Hematological and Renal Involvement in Thrombotic Microangiopathies

Thrombotic microangiopathies (TMA) are life-threatening conditions associated with thrombocytopenia, microangiopathic hemolytic anemia and organ damage. TMA can be divided into three different syndromes: (1) Thrombotic thrombocytopenic purpura (TTP) occurs when the enzyme ADAMTS-13, which helps prevent blood clotting, does not function properly either due to a genetic deficit or the presence of antibodies that impair its function. The absence or insufficiency of ADAMTS-13 leads to uncontrolled binding of platelets to endothelial cells and the formation of blood clots in small blood vessels. (2) Hemolytic-uremic syndrome (HUS) comprehend a variety of patterns characterized by severe acute renal failure as well as low platelet counts and microangiopathic hemolytic anemia (MHA). Classic HUS is usually caused by enteropathogens such as E. coli and Shigella, which release toxins similar to Shiga toxin. Shiga toxin-producing E. coli (STEC)HUS is usually acquired by eating contaminated food. (3) Atypical or complement-mediated hemolytic uremic syndrome (HUS), characterized by thrombocytopenia, MHA and often acute kidney injury (AKI), can be attributed to dysregulation of the alternative pathway of the complement system. The main cause is often a pathogenic gene variation of a complement regulatory gene or, less commonly, autoantibodies specifically directed against complement components. TMA episodes are often triggered by specific events such as pregnancy, drug use, malignancies, organ transplants or infections and can occur at any stage of life. Hematological and renal involvement in the course of TMA are both characterized by a severe prognosis and life-threatening consequences. Complement dysregulation and multi-organ damage are associated with the most dangerous effects of this disease. For this reason, it is essential to understand the pathological mechanisms underlying these syndromes and prevent systemic complications and mortality in TMA patients.