, and (5) avoid routine administration of granulocyte colony-stimulating factor for prophylaxis of children with asymptomatic autoimmune neutropenia and no history of recurrent or severe infections. We recommend that health care providers carefully consider the anticipated risks and benefits of these identified tests and treatments before performing them.

Evaluation of a Sepsis Alert in the Pediatric Acute Care Setting.

BACKGROUND: Severe sepsis can cause significant morbidity and mortality in pediatric patients. Early recognition and treatment are vital to improving patient outcomes. OBJECTIVE: The study aimed to evaluate the impact of a best practice alert in improving recognition of sepsis and timely treatment to improve mortality in the pediatric acute care setting. METHODS: A multidisciplinary team adapted a sepsis alert from the emergency room setting to facilitate identification of sepsis in acute care pediatric inpatient areas. The sepsis alert included clinical decision support to aid in timely treatment, prompting the use of intravenous fluid boluses, and antibiotic administration. We compared sepsis-attributable mortality, time to fluid and antibiotic administration, proportion of patients who required transfer to a higher level of care, and antibiotic days for the year prior to the sepsis alert (2017) to the postimplementation phase (2019). RESULTS: We had 79 cases of severe sepsis in 2017 and 154 cases in 2019. Of these, we found an absolute reduction in both 3-day sepsis-attributable mortality (2.53 vs. 0%) and 30-day mortality (3.8 vs. 1.3%) when comparing the pre- and postintervention groups. Though our analysis was underpowered due to small sample size, we also identified reductions in median time to fluid and antibiotic administration, proportion of patients who were transferred to the intensive care unit, and no observable increase in antibiotic days. CONCLUSION: Electronic sepsis alerts may assist in improving recognition of sepsis and support timely antibiotic and fluid administration in pediatric acute care settings.

Iron Deficiency Is Associated with Adverse Outcomes in Pediatric Heart Failure.

OBJECTIVE: To evaluate the prevalence of iron deficiency and its association with outcomes in children with heart failure. STUDY DESIGN: A single-center retrospective cohort study of patients with heart failure aged 1-21 years from July 2012 to June 2017 with available serum iron studies was performed. Subjects were analyzed in 2 groups: biventricular systolic heart failure (BiV) and single-ventricle congenital heart disease with systolic heart failure (SV). Iron deficiency was defined as ≥2 of the following: serum iron <50 µg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, or transferrin saturation <15%. The primary outcome was a composite adverse event (CAE) of ventricular assist device implantation, heart transplantation, or death, at 3 and 6 months from time of iron studies. RESULTS: Of the 107 subjects (77 BiV, 30 SV) included in the study, 56% were iron deficient. Demographics, etiology of heart failure, and chronicity of heart failure symptoms were not associated with iron deficiency. On multivariable analysis, in group BiV, iron deficiency was associated with CAE at 3 months (79% iron deficiency in CAE group vs 37% iron deficiency in non-CAE, P = .001, OR 7, 95% CI 2-21) and 6 months (76% iron deficiency in CAE vs 35% iron deficiency in non-CAE, P = .002, OR 7, 95% CI 2-24). In group SV, iron deficiency was associated with CAE at 6 months (79% iron deficiency in CAE vs 29% iron deficiency in non-CAE, P = .014, OR 8, 95% CI 2-32). CONCLUSIONS: Iron deficiency was present in 56% of the pediatric patients with heart failure who were evaluated with iron studies. Iron deficiency was associated with greater risk of ventricular assist device implantation, heart transplantation, or death.

Work efficiency improvement of >90% after implementation of an annual inpatient blood products administration consent form.

Paediatric haematology, oncology and bone marrow transplant (BMT) patients frequently require transfusion of blood products. Our institution required a new transfusion consent be obtained every admission. The objectives of this project were to: revise inpatient blood products consent form to be valid for 1 year, decrease provider time spent consenting from 15 to <5 min per admission, and improve provider frustration with the consent process. Over 6 months, we determined the average number of hospitalisations requiring transfusions in a random sampling of haematology/oncology/BMT inpatients. We surveyed nurses and providers regarding frustration levels and contact required regarding consents. Four and 12 months after implementation of the annual consent, providers and nurses were resurveyed, and new inpatient cohorts were assessed. Comparison of preintervention and postintervention time data allowed calculation of provider time reduction, a surrogate measure of improved work efficiency. Prior to the annual consent, >33 hours were spent over 6 months obtaining consent on 40 patients, with >19 hours spent obtaining consent when no transfusions were administered during admission. Twelve months after annual consent implementation, 97.5% (39/40) of analysed patients had a completed annual blood products transfusion consent and provider work efficiency had improved by 94.6% (>30 hours). Although several surveyed variables improved following annual consent implementation, provider frustration with consent process remained 6 out of a max score of 10, the same level as prior to the intervention. Development of an annual inpatient blood products consent form decreased provider time from 15 to <1 min per admission, decreased consenting numbers and increased work efficiency by >90%.

Population Pharmacokinetics of Enoxaparin in Pediatric Patients.

BACKGROUND: There are no studies evaluating the pharmacokinetics of enoxaparin in the hospitalized pediatric patient population. OBJECTIVE: To characterize the pharmacokinetics of enoxaparin in pediatric patients. METHODS: A retrospective review of inpatients 1 to 18 years of age admitted to our institution who received enoxaparin with anti-factor Xa activity level monitoring was performed. Demographic variables, enoxaparin dosing, and anti-factor Xa activity levels were collected. Population pharmacokinetic analysis was performed with bootstrap analysis. Simulation (n = 10 000) was performed to determine the percentage who achieved targeted anti-Xa levels at various doses. RESULTS: A total of 853 patients (male 52.1%, median age = 12.2 years; interquartile range [IQR] = 4.6-15.8 years) received a mean enoxaparin dose of 0.86 ± 0.31 mg/kg/dose. A median of 3 (IQR = 1-5) anti-factor Xa levels were sampled at 4.4 ± 1.3 hours after a dose, with a mean anti-factor Xa level of 0.52 ± 0.23 U/mL. A 1-compartment model best fit the data, and significant covariates included allometrically scaled weight, serum creatinine, and hematocrit on clearance, and platelets on volume of distribution. Simulations were run for patients both without and with reduced kidney function (creatinine clearance of ≤30 mL/min/1.73 m2). A dose of 1 mg/kg/dose every 12 hours had the highest probability (72.3%) of achieving an anti-Xa level within the target range (0.5-1 U/mL), whereas a dose reduction of ~30% achieved the same result in patients with reduced kidney function. CONCLUSIONS: Pediatric patients should initially be dosed at 1-mg/kg/dose subcutaneously every 12 hours for treatment of thromboembolism followed by anti-Xa activity monitoring. Dose reductions of ~30% for creatinine clearance ≤30 mL/min/1.73 m2 are required.

Evaluation and Management of Acute-Onset Hemiparesis in an Adolescent With Leukemia.

Emergency departments (EDs) are alert to the possibility of stroke and the need for early interventions to improve long-term clinical outcomes. However, new-onset hemiparesis in pediatric patients with leukemia may be due to a number of different etiologies, including most common side effects from chemotherapeutic agents. We present a case of a 15-year-old boy with pre-B acute lymphoblastic leukemia on chemotherapy, having recently received a high-dose methotrexate infusion in addition to intrathecal methotrexate therapy, who presented to our ED with acute right-sided hemiparesis. He was initially suspected as having a possible ischemic stroke. Magnetic resonance imaging (diffusion-weighted and fluid-attenuated inversion recovery sequence) demonstrated focal areas of diffusion restriction, an early sign of delayed-onset methotrexate neurotoxicity. Our patient received appropriate supportive care and leucovorin rescue with gradual clinical recovery, after a prolonged hospitalization and acute care rehabilitation over the course of several months. Our case illustrates the need for ED providers to consider methotrexate neurotoxicity in pediatric oncology patients presenting with acute neurologic changes.

A Severe Case of Murine Typhus Presenting With Anemia and Severe Thrombocytopenia.

We discuss a child with severe thrombocytopenia and mild anemia admitted to the Hematology service who quickly deteriorated to a life-threatening state. However, once rickettsial disease was considered in the differential diagnosis and empiric doxycycline begun, she quickly and fully recovered. A diagnostic panel, including Rickettsia typhi serology, confirmed the diagnosis of murine typhus but this occurred weeks after she had recovered. Given the potential severity of rickettsial diseases and the ease of modern travel across geographic borders, hematology-oncology providers everywhere must consider rickettsial diseases in their differential diagnosis of critically ill children and begin empiric therapy with doxycycline promptly.

Prevalence of Anemia and Iron Deficiency in Pediatric Patients on Ventricular Assist Devices.

The prevalence and characteristics of anemia and iron deficiency in children supported by a ventricular assist device (VAD) are unknown. Patients <21 years of age on durable VAD support for ≥7 days at Texas Children's Hospital from 2006 to 2015 were retrospectively reviewed. Red blood cell (RBC) and iron deficiency indices in pulsatile VAD (P-VAD) and continuous-flow VAD (CF-VAD) were evaluated. Anemia, iron deficiency, and iron therapy regimens were identified. Seventy-six VAD implants in 74 patients were included: 45 P-VAD and 31 CF-VAD. Overall, 48% (36/75) of patients were anemic at VAD implant, with 67% of CF-VAD and 34% of P-VAD affected. Iron deficiency was seen in 52% (39/75) of patients at implant (similar in both groups). At explant, 71% (53/75) had anemia (similar in both groups). No patients had microcytosis. Iron supplementation was given to 20 patients, with four receiving target replacement therapy (2-6 mg/kg/d × 90 days). Red blood cell transfusion volumes were higher for P-VAD versus CF-VAD. We concluded that anemia and iron deficiency are common in pediatric VAD patients. Pulsatile VAD patients tend to develop anemia over the course of VAD support. Lack of microcytosis, likely masked by high RBC transfusions, suggests that specific iron studies are necessary to identify iron deficiency.

Enoxaparin Population Pharmacokinetics in the First Year of Life.

AIMS: Enoxaparin dosing requirements in the first year of life can be highly variable. Characterization of pharmacokinetics in this patient population can assist in dosing. METHODS: Patients less than 1 year postnatal age who received enoxaparin and had an anti-factor Xa activity level drawn as inpatients were identified through the pharmacy database over a 5-year period. Patients on renal replacement therapy or with hyperbilirubinemia were excluded. Data collection included demographic variables, indication for enoxaparin, enoxaparin doses, anti-factor Xa activity levels, serum creatinine, hemoglobin, hematocrit, platelet count, and urine output over the previous 24 hours. Population pharmacokinetic analysis was performed with NONMEM. RESULTS: A total of 182 patients [male 50%, median 100 days postnatal age (range: 4-353 days)] met the study criteria. Patients received median 22 doses (range: 1-526) at a mean starting dose of 1.38 ± 0.43 mg/kg with median 5 (range: 1-56) anti-factor Xa activity levels measured. A 1-compartment proportional and additive error model best fits the data. Allometrically scaled weight significantly decreased the objective function value, as did serum creatinine on clearance, and postmenstrual age (PMA) on volume of distribution. When evaluated graphically, dosing based on PMA appeared to have less variability as compared to postnatal age-based dosing. CONCLUSIONS: Dosing of enoxaparin in infants younger than 1 year should incorporate PMA.

Association of outcomes and anti-Xa levels in the treatment of pediatric venous thromboembolism.

BACKGROUND: There are few data in the pediatric population evaluating the relationship between measured anti-Xa levels during enoxaparin therapy and thrombotic outcomes. OBJECTIVE: To determine whether there is a difference in outcomes in children who receive enoxaparin with mean anti-Xa levels between 0.45 and 0.79 unit/ml (low therapeutic range) versus between 0.80 and 1.05 unit/ml (high therapeutic range) throughout their course of their treatment. METHODS: We retrospectively identified subjects with uncomplicated venous thromboembolism treated with enoxaparin. RESULTS: Of 69 patients with any response to therapy, 48 (70%) had mean anti-Xa levels in the low therapeutic range and 21 (30%) had mean anti-Xa levels in the high therapeutic range. Of 20 patients with no documented response to therapy, 13 (65%) had mean anti-Xa levels in the low therapeutic range and 7 (35%) had mean anti-Xa levels in the high therapeutic range. Forty-eight (79%) of the 61 patients with low-range mean anti-Xa level had any response to therapy. Twenty-one (75%) of the 28 patients with high-range mean anti-Xa level had any response to therapy. Chi-square test (P = 0.080) and logistic regression (OR = 1.23, P = 0.70) demonstrated no significant association between mean anti-Xa range (lower vs. upper) and therapy response. CONCLUSIONS: There was no statistically significant difference between low-range versus high-range mean anti-Xa levels and thrombus resolution. Empiric clinical practices of targeting anti-Xa levels in the higher therapeutic range to achieve better outcomes may not be warranted.

Assessment of an Electronic Intervention in Young Women with Heavy Menstrual Bleeding.

STUDY OBJECTIVE, DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Bleeding disorders (BD) occur in up to 50% of adolescents with heavy menstrual bleeding (HMB). This presents unique challenges to health care providers because of the complexity of treating the condition and such complexity can result in difficulty with patients understanding basic information about their condition, limit communication with medical providers, and patient compliance. The aim of the study was to use an electronic approach to enhance patient compliance with medications used to treat their HMB, and to provide educational access to adolescents with BD. This was a prospective cohort study involving patients in a Young Women's Bleeding Disorder Clinic at a single children's hospital. Subjects were given an iPod Touch (Apple Inc, Cupertino, CA) device (ITD), preloaded with the iPeriod (Winkpass Creations) application. Participants recorded information about their BD that they learned about on BD Web sites, and menses, and medications. Electronic and charted data were collected to monitor compliance with prescribed treatment regimens. All ITD allowed Wi-Fi access to allow teens to explore BD Web sites and knowledge was assessed. RESULTS: Twenty-three of 45 subjects completed the study. The mean age was 14.1 ± 1.9 years. Subjects who were compliant with the ITD (group 1), charted on baseline symptoms, menstrual flow (83.3%), cramps (100%, 23/23), breakthrough bleeding (95.6%, 22/23), mood (95.6%, 22/23), and medication use (91.7%) for a mean of 9.3 ± 3.1 months. Subjects who were nonusers (group 2) did not report on symptoms, their condition, or medication use in the device (n = 22). More than 75% (17/23) of subjects in group 1 used hormones alone or hormones with antifibrinolytic agents to control HMB. No subjects stopped or missed medications who were in group 1 intentionally, and also there were 9 enrollees within this same group who missed a medication related to awaiting the prescription to be filled from pharmacy. In group 2, 17 enrollees missed medications, resulting in 19% (4/22) of these enrollees being admitted to hospital for 1-2 days. In addition, enrollees in group 2 missed more medications on average compared with group 1. No subjects in group 1 required admission for HMB treatment failure during the study period, compared with those in group 2 (P = .006). All subjects in group 1 reported accessing Web sites using their ITD to learn about their BD. Groups 1 and 2 did not differ in the number of medications that were prescribed during the time frame (P = .77) or the number of follow-up clinic visits (P = .49). Furthermore, those in group 1 reported fewer breakthrough bleeding episodes than those in group 2 according to clinic notes (P = .03). Users of the ITD were given a set of knowledge questions. Group 2 subjects were not consistent users of the ITD use and did not complete the knowledge questions. Group 1 and 2 could not be compared with regard to knowledge as a result. CONCLUSION: ITD is an excellent tool for adolescents with HMB and BD to allow self-monitoring, provider monitoring, and improve educational access through engaging technology; compliance with device use was associated with several parameters suggestive of improved clinical outcomes.

Risk factors and co-morbidities in adolescent thromboembolism are different than those in younger children.

INTRODUCTION: In adolescent thromboembolism (TE), multiple risk factors (RFs) and co-morbidities (CMs) are reported, though overall prevalence has not been evaluated. We hypothesized that the spectrum of RFs/CMs in adolescent TE differs from children overall and sought to review Texas Children's Hospital's experience. PATIENTS/METHODS: Medical records of adolescents aged 12-21years, diagnosed with arterial or venous TE (AT/DVT) from 2004 to 2014, were retrospectively reviewed and analyzed with IRB approval. RESULTS: Sixty-four adolescents (median age 16, range 12-20years) met study criteria. Fifty-seven (89%) had DVT and six (9%) had AT. Associated RFs/CMs included obesity (47%), CVC (27%), infection (27%), surgery (27%), autoimmune disease (19%), immobility (22%), anatomical abnormality (20%), cancer (8%), estrogen therapy (6%), tobacco use (6%), trauma (3%), inherited thrombophilia (19%), and other medical conditions (11%). Fifty-two (81%) had ≥2 RFs/CMs. Therapy included anticoagulants, antiplatelet agents, and interventional therapy. Of those with follow-up imaging, 49 had complete or partial resolution, 5 had no change and 4 had progression. Fourteen (22%) had recurrent TE. The majority with recurrent TE (79%) had ≥2 RFs at initial diagnosis. Mean time to recurrence was 4.80years; time to recurrence was shorter for occlusive TE (p=0.026). CONCLUSION: Adolescent TE is often multi-factorial with the majority having ≥2 RFs at diagnosis, suggesting the need for detailed evaluation for RFs in this population, which may enable optimal management including thromboprophylaxis, and institution of RF-modifying strategies to prevent occurrence/recurrence.

Prevalence and Severity of Anemia in Children Hospitalized with Acute Heart Failure.

OBJECTIVE: Anemia is common among adult heart failure patients and is associated with adverse outcomes, but data are lacking in children with heart failure. The purpose of this study was to determine the prevalence of anemia in children hospitalized with acute heart failure and to evaluate the association between anemia and adverse outcomes. DESIGN: Review of the medical records of 172 hospitalizations for acute heart failure. SETTING: Single, tertiary children's hospital. PATIENTS: All acute heart failure admissions to our institution from 2007 to 2012. INTERVENTIONS: None. OUTCOME MEASURES: Composite endpoint of death, mechanical circulatory support deployment, or cardiac transplantation. RESULTS: Patients ages ranged in age from 4 months to 23 years, with a median of 7.5 years, IQR 1.2, 15.9. Etiologies of heart failure included: dilated cardiomyopathy (n = 125), restrictive cardiomyopathy (n = 16), transplant coronary artery disease (n = 18), ischemic cardiomyopathy (n = 7), and heart failure after history of congenital heart disease (n = 6). Mean hemoglobin concentration at admission was 11.8 g/dL (±2.0 mg/dL). Mean lowest hemoglobin prior to outcome was 10.8 g/dL (±2.2 g/dL). Anemia (hemoglobin <10 g/dL) was present in 18% of hospitalizations at admission and in 38% before outcome. Anemia was associated with increased risk of death, transplant, or mechanical circulatory support deployment (adjusted odds ratio 1.79, 95% confidence interval = 1.12-2.88, P = .011). For every 1 g/dL increase in the patients' lowest hemoglobin during admission, the odds of death, transplant, or mechanical circulatory support deployment decreased by 18% (adjusted odds ratio = 0.82, 95% confidence interval = 0.74-0.93, P = 0.002). CONCLUSIONS: Anemia occurs commonly in children hospitalized for acute heart failure and is associated with increased risk of transplant, mechanical circulatory support, and inhospital mortality.

Algorithm for analysis of administrative pediatric cancer hospitalization data according to indication for admission.

BACKGROUND: Childhood cancer relies heavily on inpatient hospital services to deliver tumor-directed therapy and manage toxicities. Hospitalizations have increased over the past decade, though not uniformly across childhood cancer diagnoses. Analysis of the reasons for admission of children with cancer could enhance comparison of resource use between cancers, and allow clinical practice data to be interpreted more readily. Such comparisons using nationwide data sources are difficult because of numerous subdivisions in the International Classification of Diseases Clinical Modification (ICD-9) system and inherent complexities of treatments. This study aimed to develop a systematic approach to classifying cancer-related admissions in administrative data into categories that reflected clinical practice and predicted resource use. METHODS: We developed a multistep algorithm to stratify indications for childhood cancer admissions in the Kids Inpatient Databases from 2003, 2006 and 2009 into clinically meaningful categories. This algorithm assumed that primary discharge diagnoses of cancer or cytopenia were insufficient, and relied on procedure codes and secondary diagnoses in these scenarios. Clinical Classification Software developed by the Healthcare Cost and Utilization Project was first used to sort thousands of ICD-9 codes into 5 mutually exclusive diagnosis categories and 3 mutually exclusive procedure categories, and validation was performed by comparison with the ICD-9 codes in the final admission indication. Mean cost, length of stay, and costs per day were compared between categories of indication for admission. RESULTS: A cohort of 202,995 cancer-related admissions was grouped into four categories of indication for admission: chemotherapy (N=77,791, 38%), to undergo a procedure (N=30,858, 15%), treatment for infection (N=30,380, 15%), or treatment for other toxicities (N=43,408, 21.4%). The positive predictive value for the algorithm was >95% for each category. Admissions for procedures had higher mean hospital costs, longer hospital stays, and higher costs per day compared with other admission reasons (p<0.001). CONCLUSIONS: This is the first description of a method for grouping indications for childhood cancer admission within an administrative dataset into clinically relevant categories. This algorithm provides a framework for more detailed analyses of pediatric hospitalization data by cancer type.

Flow cytometric measurement of microparticles: pitfalls and protocol modifications.

Upon activation, many cells shed components of their plasma membranes as microparticles. Depending on the methods of preparation and analyses, microparticle counts may vary significantly between laboratories, making data analyses and clinical correlations challenging. To assess how variations in sample preparation affect microparticle measurements, blood samples from 13 healthy, adult volunteers were labeled with Annexin V, cell-specific antibodies, and antibodies against tissue factor (TF). Data were acquired and analysed using an EPICS XL-MCL flow cytometer. Annexin V(+) monocyte-, platelet-, endothelial-, or erythrocyte-derived microparticles accounted for 10.4%, 38.5%, 43.8%, and 7.3% of the total number of microparticles (13.7 +/- 3.0 x 10(3)/ml of whole blood), respectively. A similar distribution of cell types was seen for TF(+) microparticles (6.3 +/- 2.6 x 10(3)/ml of whole blood). No statistical difference was noted in microparticle distribution using either 19- or 21-gauge needles. Elevated levels of platelet- and erythrocyte-derived microparticles were detected in heparin and PPACK-anticoagulated samples as compared to samples anticoagulated with ACD or sodium citrate (P < 0.05, student's t-test). Additional centrifugation was critical for removing platelet contamination, which significantly affected microparticle counts. Finally, Annexin V(+) and TF(+) microparticles were significantly reduced upon sample storage at low temperatures. Microparticle levels are significantly affected by variations in sample preparation and storage. These results illustrate the need to standardize assay protocols in order to obtain consistent measurements. Our studies further optimize sample preparation for microparticle detection.

Evaluation of prolonged aPTT values in the pediatric population.

To assess the likelihood of significant bleeding disorders in children with prolonged activated partial thromboplastin times (aPTTs), a retrospective chart review was performed. Data analyses determined that in the absence of symptoms and a negative family history, the diagnosis of a bleeding disorder was unlikely in an individual with a prolonged aPTT (negative predictive value = 80%). Conversely, a prolonged aPTT was predictive (positive predictive value = 62%) in the presence of both clinical symptoms and a documented family history. The scope of laboratory investigation in any child with a prolonged aPTT should be tempered by the clinical presentation and the associated personal and family histories.