Thrombosis, Microangiopathies, and Inflammation.
Thrombotic microangiopathy (TMA) is characterized by the presence of microangiopathic hemolytic anemia and thrombocytopenia. There are several disorders with varied etiopathogenesis, both genetic and acquired, that result in TMA. The neutrophils play an important role in inflammation and thrombosis through the formation of neutrophil extracellular traps (NETs). NETs are formed in response to a variety of stimuli including infections, chemical factors, and platelet activation. The classic TMA, thrombotic thrombocytopenic purpura (TTP) is caused by a severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type-I motif, member 13), mostly acquired due to autoantibodies, whereas atypical hemolytic uremic syndrome (aHUS) is mostly attributed to genetic defects in complement pathway regulatory proteins. The management of these well-known disorders has evolved over the last decade. Similarly, there is also better understanding of diverse and unusual clinical presentations of both of these conditions. Since there are many other causes of TMAs, which may mimic some of the clinical features of TTP or aHUS, it is essential to thoroughly investigate each patient so that appropriate therapy can be offered. This review focuses on some important developments in understanding of etiopathogenesis, diagnosis, and treatment of more commonly encountered TMAs.
Division of Transfusion Medicine and Hemostasis, Department of Pathology, UT Southwestern Medical Center, Dallas, Texas.
Karen
K
Matevosyan
Division of Transfusion Medicine and Hemostasis, Department of Pathology, UT Southwestern Medical Center, Dallas, Texas.
Ravi
R
Sarode
D051722:ADAM Proteins / Q000172:deficiency / Q000235:genetics; D000071120:ADAMTS13 Protein; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000150:complications; D004211:Disseminated Intravascular Coagulation / Q000209:etiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D065206:Extracellular Traps / Q000276:immunology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology; D009504:Neutrophils / Q000276:immunology; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D012772:Shock, Septic / Q000209:etiology; D061905:Single-Domain Antibodies; D057049:Thrombotic Microangiopathies / Q000097:blood* / Q000139:chemically induced / Q000150:complications / Q000276:immunology / Q000628:therapy
D007166:Immunosuppressive Agents; D061905:Single-Domain Antibodies; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human