Thrombotic microangiopathies

The term thrombotic microangiopathy (TMA) has been used to describe multiple disease entities characterized by endothelial injury, thrombus formation, and resultant microangiopathic hemolytic anemia (Coomb’s negative anemia with schistocytes in the peripheral smear), thrombocytopenia, and organ dysfunction (Table 1). The disease entities associated with TMA produce indistinguishable histologic findings and include the hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenia purpura (TTP) (Table 2). Microangiopathic hemolytic anemia results from partial occlusion of small vessels that causes mechanical trauma to the red cells. Platelet consumption at these sites leads to thrombocytopenia. Organ dysfunction may include major involvement of the brain and kidneys. Levels of free hemoglobin and lactate dehydrogenase (LDH) are elevated, and levels of haptoglobin are reduced or absent. Clinical and laboratory features help to identify the individual diseases associated with TMA (see Table 2). All of these disorders have in common a dysregulation of the endothelial cell, which is central to the pathogenesis of this group of diseases. Pathologic findings in thrombotic microangiopathy All diseases associated with TMA are characterized by renal biopsy findings of endothelial injury and thrombus formation. Although not required to establish the diagnosis, the most characteristic pathologic finding is intravascular and intraglomerular fibrin thrombi. The pathologic findings primarily involve glo