Absolute immature platelet count dynamics in diagnosing and monitoring the clinical course of thrombotic thrombocytopenic purpura.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening diagnosis requiring prompt initiation of therapeutic plasma exchange (TPE). Measurement of immature platelet (PLT) fraction (%-IPF) differentiates PLT consumption or destruction from hypoproduction. STUDY DESIGN AND METHOD: Our study evaluated %-IPF changes over the course of TTP treated with TPE and as a measure of treatment efficacy. Eleven idiopathic TTP patients, two human immunodeficiency virus (HIV)-associated TTP patients, and five non-TTP patients with thrombocytopenia were enrolled into our study. All patients were treated with TPE and had ADAMTS13 activity measured. RESULTS: All idiopathic TTP patients had a significantly increased %-IPF and decreased absolute immature PLT count (A-IPC) and PLT count at presentation. An A-IPC value of less than 5 × 10(9) /L at presentation has 84.6% sensitivity, 80% specificity, and 91.7% positive predictive value for diagnosing TTP. A concurrent steady decline in %-IPF and increased PLT counts toward normal was observed in TTP patients undergoing TPE. The A-IPC, however, showed an increase and decrease curve that was not seen in the two HIV-associated TTP patients with no response to TPE and the five non-TTP patients. More importantly, reaching an A-IPC ratio of 3 compared to baseline value during TPE can readily differentiate idiopathic TTP from the other two groups and is correlated with good clinical responses to TPE. An abrupt increase of A-IPC during TPE was also noted in a TTP patient who relapsed 3 days before PLT count decrease. A-IPC is positively correlated with ADAMTS13 activity at presentation but negatively correlated with ADAMTS13 activity during recovery. CONCLUSION: A-IPC should be routinely analyzed for diagnosing and monitoring TTP patients.

Adult and child automated immature granulocyte norms are inappropriate for evaluating early-onset sepsis in newborns.

AIM: Automated haematology analysers are increasingly being used. Normal ranges for automated immature granulocyte counts (IG%) are described in adults and children as <1%, but are not reported for newborns, who often have complete blood count with differential in evaluation for early-onset sepsis. Therefore, this study aimed to describe IG% during the first 48 hours of life (HOL) in newborns and determine the clinical factors affecting IG%. METHODS: We carried out retrospective chart reviews for newborns ≥35 weeks gestational age with one or more complete blood count with differential in the first 48 HOL. Clinical history and automated haematology results were reviewed. RESULTS: Forty-seven of 215 subjects had two or more complete blood counts within 48 h. In the first 48 HOL, IG% ranged from 0 to 8.4% (95th percentile 5.2%). At <12 h, 70% of samples had IG% >1%. IG% appears to decrease over time. Earlier hour of life and higher birth weight were independently associated with higher IG%. CONCLUSION: Immature granulocyte counts in newborns appeared to be higher than reported for other age groups. Use of adult and child norms for IG% would not be appropriate for newborns being evaluated for early-onset sepsis.

(18F)-FDG-PET/MRI of unicentric retroperitoneal Castleman disease in a pediatric patient.

Castleman disease (CD) is a rare lymphoproliferative disorder of unknown etiology that may occur anywhere in the lymphatic system. Imaging plays an important role in detecting and staging this disease. Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) combines the metabolic information derived from nuclear medical imaging with the high soft tissue resolution from MRI. We review the features of CD in standard diagnostic imaging, analyze the specific imaging findings of CD in FDG-PET/MRI and discuss a potential benefit of PET/MRI based on the case of a 15-year-old female patient with retroperitoneal CD.

A New Automated Technology for Cerebrospinal Fluid Cell Counts: Comparison of Accuracy and Clinical Impact of GloCyte, Sysmex XN, and Manual Methods.

OBJECTIVES: The purpose of the study was to compare the performance of GloCyte (Advanced Instruments, Norwood, MA), a new semiautomated instrument for cerebrospinal fluid cell counting, with the manual hemocytometer method and the automated Sysmex XN (Sysmex, Kobe, Japan) body fluid mode. The clinical impact of replacing the manual method with either automated method was determined. METHODS: Fifty-seven samples from 38 patients were analyzed by all three methods. Pearson correlation and Passing-Bablok regression were used to compare methods. Cytospin smears were reviewed on all samples, and clinical histories were obtained. RESULTS: There was a strong linear relationship between the manual and automated methods for WBC counts ( R = 0.988 for GloCyte; R = 0.980 for Sysmex XN). Positive bias was absent or negligible for WBC counts less than 30/µL. GloCyte and manual RBC counts were equivalent. There were no samples for which replacement of manual WBC counts by automated counts would have changed the diagnosis. Both automated methods showed improved precision for WBC counts compared with the manual method. CONCLUSIONS: Replacing manual WBC counts by GloCyte or Sysmex XN WBC counts would improve consistency of results without compromising diagnostic accuracy.

Posttransplant lymphoproliferative disorder after umbilical cord blood transplantation in children.

Reported are 7 cases of posttransplant lymphoproliferative disorder (PTLD) arising in children who received umbilical cord blood transplantation (UCBT). There were 4 females and 3 males with a median age of 3 years (range, 1-16 years). All 7 patients received UCBT, including 1 patient who received multiple units and 1 transplanted under nonmyeloablative condition. The time interval from UCBT to PTLD averaged 4 months (range, 2 weeks to 9 months). Patients typically presented with high-stage disease with visceral organ involvement. Histology of the PTLDs showed monomorphic morphology in 5 cases and polymorphic morphology in the remaining 2 cases. Bone marrow biopsies were performed in 3 cases and were negative for PTLD. Epstein-Barr virus (EBV) was detected in the PTLD in all 7 patients by in situ hybridization. Evidence of past EBV infection was found in the recipients, but the EBV genome was not detected in the donor cord blood samples, suggesting that donor cord blood was not the source of EBV infection. The origin of the PTLD was investigated in 5 cases. PTLD was of host origin in 2 patients who failed engraftment and of donor origin in the remaining 3 patients who had complete engraftment. Four of 5 patients with monomorphic PTLD failed to demonstrate significant responses to rituximab and/or reduction of immunosuppression and died within 1 month after diagnosis. The remaining 2 patients with polymorphic PTLD showed complete response to therapy. One patient was alive 35 months after transplant, and the other patient died of infection 6 months after transplant. It is concluded that PTLD arising after UCBT in children occurs early after transplant and represents a serious EBV-related complication. PTLD may be of donor or recipient origin depending on engraftment status. Both monomorphic and polymorphic histology may be seen, and monomorphic histology appears to predict an unfavorable prognosis.

The detection and diagnosis of hemoglobin A2' by high-performance liquid chromatography.

Hemoglobin (Hb) A2' is a hematologically silent variant of HbA2 that is detected easily by high-performance liquid chromatography (HPLC), where it elutes in the S window. Our purposes were to define diagnostic criteria for the HbA2' trait using the Variant II (Bio-Rad, Hercules, CA) and to determine the prevalence of HbA2' in a metropolitan patient population. All Hb screens (N = 5,862) performed during a 26-month period were reviewed for new hemoglobinopathies. We identified 57 cases of HbA2' trait, making it the fourth most prevalent Hb variant detected in this population after HbS, HbC, and beta-thalassemia minor For HbA2' trait cases, the mean HbA2 level was 1.7% (SD, 0.17%), and the mean HbA2' level was 1.3% (SD, 0.18%). Six possible HbA2'/beta-thalassemia double heterozygotes were identified, for whom the sum of the HbA2 and HbA2' exceeded 4% of total Hb. Hb variants that might interfere with detection of HbA2' include HbS, glycosylated HbC, and HbG2. Diagnostic criteria proposed for the HbA2' trait by HPLC are HbA2 of 2% or less, S window peak of 1% to 2%, no previous diagnosis of HbS, and absence of HbG and HbC.

Performance of an automated immature granulocyte count as a predictor of neonatal sepsis.

Neonatologists use immature granulocytes (IG) in manual differential counts as an indicator of sepsis. This study was designed to compare the predictive ability of automated vs manual IG counts for neonatal sepsis. Infants undergoing sepsis evaluation were identified prospectively for study if a CBC count was obtained in temporal proximity to the blood culture. Automated IG counts were obtained from the research software of the Sysmex XE-2100 (Sysmex, Kobe, Japan). Manual average IG counts were obtained from two 100-cell manual differential counts independently performed by a technologist and a hematopathology resident. A comparative analysis of manual and automated IG counts showed considerable overlap of ranges. The highest positive blood culture rate occurred in the nonneutropenic preterm subset of infant older than 7 days (21/55 [38%]). For these infants, elevated IG counts by manual and automated methods were associated significantly with positive blood culture results (odds ratio, manual, 3.74; odds ratio, automated, 3.63), albeit with low sensitivity.

Body fluid cell counts by automated methods.

Automated cell counting for body fluids is gradually replacing manual cell counting by hemocytometer. Automation offers potential benefits of improved accuracy, efficiency, and standardization. The addition of body fluid modes to some hematology analyzers adapts the technology and software to meet the particular requirements of body fluid analysis. However, the functional sensitivity for low cell counts currently limits applicability of automated methods to all types of body fluid. Microscopic review is indicated when malignancy is a diagnostic consideration.

How useful are CBC and reticulocyte reports to clinicians?

We surveyed 1,353 attending and 689 house staff physicians of the University Hospitals of Cleveland to ascertain the parameters of the CBC, leukocyte differential, and reticulocyte reports perceived as useful in clinical practice. The response rate was 33% for attending and 22% for house staff physicians. Only 4 of 11 parameters routinely reported in the CBC battery were selected as frequently or always useful by more than 90% of physicians: hemoglobin, hematocrit, platelet count, and WBC count. Among primary care physicians, the mean cell volume also attained this level of usefulness for the evaluation of anemia. There were no differences between academic physicians and community physicians in the use of RBC indices; however, physicians who had been in practice for fewer than 10 years indicated higher use of the red cell distribution width than physicians practicing for more than 10 years. Most physicians prefer differentials reported as percentages rather than absolute counts. Among physicians who monitor reticulocyte counts, the immature reticulocyte fraction is not widely used. Our results indicate that many physicians do not use much of the data provided in routine CBC/differential and reticulocyte reports. Some modifications of report formats may facilitate physician perception of hematology laboratory results.

Platelet counting by the coulter LH 750, sysmex XE 2100, and advia 120: a comparative analysis using the RBC/platelet ratio reference method.

We compared the accuracy and precision of the impedance platelet counts generated by the Beckman Coulter LH 750 and the Sysmex XE 2100 and the optical platelet counts produced by the Advia 120 and the Sysmex XE 2100 withflow cytometric reference platelet counts. Samples analyzed had platelet counts less than 150 x 10(3)/microL (150 x 10(9)/L) with a platelet flag or less than 75 x 10(3)/microL (75 x 10(9)/L) on the Sysmex SE 9500. The 105 samples were run sequentially through each analyzer. Anti-CD41 and anti-CD61 monoclonal antibodies were used for flow cytometric determination of the reference platelet count by the RBC/platelet ratio method. The Beckman Coulter and the Sysmex impedance platelet counts showed better correlation with the reference method than the optical platelet counts by the Advia and the Sysmex. At platelet transfusion thresholds of 10 and 20 x 10(3)/microL (10 and 20 x 10(9)/L), the precision of the impedance methods was somewhat better than that of the optical methods. Current methods of optical platelet counting may not be superior to impedance platelet counts for all patient populations.

Automated cerebrospinal fluid cell counts using the Sysmex XE-5000: is it time for new reference ranges?

The main objectives of the study were to compare manual and automated WBC counts on clear cerebrospinal fluid (CSF) samples. Clear CSF samples from 200 adults and children were studied. Cell counts were performed manually using a hemocytometer and then analyzed on the Sysmex XE-5000. Descriptive statistics and Spearman correlation for nonparametric data were used for method comparison. Manual WBC counts ranged from 0 to 702 cells/µL, and Sysmex counts ranged from 0 to 629 cells/µL. The Spearman rank correlation coefficient for the entire range of data was 0.77 (P < .001); however, the correlation was weaker at the low end of the data spectrum. For manual WBC ranges of 0 to 5 cells/µL and 0 to 10 cells/µL, the corresponding Sysmex 0 to 95th percentile ranges were 0 to 23 cells/µL and 0 to 27 cells/µL, respectively. The results suggest that larger studies are necessary to determine new reference ranges for automated CSF WBC counts.

Measuring the clinical impact of pathologist reviews of blood and body fluid smears.

CONTEXT: Despite the widespread practice of pathologist review of blood and body fluid smears, little is known about its impact on improving patient care. OBJECTIVE: To assess the clinical usefulness of pathologist review of blood and body fluid smears. DESIGN: Survey study. Pathology residents contacted the ordering physician after pathologist reviews were reported to assess their clinical impact. RESULTS: Ninety-six pathologist reviews met criteria for study inclusion, and 64 ordering physicians were successfully contacted during the 2-month study period. Of the 64 cases, 19 reviews (30%) had been seen by the physician within 24 to 48 hours after the report was issued and 33 (51%) had not been seen; in 4 (6%) instances, physicians did not remember whether they had seen the review. Eight reviews (13%) were considered urgent enough to warrant immediate communication by the pathologist. Of the 27 reviews that were seen or directly communicated, 23 (85%) contributed to clinical diagnosis and/or patient management. CONCLUSIONS: This study demonstrates the contribution of pathologist reviews of blood and body fluids to clinical diagnosis and patient management. The results also highlight the problem of a lack of physician awareness of clinical pathology results.