Inherited platelet function disorders are rare hemorrhagic diseases. The gold standard for their exploration is optical aggregometry; however, investigations by flow cytometry (FCM) are being increasingly used. In this review, the physiology of platelets is first recalled, setting the stage for the compartments of platelets that can be apprehended by specific and appropriate labeling. As this requires some preanalytical precautions and specific analytical settings, a second part focuses on these characteristic aspects, based on literature and on the authors' experience in the field, for qualitative or quantitative explorations. Membrane labeling with antibodies to CD42a or CD41, respectively, useful to assess the genetic-related defects of Glanzmann thrombocytopenia and Bernard Soulier syndrome are then described. Platelet degranulation disorders are detailed in the next section, as they can be explored, upon platelet activation, by measuring the expression of surface P-Selectin (CD62P) or CD63. Mepacrin uptake and release after activation is another test allowing to explore the function of dense granules. Finally, the flip-flop anomaly related to Scott syndrome is depicted. Tables summarizing possible FCM assays, and characteristic histograms are provided as reference for flow laboratories interested in developing platelet exploration.
BACKGROUND: Despite their usefulness in perioperative and acute care settings, factor-Xa inhibitor-specific assays are scarcely available, contrary to heparin anti-Xa assay. We assessed whether the heparin anti-Xa assay can (1) be used as a screening test to rule out apixaban, rivaroxaban, fondaparinux, and danaparoid levels that contraindicate invasive procedures according to current guidelines (>30 ng·mL−1, >30 ng·mL−1, >0.1 µg·mL−1, and >0.1 IU·mL−1, respectively), (2) quantify the anticoagulant level if found significant, that is, if it exceeded the abovementioned threshold. METHODS: In the derivation cohort then in the validation cohort, via receiver operating characteristics (ROC) curve analysis, we evaluated the ability of heparin anti-Xa assay to detect levels of factor-Xa inhibitors above or below the abovementioned safety thresholds recommended for an invasive procedure (screening test). Among samples with relevant levels of factor-Xa inhibitor, we determined the conversion factor linking the measured level and heparin anti-Xa activity in a derivation cohort. In a validation cohort, the estimated level of each factor-Xa inhibitor was thus inferred from heparin anti-Xa activity. The agreement between measured and estimated levels of factor-Xa inhibitors was assessed. RESULTS: Among 989 (355 patients) and 756 blood samples (420 patients) in the derivation and validation cohort, there was a strong linear relationship between heparin anti-Xa activities and factor-Xa inhibitors measured level (r = 0.99 [95% confidence interval {CI}, 0.99–0.99]). In the derivation cohort, heparin anti-Xa activity ≤0.2, ≤0.3, <0.1, <0.1 IU·mL−1 reliably ruled out a relevant level of apixaban, rivaroxaban, fondaparinux, and danaparoid, respectively (area under the ROC curve ≥0.99). In the validation cohort, these cutoffs yielded excellent classification accuracy (≥96%). If this screening test indicated relevant level of factor-Xa inhibitor, estimated and measured levels closely agreed (Lin’s correlation coefficient close to its maximal value: 95% CI, 0.99–0.99). More than 96% of the estimated levels fell into the predefined range of acceptability (ie, 80%–120% of the measured level). CONCLUSIONS: A unique simple test already widely used to assay heparin was also useful for quantifying these 4 other anticoagulants. Both clinical and economic impacts of these findings should be assessed in a specific study.
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