A 17-year old woman (patient 1) was found to have severe bleeding as the initial manifestation of systemic lupus erythematosus. Profound deficiencies of factor VIII coagulation activity (10%), von Willebrand factor (vWF) antigen (<10%), and rlstocetin cofactor (<1%), and a disproportionate loss of large molecular weight multimers of vWF were observed. An antibody to vWF was suspected, and an enzyme-linked immunoadsorbent assay (ELISA) was devised to detect and quantify such antibody. The ELISA measured the binding of anti-vWF antibody from sample plasma to surfacebound vWF antigen. Binding was detected by a conjugate of alkaline phosphatase with affinity-purified anti-human Immunoglobulin G, A, or M and a chromogenic substrate for alkaline phosphatase. Controls included plasma from normal subjects, from patients with von Willebrand's disease, and from a patient (patient 2) with type III von Willebrand's disease who had developed an inhibitor to vWF. Analysis of our patient's plasma revealed immunoglobulin G, A, and M anti-vWF antibodies. Preincubation of the plasma from patient 1 and patient 2 with pure vWF antigen completely inhibited antibody binding, confirming antibody specificity. These antibodies were quantitatively titered by determining the volume ratio of normal pooled plasma (a source of vWF antigen) to test plasma required to inhibit 50% of the antibody binding to immobilized vWF antigen. The value was 0.8 ± 0.3 (mean ± SD of three determinations) for the immunoglobulin G of our patient as compared with 15.6 ± 2.9 for the immunoglobulin G of patient 2. The titers of the immunoglobulin A and M were less than 0.05. Increases in factor VIII coagulant activity, vWF antigen, and ristocetin cofactor and control of hemorrhage could be translently achieved by use of intravenous and intranasal desmopressin and the factor VIII concentrate Humate-P. Treatment with prednisone over an 8-month period led to a cessation of bleeding, restored normal levels of vWF and multimers, and decreased antibody titers. This study documented a case of acquired von Willebrand's disease caused by systemic lupus erythematosus and the development of an ELISA to detect and quantitate the presence of anti-von Willebrand factor antibody.
|Original language||English (US)|
|Number of pages||7|
|Journal||The Journal of laboratory and clinical medicine|
|State||Published - Mar 1993|
ASJC Scopus subject areas
- Pathology and Forensic Medicine