Flow cytometry analyses from the peripheral blood revealed an enhanced cytotoxic behavior through circulating CD8<sup>+</sup>GzmB<sup>+</sup> T, CD4<sup>+</sup>GzmB<sup>+</sup> T lymphocytes, and residual CD19<sup>+</sup>GzmB<sup>+</sup> B cells.<h4>Conclusions</h4>Fatal VTE may be a rare outcome, particularly in patients exhibiting SM, and may share poorly understood immunological mechanisms with AQP4-positive NMOSD severity. Here, AQP4 is linked to systemic mastocytosis.