Confluent Thalamic Hyperintensities in CADASIL

Background: CADASIL is responsible for diffuse hyperintensities in the white matter on FLAIR images. These lesions are often associated with focal lesions in the basal ganglia such as lacunar infarctions. The prevalence and significance of diffuse or confluent thalamic hyperintensities (CTH) remain unknown. Methods: The frequency of hyperintensities on FLAIR images in the thalamus was assessed in 147 CADASIL patients, and signal abnormalities on both FLAIR and T(1)-weighted images were categorized as focal/punctuate or diffuse/confluent by the same reader. The areas of increased diffusion were also analyzed on apparent diffusion coefficient maps. The association of CTH with vascular risk factors, the main clinical manifestations of the disease and MRI markers (brain parenchymal fraction, volume of white matter hyperintensities, volume of lacunar infarcts and number of microbleeds) was analyzed with generalized linear regression models. Results: CTH were detected in 12% of the CADASIL subjects in association with hypointensities on T(1)-weighted images. CTH corresponded to areas of increased diffusion apparent diffusion coefficient maps. CTH were found significantly associated with age and independently related to the volume of white matter hyperintensities but not to that of lacunar infarctions or to cerebral atrophy after adjustment for age and sex. No significant association was found between CTH and global cognitive performances. Conclusion: CTH are observed on FLAIR images in a sizeable proportion of CADASIL patients. They are mainly related to the extent of white matter hyperintensities and do not correlate with cognitive decline. Demyelination and/or loss of glial cells appear to be the most plausible cause of these confluent signal changes in the thalamus. Copyright (C) 2010 S. Karger AG, Base

Clustering and Kernel Density Estimation for Assessment of Measurable Residual Disease by Flow Cytometry

peer reviewedStandardization, data mining techniques, and comparison to normality are changing the landscape of multiparameter flow cytometry in clinical hematology. On the basis of these principles, a strategy was developed for measurable residual disease (MRD) assessment. Herein, suspicious cell clusters are first identified at diagnosis using a clustering algorithm. Subsequently, automated multidimensional spaces, named “Clouds”, are created around these clusters on the basis of density calculations. This step identifies the immunophenotypic pattern of the suspicious cell clusters. Thereafter, using reference samples, the “Abnormality Ratio” (AR) of each Cloud is calculated, and major malignant Clouds are retained, known as “Leukemic Clouds” (L-Clouds). In follow-up samples, MRD is identified when more cells fall into a patient’s L-Cloud compared to reference samples (AR concept). This workflow was applied on simulated data and real-life leukemia flow cytometry data. On simulated data, strong patient-dependent positive correlation (R2 = 1) was observed between the AR and spiked-in leukemia cells. On real patient data, AR kinetics was in line with the clinical evolution for five out of six patients. In conclusion, we present a convenient flow cytometry data analysis approach for the follow-up of hematological malignancies. Further evaluation and validation on more patient samples and different flow cytometry panels is required before implementation in clinical practice

Variability among commercial batches of normal pooled plasma in lupus anticoagulant testing

Lupus anticoagulant (LA) testing requires normal pooled plasma (NPP) in performing mixing studies and can be used for normalized ratios of clotting times (CTs). The aims were to demonstrate whether significant differences in clotting times between two batches of a same commercial NPP (CRYOcheck™) directly affect NPP-based cut-off values. Diluted Russell Viper venom time (DRVVT) and activated partial thromboplastin time (aPTT) were used for LA testing. Screening, mixing and confirm tests were performed with Stago® instruments and reagents. Two batches of commercial NPP (A1291 and A1301 from CRYOcheck™; frozen) were compared in the determination of cut-off values. Cut-off values were defined as 99th percentile values of 60 healthy donors and compared with Mann-Whitney U test. Cut-off values obtained with the two NPP batches were significantly different for DRVVT (screen normalized ratio: 1.09 vs. 1.24, screen mix: 41.9 s vs. 38.9 s; index of circulating anticoagulant: 5.0 vs. 8.4; all had p-value <.001). On the contrary, no significant differences were observed for aPTT (screen normalized ratio: 1.32 vs. 1.34; p-value = .4068, screen mix: 37.8 s vs. 38.1 s; p-value = .1153) except for index of circulating anticoagulant: 9.6 versus 10.4 (p-value <.05). This study demonstrates that differences between two commercial NPP batches produced by a same manufacturer influenced LA cut-off values used for mixing studies and normalized ratios. Adequate cut-off setting, taking into account NPP CTs, is important to provide accurate conclusion about the presence or absence of a LA and avoid potential clinical impact

Prothrombotic Hemostasis Disturbances in Patients with Severe COVID-19:Individual daily data

This data article accompanies the manuscript entitled: "Prothrombotic Disturbances of hemostasis of Patients with Severe COVID-19: a Prospective Longitudinal Observational Cohort Study" submitted to by the same authors. We report temporal changes of plasma levels of an extended set of laboratory parameters during the ICU stay of the 21 COVID-19 patients included in the monocentre cohort: CRP, platelet count, prothrombin time; Clauss fibrinogen and clotting factors II, V and VIII levels, D-dimers, antithrombin activity, protein C, free protein S, total and free tissue factor pathway inhibitor, PAI-1 levels, von Willebrand factor antigen and activity, ADAMTS-13 (plasma levels); and of two integrative tests of coagulation (thrombin generation with ST Genesia) and fibrinolysis (global fibrinolytic capacity - GFC). Regarding hemostasis, we used double-centrifuged frozen citrated plasma prospectively collected after daily performance of usual coagulation tests. Demographic and clinical characteristics of patients and thrombotic and hemorrhagic complications were also collected from patient's electronic medical reports

Evaluation of the Fully Automated HemosIL Acustar ADAMTS13 Activity Assay.

ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13) is responsible for the proteolysis of ultra-large von Willebrand factor (VWF) multimers into smaller multimers.[1] Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) caused by severe ADAMTS13 deficiency (activity < 10%) leading to the formation of platelet-rich microthrombi within small arterioles responsible for the destruction of platelets and erythrocytes. [...

Dosage des D-dimères : variables pré-analytiques, analytiques, post-analytiques et applications cliniques

Les D-dimères comprennent l’ensemble des produits de dégradation de la fibrine stabilisée, induite par la plasmine. Ils peuvent donc être considérés comme un biomarqueur reflétant l’activation de la coagulation et de la fibrinolyse. Le dosage des D-dimères est couramment utilisé pour exclure la maladie thromboembolique veineuse, pour évaluer les risques de récidive d’une telle affection, et afin de définir la durée optimale d’un traitement anticoagulant. Cette adaptation de l’article original de Favresse et al. 1 est destinée à : (1) faire le point sur la définition des D-dimères ; (2) discuter des variables pré-analytiques affectant la mesure des D-dimères ; (3) examiner et comparer les performances de différents tests et de certaines variables post-analytiques et enfin de (4) discuter de l’utilisation clinique du dosage des D-dimères