Immune-Mediated Etiology of Acquired von Willebrand Syndrome in Systemic Lupus Erythematosus and in Benign Monoclonal Gammopathy: Therapeutic Implications

Jan J. Michiels; Zwi Berneman; Alain Gadisseur; Marc van der Planken; Wilfried Schroyens; Ulrich Budde; Huub H. D. M. van Vliet

doi:10.1055/s-2006-949663

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2006; 32(6): 577-588
DOI: 10.1055/s-2006-949663

Immune-Mediated Etiology of Acquired von Willebrand Syndrome in Systemic Lupus Erythematosus and in Benign Monoclonal Gammopathy: Therapeutic Implications

Jan J. Michiels¹ ^, ⁵ , Zwi Berneman¹ , Alain Gadisseur¹ , Marc van der Planken² , Wilfried Schroyens¹ , Ulrich Budde³ , Huub H.D.M van Vliet⁴

¹Hemostasis Thrombosis Research, Department of Hematology, University Hospital Antwerp, Belgium
²Laboratory of Hemostasis and Hematology, Department of Clinical Biology, University Hospital Antwerp, Belgium
³Coagulation Laboratory, Hamburg, Germany
⁴Hemostasis and Thrombosis Research, Erasmus Medical Center, Rotterdam
⁵Goodheart Institute, Hemostasis Thrombosis and Vascular Research Center, Rotterdam, The Netherlands

Abstract

ABSTRACT

The most common nonimmune etiology of acquired von Willebrand syndrome (AvWS) includes hypothyroidism, Wilms' tumor, thrombocythemia, or congenital heart defects, and the use of various drugs. AvWS type 1 in patients with hypothyroidism is due to decreased Willebrand factor (vWF) synthesis and is reversible by treatment with thyroxin. AvWS type 1 or 3 in children with Wilms' tumor disappears after successful chemotherapy or tumor resection but the mechanism of the vWF deficiency is unknown. The AvWS type 2 in patients with thrombocythemia of various myeloproliferative disorders is caused by increased proteolysis of large vWF multimers at increasing platelet counts to above 1000 × 10⁹/L. Reduction of platelet counts to normal results in correction of the vWF parameters together with disappearance of the bleeding tendency. Type 2-like AvWS in children with congenital heart valve defects is caused by shear stress-induced proteolysis of large vWF multimers and is reversible after surgical correction. AvWS associated with the use of drugs disappears after discontinuation of the causative agent. Immune-mediated AvWS is associated with either systemic lupus erythematosus (SLE) or immunoglobulin G (IgG) benign monoclonal gammopathy (BMG), and usually shows a type 2 vWF deficiency. Using a simple enzyme-linked immunosorbent assay, an IgG antibody against vWF is detectable in AvWS associated with SLE and IgG BMG. The IgG-autoantibody-factor (F) vWF/VIII complex is rapidly cleared from the circulation, which explains the combined FVIII:coagulant activity (C) and vWF deficiency and the poor responses of FVIII:C and vWF parameters to intravenous desmopressin acetate and vWF/FVIII concentrates. A transient correction of both FVIII:C and vWF parameters to normal for a few weeks after high-dose intravenous immunoglobulin is seen in AvWS associated with SLE and IgG BMG. AvWS associated with SLE uniformly shows a curative response to corticosteroids. AvWS associated with IgG BMG does not respond to corticosteroids, immune suppression, or chemotherapy. AvWS associated with IgM BMG is rare and does not respond to any conventional treatment.

KEYWORDS

Acquired von Willebrand syndrome (AvWS) - systemic lupus erythematosus - monoclonal gammopathy - hypothyroidism - Wilms' tumor - thrombocythemia - diagnosis - treatment

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References

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Jan J MichielsM.D. Ph.D.

Hemostasis & Thrombosis Research, Dept. of Hematology

University of Antwerp, Antwerp, Belgium

Email: postbus@goodheartcenter.demon.nl