Severe ADAMTS-13 deficiency without hemolysis as a cause of cryptogenic stroke: A single center case series

Cerebral Infarction due to Severe ADAMTS-13 Deficiency (CISAD) remains an underrecognized cause of cryptogenic stroke. Despite the absence of classic hematologic features, CISAD confers a risk of recurrent ischemic events if not promptly identified and treated. Increased clinical awareness is essential to prompt appropriate laboratory testing and reduce stroke recurrence.

We conducted a retrospective cohort study at Montefiore Medical Center to identify patients with ischemic stroke and severe ADAMTS-13 deficiency from January 2017 to June 2025. Of 235 screened patients, 197 had an acute ischemic stroke. 9 met final inclusion criteria for CISAD: confirmed ischemic stroke, severe ADAMTS-13 deficiency at index event, and absence of microangiopathic hemolytic anemia (MAHA). Clinical, hematologic, and imaging characteristics were analyzed descriptively in the final cohort.

Of 9 patients, 7 were female. Mean age was 51.3 years. Platelet counts were normal in 6 of 9 cases. 4 of 9 patients had large vessel occlusions. 3 patients had multifocal infarcts. 8 of 9 patients met Embolic Stroke of Undetermined Source (ESUS) criteria before ADAMTS-13 testing. 1 had three ESUS events before ADAMTS-13 deficiency was identified. The remaining 6 patients had an established history of thrombotic thrombocytopenic purpura (TTP) and presented with recurrent strokes and severe ADAMTS-13 deficiency. 2 patients had multiple strokes with severe ADAMTS-13 deficiency. All patients were treated with steroids, therapeutic plasma-exchange (TPE), and/or Rituximab.

CISAD may present without hematologic abnormalities and should be considered as a rare cause of stroke. Early ADAMTS-13 activity and inhibitor testing in select patients may allow timely diagnosis, treatment, and prevention of recurrence.