title: Predicting response to plasma exchange in patients with thrombotic thrombocytopenic purpura with measurement of vWF-cleaving protease activity.
abstract: BACKGROUND
  Severe deficiency of vWF-cleaving protease (vWF-CPase) activity was recently found in patients with thrombotic thrombocytopenic purpura (TTP). Although the survival of patients with TTP has been dramatically improved with plasma exchange (PE), there are still many patients who are refractory to PE and immunosuppressive therapy.
  
  
  METHODS
  The activities of vWF-CPase and its inhibitor were measured in 27 patients with nonfamilial TTP and hemolytic-uremic syndrome (HUS) to examine the relationship between the clinical variables and vWF-CPase activity.
  
  
  RESULTS
  Eight of nine patients with HUS had more than 40 percent of vWF-CPase activity, whereas one had 28 percent of the normal level at the acute phase. Ten of 12 TTP patients with a good outcome had a severe deficiency of vWF-CPase activity and its inhibitor, whereas four of six patients with a poor outcome had a moderate deficiency of vWF-CPase activity along with a lack of the inhibitor. PE produced normalization of the vWF-CPase activity and neutralization of the inhibitor in TTP patients with a good outcome; however, some TTP patients with vWF-CPase inhibitor had relapsed and required an immunosuppressive therapy. The response to the combination therapy with PE and immunosuppressive treatment was poor in TTP patients without a severe deficiency of vWF-CPase activity.
  
  
  CONCLUSIONS
  Assays of vWF-CPase activity and its inhibitor may be useful for predicting the response to therapy and the outcome of patients with TTP. In some patients, nonfamilial TTP with a poor prognosis may not be caused by a constitutional or acquired deficiency of vWF-CPase with its inhibitor. Although PE and immunosuppressive therapy are effective in patients with nonfamilial TTP and a vWF-CPase inhibitor, other therapeutic modalities may be needed for nonfamilial TTP with unknown etiology.
authors.affiliation: Mie Red Cross Blood Center, Tsu City, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Mori
authors.forename: Hideo
authors.initials: H
authors.lastname: Wada
authors.forename: Esteban C
authors.initials: EC
authors.lastname: Gabazza
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Minami
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nobori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagi
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ishizashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood / Q000201:enzymology / Q000209:etiology / Q000628:therapy*; D015415:Biomarkers; D003131:Combined Modality Therapy; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000097:blood / Q000172:deficiency* / Q000276:immunology; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D010951:Plasma Exchange; D011379:Prognosis; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000188:drug therapy / Q000201:enzymology / Q000628:therapy*; D012008:Recurrence; D012189:Retrospective Studies; D012720:Severity of Illness Index; D017211:Treatment Failure; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D007166:Immunosuppressive Agents; D014841:von Willebrand Factor; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human; D008775:Methylprednisolone