Innovative Molecular Testing Strategies for Adjunctive Investigations in Hemostasis and Thrombosis

Abstract

Clinicians and scientists in the fields of hemostasis and thrombosis have been among those first to integrate new molecular strategies for the purpose of enhancing disease diagnosis and treatment. The molecular diagnosis and introduction of gene therapy approaches for hemophilia are obvious examples of this tendency. In this review, the authors summarize information concerning three molecular technologies that have reached various stages of translational potential for their incorporation into the clinical management of disorders of hemostasis. Chromatin conformation assays are now being used to capture structural knowledge of long-range genomic interactions that can alter patterns of gene expression and contribute to quantitative trait pathogenesis. Liquid biopsies in various forms are providing opportunities for early cancer detection, and in the context of tumor-educated platelets, as described here, can also characterize tumor type and the extent of tumor progression. This technology is already being trialed in patients with unprovoked venous thrombosis to assess the potential for occult malignancies. Lastly, advances in single cell transcriptome analysis, provide opportunities to definitively determine molecular events in rare cells, such as antigen-specific regulatory T cells, within the context of heterogeneous cell populations.

Understanding the extent of the diagnostic potential of coagulation factors

“…Thus, comparatively, phenotypic tests have far greater utility, and are more broadly applied. This situation may change in the future, with evolution of improved molecular methods and nextgeneration tools [7][8][9][10]. As an example of the current state of play, one FVIII gene (designated F8) database currently lists 2611 unique variants (https://databases.lovd.nl/shared/ variants/F8/unique), and the associated FIX gene (F9) database currently lists 1112 unique variants (https://databases.…”

“…Nevertheless, molecular testing tools in the area of hemostasis are ever improving. Next-generation sequencing and adjunct tools continue to be developed for hemostasis applications [7][8][9][10][11][12], and these will expectedly revolutionize diagnostic strategies for bleeding disorders. However, for the time being, at least, phenotypic testing remains the current diagnostic strategy for most bleeding disorders [1][2][3][4][5]15].…”

Molecular and Genetic Testing in Thrombosis and Hemostasis

“…The final review is written by Ghorbanpour and Lillicrap. 21 This paper closes the issue and steps away from technologies that are currently employed in the clinic and discusses exciting translational methods of chromatin conformation assays, liquid biopsies, and single-cell transcriptome analysis. Crucial elements in generating patientspecific genetic data are determining the significance of the generated molecular detail and adjudicating the influence (if any) from other intra or intergenic variants on the clinical phenotype.…”