Uncaptured rates of postpartum venous thromboembolism: a US national analysis.

OBJECTIVE: To quantify the proportion of postpartum venous thromboembolism (VTE) readmissions, including those that occur at different hospitals from index admission, and describe risk factors for this outcome. DESIGN: Retrospective observational study. SETTING: US hospitals included in the Nationwide Readmissions Database. SAMPLE: A total of 3 719 238 patients >14 years of age with a delivery-associated hospitalisation in 2014. METHODS: Univariate analysis was performed to identify patient and hospital factors associated with readmissions. Significant factors were included in multivariate logistic regression to identify independent risk factors. Results were weighted for national estimates. MAIN OUTCOME MEASURES: Readmission with VTE to both index and different hospitals at 30, 60 and 90 days. RESULTS: The VTE cumulative readmission rate was 0.053% (n = 1477), 0.063% (n = 1765) and 0.069% (n = 1938) at 30, 60 and 90 days, respectively. Patients were readmitted to different hospitals 31% of the time within 90 days. Risk factors for different hospital VTE readmission were unique and included younger age and initial admission to a small/medium-sized hospital. Initial admission to a for-profit hospital increased the likelihood of readmission to a different hospital. CONCLUSIONS: Nearly one in three postpartum VTEs are missed by the current quality metrics, with significant implications for outcomes and quality. For-profit hospitals have a significant portion of their VTE readmissions hidden, falsely lowering their readmission rates relative to public hospitals. TWEETABLE ABSTRACT: US analysis shows 1 in 3 readmissions for postpartum venous thromboembolism currently missed.

Analytical evaluation of the ADAMS™ A1c HA 8180 thalassemia mode high-pressure liquid chromatography analyser for the measurement of HbA2 and HbF.

BACKGROUND: ADAMS™ A1cHA-8180T is a HPLC system; within 3.5 min, it quantifies HbF, HbA2 , and HbA0 and flags abnormal peaks. We evaluate its analytical performance for routine estimation of HbA2 and HbF, and critical tests were performed for identifying ß-thalassemia carriers. METHODS: Trueness imprecision, carry over, linearity, and effect of anemia were evaluated according to ICLH, ICLS, or manufacture's guidelines. Comparison (ADAMS™ A1c HA-8160T) was performed by running 400 samples from healthy subjects, 30 alpha and 80 beta carriers (range: 1.9-5.7 %). RESULTS: Trueness - HbA2 2.7 %, bias 0.81 %; HbA2 5.8 %, bias 0.38 %. HbA2 4.0% is not affected by Hb in the range 221-40 g/L. Carry over was negligible. Within run: normal control - CV 1.5 %, high control - CV 0.9 %.Within laboratory: normal control - total CV% 1.59%; high control - 0.92 %. Linearity - y = 1.034x - 0.17, R2  = 0.998 (range: 2.8-4.8%).Method comparison - y = 0.93x + 0.22, R2  = 0.997. HbF imprecision CVs between 0.66 and 1.24% and trueness between 0 and 2.8%. Linearity - y = 1.088x - 0.27, R2  = 0.999 (0.1-5.7%). CONCLUSIONS: ADAMS™ A1c HA-8180T provides a rapid and reliable separation of HbA2 . The measurement is accurate and reproducible, which is needed because of the slight difference between normal and pathological values. The gap in HbA2 values between normal subjects and ß-thalassemia carriers makes this an appropriate method for rapid screening for carriers.

Percentage of hypochromic erythrocytes and reticulocyte hemoglobin equivalent predictors of response to intravenous iron in hemodialysis patients.

INTRODUCTION: Reticulocyte hemoglobin content and percentage of hypochromic red cells are incorporated into the European best practice guidelines on anemia management in chronic kidney disease. Sysmex XN analyzer (Sysmex Corporation, Kobe, Japan) reports reticulocyte hemoglobin equivalent (Ret-He) and the hypochromic fraction of erythrocytes (%Hypo-He). Our aim was to assess the value of these parameters, in terms of the sensitivity and specificity for detecting functional iron deficiency, in hemodialysis (HD) patients. METHODS: Forty HD patients in the maintenance phase of erythropoietin therapy were included. Intravenous iron supplementation was interrupted at least 3 weeks before recruitment. Two samples were analyzed for each patient: the baseline after the iron-free period and the second sample after 4 weeks of IV iron administration. Hemogram and biochemical parameters of the iron status were measured. Patients were classified as responders or nonresponders to an iron load; responders had an increase in Hb of at least 10 g/L after iron administration, compared to the baseline. To identify the efficiency of the test for predicting the response to iron administration, receiver operating characteristic analysis (ROC) was performed. RESULTS: According to the established criteria, 21 patients were responders and 19 nonresponders. ROC analysis results: Ret-He area under curve (AUC) was 0.84 (95% CI 0.64-0.93), at cutoff 30.8 pg, sensitivity 78.7%, and specificity 87.2%. % Hypo-He AUC was 0.78 (95% CI 0.64-0.91), at cutoff 2.4%, sensitivity 72.2%, and specificity 88.1%. CONCLUSIONS: % Hypo-He and Ret-He are reliable parameters for the study of erythropoiesis status in HD patients.

Local verification between the hematological analyzers Sysmex XN-series and XE-5000.

INTRODUCTION: The aim of this study was to perform a verification of the hematology analyzer Sysmex XN-2000 by comparing with the previous XE-5000. This study assessed the precision and carryover on the XN-2000 and the systematic error between the both counters according to desirable biological variability criterion and a flag comparison study. METHODS: Within-run precision and between-batch precision were measured according to the ICSH guidelines. A comparative study was performed analyzing two hundred and six samples of peripheral blood from patients. The statistical study was conducted using the Passing-Bablok and Bland-Altman analyses. The leucocyte flag comparison was made by measuring the efficiency rate. RESULTS: Between-batch precision was lower than that recommended by the biological variability criterion and manufacturer specifications. The comparison gave nonagreement results for neutrophil and basophil counts according to the criterion of biological variability. Erythroblasts and immature granulocytes showed nonagreement, but there is no available biological variation database for these parameters to compare with. Nevertheless, excellent absolute agreement was found for red blood cell parameters, and for platelet, lymphocyte, monocyte, and eosinophil counts. CONCLUSIONS: The global results obtained for the precision, comparability, and efficiency provide a satisfactory integration of the XN-2000 in the core laboratory routine and accomplish an optimal reliability.

Differential diagnosis of microcytic anemia: the role of microcytic and hypochromic erythrocytes.

INTRODUCTION: Various indices derived from red blood cell (RBC) parameters have been described for distinguishing thalassemia and iron deficiency. We studied the microcytic to hypochromic RBC ratio as a discriminant index in microcytic anemia and compared it to traditional indices in a learning set and confirmed our findings in a validation set. METHODS: The learning set comprised samples from 371 patients with microcytic anemia mean cell volume (MCV < 80 fL), which were measured on a CELL-DYN Sapphire analyzer and various discriminant functions calculated. Optimal cutoff values were established using ROC analysis. These values were used in the validation set of 338 patients. RESULTS: In the learning set, a microcytic to hypochromic RBC ratio >6.4 was strongly indicative of thalassemia (area under the curve 0.948). Green-King and England-Fraser indices showed comparable area under the ROC curve. However, the microcytic to hypochromic ratio had the highest sensitivity (0.964). In the validation set, 91.1% of microcytic patients were correctly classified using the M/H ratio. CONCLUSIONS: Overall, the microcytic to hypochromic ratio as measured in CELL-DYN Sapphire performed equally well as the Green-King index in identifying thalassemia carriers, but with higher sensitivity, making it a quick and inexpensive screening tool.

Erythrocyte and reticulocyte indices in the assessment of erythropoiesis activity and iron availability.

INTRODUCTION: Consequence of the imbalance between the erythroid marrow iron requirements and the actual supply is a reduction in red cell hemoglobin content, which causes hypochromic mature red cells and reticulocytes. Sysmex XE 5000 analyzer (Sysmex Corporation, Kobe, Japan) reports reticulocyte hemoglobin equivalent (Ret-He) and the percentages of erythrocyte subsets, including the hypochromic fraction (%Hypo-He). We study the value of these parameters of hemoglobinization in the evaluation of erythropoiesis and iron availability. METHODS: Ninety healthy subjects, 85 patients with chronic kidney disease (CKD) and 65 patients on dialysis (HD) receiving therapy and 91 patients with iron deficiency (IDA) were analyzed. Pearson's correlation, t-test for independent, and receiver operating characteristic (ROC) curve analysis were utilized. RESULTS: The results in the IDA group reflected the state of iron depletion (low ferritin), low iron availability (low MCH and high percentage of hypochromic red cells (%Hypo-He)), and iron-restricted erythropoiesis (low Ret-He). In the HD and CKD, the reticulocyte percentage showed the increased erythropoiesis, maintained due to treatment (Ret-He over 30 pg) and good iron availability, MCH within reference range and %Hypo-He slightly increased. The results of ROC curves analysis for the diagnosis of iron deficiency (gold standard sTfR > 21 nm) were as follows: Ret-He area under curve (AUC) 0.935 cutoff 29.8 pg, sensitivity 90.7%, specificity 83.1%. % Hypo-He AUC 0.925 cutoff 3.5%, sensitivity 87.3%, specificity 88.0%. CONCLUSIONS: Percentage of hypochromic red cells and Ret-He provide information about individual cell characteristics, so the hypochromic cells are detected and quantitated improving the evaluation of erythropoiesis and iron status.

Low hemoglobin density potential marker of iron availability.

INTRODUCTION: Low hemoglobin density (LHD%) is a new parameter provided by Beckman-Coulter derived from the mean cell hemoglobin concentration, using the mathematical sigmoid transformation LHD% = 100×√(1-(1/(1 + e(1.8(30-MCHC)))). This study investigated the reliability of LHD% for the assessment of iron status in the presence of inflammation. METHODS: Healthy subjects (n = 90) and patients with iron deficiency (IDA, n = 110), chronic kidney disease (CKD, n = 65) and anemia of chronic disease (ACD, n = 85; 24 were iron deficient and 61 were iron sufficient) were analyzed on a LH 780 analyzer (Beckman Coulter Inc., Miami, FL, USA). Independent samples U test and receiver operating characteristic (ROC) curve analysis were applied. To determine the concordance between LHD% and soluble transferrin receptor (sTrR) Cohen's κ index was calculated. RESULTS: LHD % values showed no statistical difference in patients with IDA and patients with ACD accompanied with IDA (P = 0.6427); LHD% values in these patients were significantly different (P < 0.0001) compared with the iron-sufficient patients with ACD. ROC analysis for LHD% in the detection of iron deficiency showed the following: area under curve 0.903; cut off 5.5%, sensitivity 88.6%, specificity 76.9%; κ index, 0.65. CONCLUSION: LHD% is a reliable parameter for the detection of iron deficiency in patients with anemia in the presence of inflammation.

Analysis of reticulocyte parameters on the Sysmex XE 5000 and LH 750 analyzers in the diagnosis of inefficient erythropoiesis.

The reticulocyte hemoglobin equivalent (Ret He) represents an indirect measure of the functional iron available for erythropoiesis over the previous 2-3 days. Only the analyzers of a single manufacturer, Sysmex (Sysmex Corporation, Kobe, Japan), include Ret He. Red blood cell size factor (RSf) is a new parameter provided by Beckman Coulter, which joins together the volume of the erythrocytes and the volume of reticulocytes. The aims of the study were to investigate the clinical usefulness of RSf in the study of erythropoiesis status and to assess its concordance with Ret He values. Samples from 417 patients were run on both LH 780 (Beckman Coulter) and Sysmex XE 5000 analyzers. Independent samples t-test, Pearson correlation, receiver operating characteristic (ROC) analysis and inter-rater reliability (κ index) were applied. Good correlation between RSf and Ret He was observed, r = 0.8184. Significant differences (P < 0.001) were detected when groups with inefficient erythropoiesis were compared with patients undergoing therapy and healthy subjects. ROC analysis for RSf in the diagnosis of inefficient erythropoiesis, cutoff 91.1 fl, area under curve 0.963, sensitivity 91.7%, specificity 88.5%. Concordance between RSf and Ret He κ = 0.68. RSf and Ret He are suitable parameters for the assessment of erythropoiesis status.

The role of automated measurement of red cell subpopulations on the Sysmex XE 5000 analyzer in the differential diagnosis of microcytic anemia.

Cell counter-based formulae have been used in the differential diagnosis of microcytic anemia. The measurement of new red cell parameters is now available on the Sysmex XE 5000 analyzer. Derived from the percentages of microcytic and hypochromic red cells, the authors describe the new formula %microcytic-%hypochromic, M-H index. The aim of this study was to assess the discriminant value of this new index in the differential diagnosis of microcytic anemia and thalassemia screening compared to the published indices. Receiver operating characteristic curves, sensitivity, specificity and Youden index were calculated for a set of 170 iron-deficiency anemia patients and 200 ß thalassemia carriers. % microcytic-% hypochromic index showed the best area under the curve (area under curve AUC, 0.994) and Youden index (93.9%), among considered indices; 98% sensitivity, 95.9% specificity, at a cutoff value >11.5; Green and King index ranked second (AUC 0.99, Youden index 90.8%). Because of high sensitivity and specificity, the new index %microcytic-%hypochromic was the most reliable index evaluated. M-H index could be a useful tool in the differential diagnosis of microcytic anemia, and samples with M-H>11.5 can be chosen for further analysis to confirm the diagnosis of thalassemia.

The new mature red cell parameter, low haemoglobin density of the Beckman-Coulter LH750: clinical utility in the diagnosis of iron deficiency.

The percentage of hypochromic red cells (%Hypo) is a diagnostic tool that has been used with biochemical markers to diagnose iron disturbances and is incorporated to National Kidney Foundation KDOQI guidelines for monitoring recombinant human erythropoietin therapy. %Hypo measurement has been restricted to analysers manufactured by Siemens. Low haemoglobin density (LHD%), a new parameter provided by Beckman-Coulter, is derived from the traditional mean cell haemoglobin concentration (MCHC), using the mathematical sigmoid transformation [see equation in text]. This study aimed to establish LHD% values in the normal population and in different types of anaemia, to investigate its clinical usefulness in the study of iron status and its correlation with %Hypo. Samples from 449 patients [120 healthy individuals, 86 iron deficiency anaemia (IDA), 102 chronic kidney disease, 58 anaemia of chronic disease and 83 beta-thalassaemia carriers] were run sequentially on the LH 750 (Beckman-Coulter) and Advia 2120 (Siemens) analysers. The reliability of LHD% as a marker of iron deficiency was evaluated on a group of 152 consecutive patients with IDA. Good correlation was observed between %Hypo and LHD%, r(2) = 0.869. Receiver operating characteristic curve analysis for LHD% and the diagnosis of iron deficiency was: cut-off point 4.0%; area under the curve 0.976; sensitivity 95.2%; specificity 93.3%. There was a good level of agreement between LHD% and %Hypo. Both are suitable parameters for determining iron status and its availability for erythropoiesis, with the same clinical significance.

Clinical utility of the new Beckman-Coulter parameter red blood cell size factor in the study of erithropoiesis.

CHr has been used as a diagnostic tool, together with biochemical markers, to distinguish IDA from ACD, and is incorporated to NKF-K/DOQI guidelines for the monitoring of rHuEPO therapy. The measurement of CHr has been restricted to the analysers of a single manufacturer, Siemens. Red blood cell size factor (RSf) is a new parameter provided by Beckman-Coulter which joins together the volume of erythrocytes and the volume of reticulocytes Rsf = square root (MCV x MRV). The aims of the study were to establish the values of RSf in normal population and in different types of anemia to investigate its clinical usefulness in the study of erythropoiesis and its correlation with CHr. Samples from 449 patients (learning group) were run sequentially on both LH 750 (Beckman-Coulter) and Advia 2120 (Siemens) analysers. Good correlation between CHr and RSf was observed, r(2) = 0.85. Receiver operating characteristic curve analysis for RSf and the diagnosis of restricted erythropoiesis. [table: see text] The diagnostic usefulness of RSf was evaluated on a validation group which included 220 consecutive patients with anemia. This study shows a very good level of agreement between RSf and CHr. Both are suitable parameters for the study of erythropoiesis.

Red blood cell microcytosis and hypochromia in the differential diagnosis of iron deficiency and beta-thalassaemia trait.

Iron deficiency anaemia (IDA) and beta-thalassaemia are the most common causes of microcytic anaemia. Some indices have been defined to quickly discriminate this diseases based on red cell parameters obtained from automated blood cell analyzers, and can be effective for use as a preliminary screening tool to allow the reflex HbA(2) analysis, when a proper cut-off is chosen. Advia 2120 (Siemens Medical Solutions Diagnostics) directly measures volume and haemoglobin concentration of individual red cells, and quantifies the percentage of microcytic, normocytic, macrocytic, hypochromic, normochromic and hyperchromic red cells. Because of the inverse behaviour of the % microcytic and % hypochromic red cells in beta-thalassaemia trait and in IDA the ratio between these two values was computed and its discriminant efficiency assessed. The aim of the study was to assess the predictive value of the new index % microcytic/% hypochromic ratio in the differential diagnosis of beta-thalassaemia compared with Mentzer index, currently used in our Laboratory. Sensitivity, specificity and total efficiency of both indices were calculated for a set of 110 IDA patients and 150 beta-thalassaemia carriers. Discriminant efficiency was similar for both indices.

Clinical pharmacokinetics of high-dose DTIC.

The pharmacokinetics of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC, dacarbazine) given at a dose of 850-1,980 mg/m2 as a 10- to 30-min infusion was studied in cancer patients, and the plasma concentration-time curves were adjusted to a two-compartment model, with a mean t1/2 alpha value of 0.17 h (range, 0.1-0.26 h) and a mean t1/2 beta value of 2 h (range, 1.5-2.7 h) being found. The mean volume of the central compartment of (Vc) and the apparent volume of distribution (VB) were 0.42 1 kg-1 (range, 0.24-0.54 1 kg-1) and 1.49 1 kg-1 (range, 0.88-1.74 1 kg-1), respectively. The mean total body clearance of DTIC was 0.58 1 kg-1 h-1 (range, 0.26-0.82 1 kg-1 h-1), and the mean renal clearance was 0.28 1 kg-1 h-1 (range, 0.17-0.49 1 kg-1 h-1). Unchanged DTIC recovered from urine within 24 h varied from 11% to 63% of the delivered dose, with an inverse correlation being found between the DTIC dose and the amount excreted. The metabolite aminoimidazole carboxamide (AICA) was detectable in plasma from the start of DTIC infusion, and its concentration-time curve showed a monophasic decay, exhibiting a mean t1/2 value of 3.25 h (range, 1.77-5.82 h). Mean AICA renal clearance was 0.15 1 kg-1 h-1 (range, 0.05-0.32 1 kg-1 h-1). The amount of AICA excreted in urine increased with increasing DTIC dose and varied from 1.2% to 13.6% of the delivered DTIC dose. Both DTIC distribution and disposition and AICA production and renal excretion seemed to be limited after high DTIC doses as compared with the pharmacokinetics of low-dose DTIC. Nonlinear pharmacokinetics for high-dose DTIC could not be clearly excluded.