Immune-mediated thrombotic thrombocytopenic purpura as a model of systemic microvascular dysfunction: moving from an acute to a chronic disorder

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening thrombotic microangiopathy. More and more studies clearly show a high prevalence of several adverse long-term health issues following recovery in these patients. Therefore, nowadays, the paradigm of iTTP as an acute episodical disease is quickly changing and should be considered a chronic disorder. The present review focuses on the 2 main long-term complications occurring during clinical remission in these patients (ie, cardiovascular and neurological complications). Our goal is to provide an updated overview of this topic, explaining the main related pathogenic mechanisms and highlighting how iTTP is emerging as a model not only of acute systemic microvascular dysfunction but also of chronic systemic microvascular dysfunction. The most accredited hypothesis supporting the chronicity of the disease is that, after recovery from an acute iTTP episode, a state of cumulative microvascular damage could persist and progress over time. However, the trajectory remains rather unpredictable, and there is still poor evidence on preclinical biomarkers able to identify those patients at higher risk of long-term cardiovascular and neurological complications, as well as drugs able to prevent chronic cardiac or brain organ damage. To date, there are no clear guidelines in this field, and clinical practice is quite heterogeneous across reference centers. A task force within the scientific community would be important for standardizing the most appropriate monitoring tools and preventive approaches to long-term complications in iTTP patients.