Studies of the pathophysiology of acquired von Willebrand's disease in seven patients with lymphoproliferative disorders or benign monoclonal gammopathies

Abstract

In seven patients with acquired von Willebrand's disease (AvWD) associated with lymphoproliferative disorders or benign monoclonal gammopathies, the platelet contents of von Willebrand factor antigen and ristocetin cofactor (vWF:Ag and vWF:RiCof, respectively) were normal. All the multimers of vWF:Ag could be seen in the 1.6% SDS- agarose gel electrophoresis patterns of plasma and platelet lysates. Infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) augmented plasma levels of vWF:Ag and vWF:RiCof of all patients and corrected prolonged bleeding times (BT). However, compared with patients with congenital vWD type I and comparable degrees of baseline abnormalities treated in the same way, vWF:Ag and vWF:RiCof were increased less and cleared more rapidly from plasma and the BT remained normal for a shorter period of time. These studies provide evidence that these AvWD patients have qualitatively normal vWF in plasma, but at lower concentrations, that vWF in platelets is normal both qualitatively and quantitatively, and that cellular vWF can be rapidly released into plasma by DDAVP to correct the hemostatic abnormalities. However, vWF is removed rapidly from plasma, making the correction more transient than in congenital vWD type I.

Acquired von Willebrand's disease due to aberrant expression of platelet glycoprotein Ib by marginal zone lymphoma cells

“…Furthermore, monoclonal gammopathy (MG) is an essential component of other plasma cell proliferative disorders associated with AVWD, including multiple myeloma and Waldenström's macroglobulinaemia. Similarly, MG is often present in chronic lymphoproliferative disorders that have been associated with AVWD (Mannucci et al, 1984). However, the presence of MG has not always been evident in several of the haematological and nonhaematological disorders described in association with AVWD.…”

Mechanisms underlying acquired von Willebrand syndrome associated with an IgM paraprotein

“…In the multimeric analysis, all multimers were present. A lack of high molecular weight multimers as seen in type II vW disease is found in three quarters of the patients with acquired vWS, but a normal multimeric pattern has been described in patients with IgM paraprotein [11]. Notably, the triplet structure was blurred (Fig.…”

“…Adsorption of vW factor on cells or an increased clearance of vW factor from the plasma by non-immunological mechanisms has been described [3,4]. Most patients with lympho-or myeloproliferative disorders have IgG paraproteins, and data on patients with acquired vW syndrome and an IgM paraprotein are scarce [2,[9][10][11][12]. We report a patient with indolent B-cell lymphoma and an IgM j paraprotein, and present a complete diagnostic work-up of acquired vW syndrome due to complex formation of vW factor and the paraprotein.…”

Current issues facing coagulationists – meeting report1

“…In this subset of patients 87% present with bleeding but an antibody directed against FVIII/VWF is only detected in 12% of cases (overall an antibody was only detected in 16% of cases of AVWS). Detection of antibodies, usually IgG, is difficult but an ELISA based assay appears to be more sensitive than the standard inhibition study performed after incubation of test and normal plasma [35,36]. In AVWS associated with LPD the severity of the AVWS does not always correlate with the paraprotein level, if present, and in monoclonal gammopathy of uncertain significance there may be no satisfactory therapy for the underlying disorder.…”