Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura.

Authors

Tsai HM, Lian EC 

Institution

Division of Hematology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY 10467, USA.

Source

N Engl J Med 1998 Nov 26; 339(22) :1585-94.

Abstract

BACKGROUND
Thrombotic thrombocytopenic purpura is a potentially fatal disease characterized by widespread platelet thrombi in the microcirculation. In the normal circulation, von Willebrand factor is cleaved by a plasma protease. We explored the hypothesis that a deficiency of this protease predisposes patients with thrombotic thrombocytopenic purpura to platelet thrombosis.
METHODS
We studied the activity of von Willebrand factor-cleaving protease and sought inhibitors of this protease in plasma from patients with acute thrombotic thrombocytopenic purpura, patients with other diseases, and normal control subjects. We also investigated the effect of shear stress on the ristocetin cofactor activity of purified von Willebrand factor in the cryosupernatant fraction of the plasma samples.
RESULTS
Thirty-nine samples of plasma from 37 patients with acute thrombotic thrombocytopenic purpura had severe deficiency of von Willebrand factor-cleaving protease. No deficiency was detected in 16 samples of plasma from patients with thrombotic thrombocytopenic purpura in remission or in 74 plasma samples from normal subjects, randomly selected hospitalized patients or outpatients, or patients with hemolysis, thrombocytopenia, or thrombosis from other causes. Inhibitory activity against the protease was detected in 26 of the 39 plasma samples (67 percent) obtained during the acute phase of the disease. The inhibitors were IgG antibodies. Shear stress increased the ristocetin cofactor activity of von Willebrand factor in the cryosupernatant of plasma samples obtained during the acute phase, but decreased the activity in cryosupernatant of plasma from normal subjects.
CONCLUSIONS
Inhibitory antibodies against von Willebrand factor-cleaving protease occur in patients with acute thrombotic thrombocytopenic purpura. A deficiency of this protease is likely to have a critical role in the pathogenesis of platelet thrombosis in this disease.

Mesh

ADAM Proteins
Acute Disease
Autoantibodies
Case-Control Studies
Humans
Immunoglobulin G
Metalloendopeptidases
Purpura, Thrombotic Thrombocytopenic
Reference Values
Rheology
von Willebrand Factor

Language

eng

Pub Type(s)

Journal Article

PubMed ID

9828246