Recommendations for the measurement of thrombin generation: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies.

Thrombin generation (TG) assay is an overall assay to assess the functionality of the hemostatic system and may be a useful tool in diagnosing patients with hyper- and hypocoagulability. Lack of standardization in performing the assays contributes largely to poor correlation between assays and study results. The current lack of standardization remains a major issue in the setting of TG, as illustrated in a recent survey of the ISTH/SSC indicating differences in pre-, analytical, and post-analytical factors among users. These factors may considerably affect the between-laboratory reproducibility of results. Based on the results of the survey and a current review of the literature, along with insights and strong consensus of key investigators in the field, we present guidance for measurement of TG in a clinical setting. Recommendations on blood drawing, handling, processing, and sample storage; reagent concentration and source; analytical conditions on dilution of samples and temperature; calibration and replicate testing; calculation and interpretation of results; and reference values are addressed to help in reducing interlaboratory variation. These recommendations aim at harmonization between methods and laboratories to support the application of TG in patient diagnosis and management.