Ras-associated autoimmune leukoproliferative disorder associated with immune thrombotic thrombocytopenic purpura

Background

Ras-associated autoimmune leukoproliferative disorder (RALD) is a rare, nonmalignant condition characterized by monocytosis, lymphoproliferation, and autoimmunity, driven by KRAS or NRAS variants. Immune thrombotic thrombocytopenic purpura (iTTP) results from autoantibodies against ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Key clinical question: Can RALD co-occur with iTTP, and how can it be diagnosed? Clinical approach: A patient presenting with neutropenia, monocytosis, and thrombocytopenia was initially diagnosed with chronic myelomonocytic leukemia. She later developed splenomegaly, lymphadenopathy, and iTTP. Reevaluation identified a somatic KRAS G12A variant in peripheral blood, prompting a diagnosis of RALD. Flow cytometry demonstrated immunophenotypic changes involving B cells, T cells, and monocytes. The patient had four ADAMTS13 relapses, responsive to rituximab.