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Endothelial cell injury accompanied by microvascular thrombosis (thrombotic microangiopathy or TMA) is associated with thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, cancer, autoimmune diseases, and a variety of drugs, including interferons. Whether interferons directly injure the endothelium or require other mediators to induce disease has been uncertain.
To determine whether recombinant type I interferons are a direct cause of TMA, investigators studied patients with multiple sclerosis receiving treatment with interferon-β and conducted experiments using a mouse model of interferon toxicity.
The findings were as follows:
Patients who developed TMA received higher weight-adjusted doses of interferon than those who did not dev…