Recurrent Multi-territorial Ischemic Stroke As the Initial Presentation of Thrombotic Thrombocytopenic Purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare hypercoagulable disorder characterized by fever, acute hemolytic anemia, thrombocytopenia, neurologic deficits, and renal failure. Due to the rarity of TTP, the infrequency of a complete TTP pentad, variable and atypical presentations, and overlap with other thrombotic microangiopathy, diagnosis is difficult to achieve. Here, we describe a middle-aged patient with recurrent multi-territory strokes, with the development of thrombocytopenia occurring later in the course of her illness without fever, hemolytic anemia, or renal failure. Etiologies for prior history of ischemic stroke were confounded by the presence of intrinsic cerebral arteriopathy at the bilateral anterior cerebral artery, middle cerebral artery, and posterior cerebral artery territories attributed to accelerated atherosclerosis from concurrent tobacco smoking and marijuana abuse. Extensive workup also disclosed inter-atrial shunt (grade III patent foramen ovale), which was subsequently treated with device closure for presumed secondary stroke prevention. Due to the development of thrombocytopenia and recurrent multi-territory strokes, an ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) screen was ordered and was positive. The ADAMTS13 activity was <5%, while the ADAMTS13 inhibitor Bethesda titer was notably high (1.4, normal <0.4). For acute therapy, a three-day 1 mg/kg methylprednisolone was started, and a hematology service was consulted for co-management. The patient completed four rounds of plasmapheresis while receiving 90 mg of prednisone daily. She was then started on a regimen to complete four doses of weekly rituximab. The patient improved clinically during her stay, with noted improvements in platelet count and ADAMTS13 activity. In conclusion, thrombocytopenia may appear until later in the disease course with variant presentations of TTP. A low threshold to consider atypical etiologies when pursuing workup for cryptogenic stroke should be in mind when evaluating young adults with recurrent multi-territory ischemic stroke.