Thrombotic Microangiopathies Definition: Thrombotic microangiopathies (TMAs) are a group of disorders characterized by the formation of small blood clots (thrombi) in the microvasculature, leading to widespread organ damage. Two prominent TMAs are Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic Uremic Syndrome (HUS). Both conditions share overlapping features but have distinct etiologies and clinical presentations. Thrombotic Thrombocytopenic Purpura (TTP) Pathophysiology: TTP is a life-threatening disorder characterized by the pentad of symptoms: thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms, renal dysfunction, and fever. The key pathological feature of TTP is the severe deficiency of the von Willebrand factor-cleaving enzyme, ADAMTS13. This enzyme is responsible for degrading large von Willebrand factor multimers that cause excessive platelet aggregation. A deficiency or inhibition of ADAMTS13 leads to the formation of these large multimers, resulting in microthrombi that damage the endothelium and cause systemic platelet consumption. Clinical Presentation:  Thrombocytopenia: Low platelet count leading to purpura, petechiae, and bleeding tendencies.  Hemolytic Anemia: Due to the destruction of red blood cells by the microthrombi, characterized by elevated lactate dehydrogenase (LDH), low haptoglobin, and elevated indirect bilirubin.  Neurological Symptoms: Including headache, confusion, seizures, or stroke.  Renal Dysfunction: Ranges from mild elevation of creatinine to acute renal failure.  Fever: May occur but is not always present. Diagnosis:  Clinical Criteria: Diagnosis is based on clinical features and laboratory findings.  ADAMTS13 Activity: Measurement of ADAMTS13 enzyme activity and inhibitor levels. Severe deficiency of ADAMTS13 supports the diagnosis of TTP.  Blood Smear: Reveals fragmented red blood cells (schistocytes) indicative of hemolytic anemia. Management:  Plasma Exchange (Plasmapheresis): The primary treatment to remove inhibitory antibodies and replenish functional ADAMTS13 enzyme.  Corticosteroids: Often used to suppress immune activity.  Rituximab: May be used in cases associated with severe autoimmune etiology.