title: von Willebrand factor-cleaving protease (ADAMTS-13) activity determination in the diagnosis of thrombotic microangiopathies: the Swiss experience.
abstract: Severe deficiency of von Willebrand factor (VWF)-cleaving protease (ADAMTS-13) activity (<5% of normal) is a specific finding for acute idiopathic thrombotic thrombocytopenic purpura (TTP), a disorder that presents as thrombocytopenia, microangiopathic hemolytic anemia, and often organ dysfunction such as neurological disturbances or renal failure, and fever. Between January 2001 and July 2003, ADAMTS-13 activity was determined in plasma samples of 396 consecutive patients referred to our laboratory for diagnostic purposes. Plasma samples with ADAMTS-13 activity less than 5% were in addition tested for the presence of inhibitory antibodies. Patients were assigned to 10 predefined clinical categories according to information provided by the referring clinician: thrombotic microangiopathy (TMA) not further specified; neoplasia- or chemotherapy-associated TMA; TMA following hematopoietic stem cell transplantation; TMA with additional/alternative disorder; idiopathic TTP; hemolytic-uremic syndrome (HUS) not specified; HUS with diarrhea prodrome (D+HUS); atypical HUS; other hematological disorder; and no clinical information available. Severe ADAMTS-13 deficiency was found in 69 (17%) patients, including 42 with acquired idiopathic TTP, either at initial presentation or at relapse, 14 with confirmed or suspected hereditary TTP, 10 with TMA not further specified, two with neoplasia- or chemotherapy-associated TMA, and one in continued clinical remission 3.4 years after splenectomy for plasma-refractory TTP. Forty-three (62%) patients with ADAMTS-13 activity less than 5% displayed inhibitory antibodies. Severe ADAMTS-13 deficiency was found in 60% of patients diagnosed with acute idiopathic TTP, but in none of 130 patients diagnosed with HUS or in any of the 14 patients with hematopoietic stem cell transplantation-associated TMA. Thus, plasma ADAMTS-13 activity less than 5% does not identify all patients clinically diagnosed with TTP, and severe ADAMTS-13 deficiency is not invariably associated with clinical manifestations of microvascular platelet clumping.
authors.affiliation: Central Hematology Laboratory, Inselspital, University of Bern, Switzerland.
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Kremer Hovinga
authors.forename: Jan-Dirk
authors.initials: JD
authors.lastname: Studt
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Alberio
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lämmle
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000743:Anemia, Hemolytic / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D008666:Metalloendopeptidases / Q000097:blood / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D011480:Protease Inhibitors / Q000494:pharmacology; D013557:Switzerland / Q000453:epidemiology; D013927:Thrombosis / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology* / Q000235:genetics
chemical_list: D011480:Protease Inhibitors; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human