A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura.

The safety and efficacy of weekly rituximab 375 mg/m(2) (×4), given within 3 days of acute TTP admission, with standard therapy (PEX and steroids) was evaluated. Clinical outcomes were compared to historical controls (n = 40) who had not received rituximab. Within the trial group, 15 of 40 required ICU admission and 15% of all cases with the highest troponin T levels on admission were ventilated. Before the second rituximab infusion, 68% of cases had a platelet count > 50 × 10(9)/L and 38% > 150 × 10(9)/L. Fewer PEX were required in whites compared to nonwhite in the rituximab group (mean 14 vs 21, P = .0095). Inpatient stay was reduced by 7 days in the non-ICU trial cases compared to historical controls (P = .04), especially in whites, with a mean reduction of 7 days (P = .05). Ten percent of trial cases relapsed, median, 27 months (17-31 months), compared to 57% in historical controls, median 18 months (3-60 months; P = .0011). There were no excess infections or serious adverse events with rituximab. In conclusion, rituximab appears a safe and effective therapy. Inpatient stay and relapse are significantly reduced in the rituximab cohort. Rituximab should be considered in conjunction with standard therapy on acute presentation of TTP. This study was registered at www.clinicaltrials.gov as NCT009-3713.

Performance evaluation of a new small-volume coagulation monitor: the SmartCheck INR system.

The SmartCheck INR (Unipath, Bedford, England) is a point-of-care device for professional and patient self-monitoring of oral anticoagulant therapy. It measures the international normalized ratio (INR) and assesses test strip integrity, temperature, and sample quality. No significant differences were found in SmartCheck INR results from 3 different instruments or in 3 test-strip lots. Within run imprecision was 0.89% and 6.36% for low and high control samples, respectively (mean INR, 0.99 and 4.08, respectively). Comparability was assessed in 68 patients receiving warfarin by using PTHS Plus (Instrumentation Laboratory, Lexington, MA) and Innovin (Dade Behring, Marburg, Germany) thromboplastins. Good correlations were observed between the methods (r = 0.89 and r = 0.90, respectively) with no significant differences in means: SmartCheck INR, 2.82; Innovin, 2.75; PTHS Plus, 2.74. Clinical agreement with laboratory methods was 88% for Innovin and 97% for PTHS Plus. The SmartCheck INR was easy to use with no mechanical failures during the evaluation and a low test-strip failure rate of 4.7%. The SmartCheck INR provides accurate and reproducible results and is suitable for routine monitoring of oral anticoagulant therapy in the majority of patients.

Performance evaluation of the Sysmex haematology XN modular system.

BACKGROUND: The Sysmex XN haematology instrument performs automatic reflex testing, depending on sample results. A nucleated red blood cell (NRBC) count is provided on all samples. The instrument has a smaller footprint (34%) than previous Sysmex XE analysers. METHODS: An evaluation comparing all results to the Sysmex XE-2100 and manual microscopic differential and morphology (n=390) was performed followed by a workflow study of 1000 samples to compare speed of operation and number of blood films reviews required from both systems. RESULTS: The new features on the instrument are: (1) white cell and NRBC channel, all samples include the NRBC count; (2) white cell precursor channel: false positive flags for blasts, abnormal lymphocytes and atypical lymphocytes are reduced significantly without a statistical increase of false negatives; (3) low white cell count mode: suggested setting of <0.5×10(9)/l. An extended count is more precise and provides an accurate differential. Fluorescent platelet count is performed in a dedicated channel. If the red cell or platelet size histograms are abnormal or if the platelet count is low, then a fluorescent platelet count is automatically performed. Good correlation with the XE-2100 and manual differential was found and the improved results compared to the reference flow cytometric analysis for platelet counts, especially below 30×10(9)/l (XE-2100, R(2)=0.500; XN, R(2)=0.875). CONCLUSION: The XN showed reduced sample turnaround time of 10% and reduced number of blood films for examination, 49% less than the XE-2100 without loss of sensitivity with more precise and accurate results on low cell counts.

The accuracy of platelet counting in thrombocytopenic blood samples distributed by the UK National External Quality Assessment Scheme for General Haematology.

A knowledge of the limitations of automated platelet counting is essential for the effective care of thrombocytopenic patients and management of platelet stocks for transfusion. For this study, 29 external quality assessment specimen pools with platelet counts between 5 and 64 × 10(9)/L were distributed to more than 1,100 users of 23 different hematology analyzer models. The same specimen pools were analyzed by the international reference method (IRM) for platelet counting at 3 reference centers. The IRM values were on average lower than the all-methods median values returned by the automated analyzers. The majority (~67%) of the automated analyzer results overestimated the platelet count compared with the IRM, with significant differences in 16.5% of cases. Performance differed between analyzer models. The observed differences may depend in part on the nature of the survey material and analyzer technology, but the findings have implications for the interpretation of platelet counts at levels of clinical decision making.

Improved flagging rates on the Sysmex XE-5000 compared with the XE-2100 reduce the number of manual film reviews and increase laboratory productivity.

Hematology analyzers generate suspect flags in the presence of abnormal cells. False-positive rates for flags are high on all analyzers. Sysmex, Kobe, Japan, has developed new software for its XE-5000 with improved algorithms for flagging blast cells, abnormal lymphocytes or lymphoblasts, and atypical lymphocytes. This study evaluated the efficiency of these flags in 1,002 samples. The XE-5000 was compared with the XE-2100 (Sysmex) and microscopic examination of cell morphologic features. On the XE-2100, the blast flag demonstrated 90 false-positives, 13 true-positives, and 3 false-negatives. The values on the XE-5000 were 27 false-positives, 14 true-positives, and 2 false-negatives. The abnormal lymphocyte/lymphoblast flag was assessed with the atypical lymphocyte flag. The XE-2100 showed 114 false-positives, 23 true-positives, and 20 false-negatives, and on the XE-5000, there were 45 false-positives, 22 true-positives, and 21 false-negatives. This more specific flagging reduces the number of films that require manual review.

A randomised control trial of patient self-management of oral anticoagulation compared with patient self-testing.

Several studies suggest that patient self-management (PSM) may improve the quality of oral anticoagulation therapy as measured by time spent within the international normalised ratio (INR) target range. We performed a prospective randomised control trial to determine whether the improvement in quality of treatment afforded by PSM is greater than that achieved by patient self-testing (PST) alone. A total of 104 of 800 eligible patients aged 22-88 years (median = 59.8), attending our hospital anticoagulant clinic and receiving long-term warfarin for >8 months agreed to participate. Patients were randomised to PSM (n = 55) or PST (n = 49). Both groups measured their INR using the CoaguChek S every 2 weeks or more frequently if required, for a period of 6 months. Seventy-seven of 104 (74%) patients completed the study (PSM = 41 and PST = 36). The 'drop out' rates for both groups were similar. There was no significant difference between the percentage time in target therapeutic range for PSM (69.9%) and PST (71.8%). Both groups combined showed a significant improvement over the previous 6 months (71.0% vs. 62.5%; P = 0.04). Changes in time within the therapeutic range in individual patients (+5.86) also showed a significant difference. The quality of warfarin control in both PST and PSM may be superior to that achieved by conventional management in a specialised hospital anticoagulation clinic.