The 2024 Guidelines for the Primary Prevention of Stroke, recently updated by the American Heart Association and the American Stroke Association, serve as an essential resource for clinicians aiming to reduce the growing impact of cerebrovascular disease. These guidelines emphasize modifiable risk factors and population-specific considerations, covering a range of cardiovascular conditions, including hypertension, diabetes, atherosclerotic disease, and genetic predispositions to stroke. However, a notable omission in these guidelines is the absence of specific recommendations for patients with thrombotic thrombocytopenic purpura. Indeed, these patients are particularly susceptible to stroke, which can be the sole manifestation of the disease. Given the established association between thrombotic thrombocytopenic purpura and ischemic stroke and the effectiveness of preventive interventions, future guidelines should include specific recommendations for patients with thrombotic thrombocytopenic purpura to avert thrombotic events, including stroke. In that regard, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) activity measurement should be considered in the workup of cryptogenic stroke.