Abstract
Thrombotic microangiopathies (TMAs) encompass a diverse group of syndromes marked by microvascular thrombosis, thrombocytopenia, and organ injury, primarily affecting the kidneys and central nervous system. While the etiologies differ-ranging from genetic mutations to infectious and autoimmune triggers-a unifying pathogenic mechanism is endothelial dysfunction. Recent advances have illuminated the pivotal role of cytokine dysregulation in initiating and sustaining this vascular injury. The release of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 creates a state of sustained endothelial activation that promotes leukocyte adhesion, vascular permeability, and a prothrombotic surface phenotype. In various TMA subtypes, the cytokine response acts as both a trigger and an amplifier of disease progression. In atypical hemolytic uremic syndrome (aHUS), cytokines are upregulated secondary to complement dysregulation, while in thrombotic thrombocytopenic purpura (TTP), inflammation may lower ADAMTS13 activity and potentiate thrombosis. Secondary TMAs, including those associated with autoimmune disease, pregnancy, and transplantation, often exhibit pronounced cytokine profiles that directly correlate with endothelial injury and clinical severity. These overlapping inflammatory signatures underscore the need to view TMAs not only through a hematologic or immunologic lens but also within the context of vascular inflammation.