Beth Israel Deaconess Medical Center (BIDMC) has received a USD 1.63 million NIH R01 grant from the National Heart, Lung, and Blood Institute to investigate ADAMTS13 deficiency across a spectrum of thrombotic disorders — research that carries direct clinical relevance following the FDA approval of recombinant ADAMTS13 (Takeda's Adzynma) for immune thrombotic thrombocytopenic purpura (iTTP).
The award funds two parallel lines of inquiry. The first leverages the Harvard TMA Research Collaborative (HTRC), a large single-center iTTP registry assembled by BIDMC investigators, to build predictive models for relapse, refractoriness, and mortality in iTTP patients. The grant also supports the first genome-wide association and admixture mapping studies in iTTP, aimed at identifying germline variants that may explain the disproportionate disease burden observed in certain populations. The second line extends beyond iTTP: using genomic and proteomic data from approximately 800,000 individuals in the UK Biobank and NIH All of Us datasets, the team will examine whether moderate ADAMTS13 deficiency — activity between 10% and 70%, versus the severe deficiency that defines iTTP — contributes to common macrovascular events including stroke, myocardial infarction, peripheral artery disease, and venous thromboembolism.
ADAMTS13 cleaves ultra-large von Willebrand factor multimers, preventing pathological platelet aggregation in the microvasculature. In iTTP, severe enzyme deficiency drives diffuse microvascular thrombosis and end-organ damage. The hypothesis that moderate deficiency may also elevate risk for common thrombotic events remains unproven at population scale — making the large multiomic analysis a central scientific contribution of this award.