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Objectives: Reliable diagnosis of heparin‐induced thrombocytopenia and thrombosis (HIT) is mandatory for patient management, yet prompt determination of pathogenic antibodies remains an unmet clinical challenge. Common immunoassays carry inherent limitations and functional assays which detect antibody‐mediated platelet activation are not usually readily available to routine laboratories, especially the serotonin release assay (SRA), being technically demanding, time consuming, and requires high level expertise. To overcome some of these limitations, we have developed a practical functional flow cytometric assay (FCA) for routine clinical use. Methods: A simple FCA is described which avoids platelet manipulation, is highly specific and sensitive compared with SRA, and provides rapid results. Results: Of the 650 consecutive samples, from HIT‐suspected patients, 99 (15.3%) were positive by the PaGIA Heparin/PF4 immunoassay and 31 (4.8%) by FCA. Average platelet activation was 11‐fold higher in PaGIA+/FCA+ vs PaGIA−/FCA− samples. Of 21 SRA‐positive samples, 19 were FCA‐positive (relative sensitivity 90.5%), and of 42 SRA‐negative samples, 40 were FCA‐negative (relative specificity 95.2%). The FCA showed significantly higher correlation with the clinical presentation of HIT (4Ts score) performed on 182 patients, compared with PaGIA Heparin/PF4 (ROC‐plot analysis, AUC 0.93 vs 0.63, P < 0.001). At a 92% sensitivity, the assay specificity was 96%. Conclusions: The present FCA is practical for routine testing, providing prompt reliable results for initial diagnosis and confirmation, to effectively assist in HIT patient management. [ABSTRACT FROM AUTHOR]

The front cover image is based on the Original Article* I Pathogenic heparin-induced thrombocytopenia and thrombosis (HIT) antibodies determined by rapid functional flow cytometry i by Michal Cipok** et al., https://doi.org/10.1111/ejh.13277 GRAPH. [Extracted from the article]

Abstract: Multiple myeloma is characterized by the malignant growth of immunoglobulin producing plasma cells, predominantly in the bone marrow. The effects of primary human mesenchymal stromal cells on the differentiation phenotype of multiple myeloma cells were studied by co-culture experiments. The incubation of multiple myeloma cells with bone marrow-derived mesenchymal stromal cells resulted in significant reduction of the expression of the predominant plasma cell differentiation markers CD38 and CD138, and cell surface immunoglobulin light chain. While the down-regulation of CD138 by stromal cells was completely dependent on their adhesive interactions with the multiple myeloma cells, interleukin-6 induced specific down-regulation of CD38. Mesenchymal stromal cells or their conditioned media inhibited the growth of multiple myeloma cell line, thereby reducing the overall amounts of secreted light chains. Analysis of primary multiple myeloma bone marrow samples reveled that the expression of CD38 on multiple myeloma cells was not affected by adhesive interactions. The ex vivo propagation of primary multiple myeloma cells resulted in significant increase in their differentiation markers. Overall, the data indicate that the bone marrow-derived mesenchymal stromal cells revert multiple myeloma cells to less differentiated phenotype by the combined activities of adhesive interactions and interleukin-6. [Copyright &y& Elsevier]