血液疾患と輸血ジャーナル

概要

The Many Faces of Thrombotic Microangiopathies

Granfortuna J

The thrombotic microangiopathies are a complex group of disorders that typically present with a schistocytic hemolytic anemia and associated thrombocytopenia with ensuing microvascular occlusion leading to tissue ischemia and end organ damage. Central nervous system, renal, gastrointestinal and cardiac microcirculations are frequent targets. Signs and symptoms related to organ dysfunction may evolve over weeks to months and may not be present simultaneously. Lactic dehydrogenase enzyme elevation due to microvascular ischemia is frequently disproportionate to elevation of bilirubin or reticulocyte count. The major thrombotic microangiopathies include Thrombotic thrombocytopenic purpura, Disseminated intravascular coagulation/sepsis, and Hemolytic Uremic Syndrome. Hemolytic Uremic Syndrome may be further divided into “typical”, related to Shiga toxin, “atypical”, related to dysregulation or over-activation of Complement, and secondary, including disorders of pregnancy such as the Hepatic enzyme elevation low platelet syndrome or pre-eclampsia, certain other infections such as Streptococccus pneumonia, auto-immune disorders such as Sjogren’s syndrome, cancer, chemotherapy, or other medications, such as quinine and calcineurin inhibitors. These disorders can provoke direct microvascular damage and present as a thrombotic microangiopathy or act as a trigger for a microangiopathic syndrome in individuals with a genetic predisposition. The level of ADAM-TS 13, Von Willebrand Factor cleaving enzyme, is a key discriminator between Thrombotic thrombocytopenic purpura and HUS being severely reduced in Thrombotic thrombocytopenic purpura but not Hemolytic Uremic Syndrome. Plasma exchange with or without steroids is the mainstay of treatment for Thrombotic Thromobocytopenic Purpura. Anti C5 complement antibody therapy has evolved as an important treatment for atypical Hemolytic Uremic Syndrome. Although we have gained significant insight into the pathophysiology of many of these disorders, given the complex interplay between genetic factors, acquired factors, the roles of the humoral, cellular, and innate immune systems, the inflammatory response, and the coagulation system, thrombotic microangiopathies remain clinically challenging. This review will focus on a summary of our current knowledge with regard to diagnosis and treatment of Thrombotic thrombocytopenic purpura and Hemolytic Uremic Syndrome and how they relate to each other and the broader family of thrombotic microangiopathies. Three clinical cases will be used to illustrate key points.