Navigating the Nexus: Lenalidomide-Associated Thrombotic Thrombocytopenic Purpura

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy (TMA) marked by thrombocytopenia, microangiopathic hemolytic anemia, and microvascular thrombosis leading to end-organ damage. While TTP commonly results from hereditary or acquired ADAMTS13 deficiency, its association with lenalidomide is notably rare. The link between lenalidomide and TMA is unclear and requires more studies, given the high mortality risk associated with TTP. The underlying mechanism may involve immunomodulatory effects leading to ADAMTS13 inhibitory antibody formation. Herein, we present a case of a 56-year-old male with a history of multiple myeloma status post autologous stem cell transplant, on lenalidomide maintenance therapy for over five years, who presented with progressive weakness, jaundice, palpitations, and paraesthesia in his extremities. On arrival, the patient was afebrile and was neurologically intact except for the subjective paraesthesia. He was found to have critically low ADAMTS13 activity at <0.03 IU/mL and detectable ADAMTS13 inhibitors, with other findings of TTP, requiring discontinuation of lenalidomide, in addition to receiving treatment for this life-threatening TMA.