Single-Nucleotide Polymorphisms in Thrombotic Thrombocytopenic Purpura: A Genetic Predisposition to Immune Thrombotic Thrombocytopenic Purpura.

There are two main classifications for thrombotic thrombocytopenic purpura (TTP): immune and hereditary. The majority of TTP cases are immune in nature and are due to inhibitor autoantibodies against ADAMTS13. Hereditary TTP is caused by biallelic pathogenic variants in the ADAMTS13 gene. Immune TTP is treated with therapeutic plasma exchange that both removes inhibitor autoantibodies and repletes deficient ADAMTS13. In hereditary TTP, the treatment is plasma infusion, as there are no inhibitor autoantibodies to remove. Our case report presents a 72-year-old male who experienced recurrent episodes of TTP and whose first episode was complicated by an occipital lobe stroke. Next-generation sequencing revealed three separate homozygous single-nucleotide polymorphisms (SNPs) in exon 1, exon 12, and exon 16 of the ADAMTS13 gene. Inhibitor autoantibody testing was negative in recurrent episodes, and treatment with plasma infusions for hereditary TTP led to relapses. The objective of our case report is to explore the combined effects of these SNPs on ADAMTS13 activity and antigen levels and question if these genetic variations can lower the threshold for an immune TTP episode. Future research is required to determine if lower-than-normal baseline ADAMTS13 activity levels can predispose a patient to TTP and the long-term complications associated with it.
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