How I treat thrombotic microangiopathy in the era of rapid genomics.

Thrombotic microangiopathy (TMA) encompasses various genetically driven diseases. The emergence of ultra-fast genomic sequencing has recently opened up new avenues of research for genetic investigations in the setting of intensive care units. TMA is likely to be a suitable focus for fast-track genomic sequencing. By establishing an expeditious molecular diagnosis of patients with complement-dependent hemolytic uremic syndrome, fast-track genomic sequencing allows for the timely implementation or withdrawal of anti-C5 treatment while averting unnecessary, costly, and potentially harmful therapy in patients testing negative. Furthermore, genomics has the potential to reshape the taxonomic classification of TMA thanks to comprehensive genomic analysis. The most significant results arising from such analysis can be categorized as i) new descriptions of genetic diseases previously not recognized as associated with TMA, and ii) an enrichment of the phenotypic spectrum of diseases traditionally related to TMA. The latter draws on the concept of retrophenotyping, whereby genomic investigation precedes full clinical description. By taking precedence over a phenotypic approach, an unbiased genomic-focused analysis maximizes the chances of discovering new descriptions related to a given variant. Presented here are four cases of TMA which highlight these issues and substantiate the promise of fast-track genomic sequencing.