Pathogenesis of thrombotic microangiopathies.
Profound thrombocytopenia and microangiopathic hemolytic anemia characterize thrombotic microangiopathy, which includes two major disorders: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). TTP has at least three types: congenital or familial, idiopathic, and nonidiopathic. The congenital and idiopathic TTP syndromes are caused primarily by deficiency of ADAMTS13, owing to mutations in the ADAMTS13 gene or autoantibodies that inhibit ADAMTS13 activity. HUS is similar to TTP, but is associated with acute renal failure. Diarrhea-associated HUS accounts for more than 90% of cases and is usually caused by infection with Shiga-toxin-producing Escherichia coli (O157:H7). Diarrhea-negative HUS is associated with complement dysregulation in up to 50% of cases, caused by mutations in complement factor H, membrane cofactor protein, factor I or factor B, or by autoantibodies against factor H. The incomplete penetrance of mutations in either ADAMTS13 or complement regulatory genes suggests that precipitating events or triggers may be required to cause thrombotic microangiopathy in many patients.
Zheng
X Long
XL
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. zheng@email.chop.edu
Sadler
J Evan
JE
D051722:ADAM Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000071120:ADAMTS13 Protein; D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D003967:Diarrhea / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008833:Microcirculation / Q000473:pathology; D017354:Point Mutation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D014841:von Willebrand Factor / Q000378:metabolism
D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human