Acquired von Willebrand's syndrome with IgM inhibitor against von Willebrand's factor.

Abstract

SUMMARY This report describes a patient without evident underlying disease, in whom an acquired von Willebrand's syndrome was discovered before surgery. Coagulation abnormalities included a borderline bleeding time, a low retention of platelets on glass beads, decreased levels of factor VIII procoagulant activity (VIII.), factor VIII-related antigen (VIfIAg), and ristocetin-induced agglutination cofactor (VIfIv,,). After cryoprecipitate infusion the patient did not have the expected rise and there was no secondary increment in Vmffi. The patient was treated with prednisone for three weeks without significant improvement in the laboratory findings. Spontaneous resolution was observed long after this therapy. The haemostatic abnormalities were attributable to the presence of an inhibitor directed against VIIIvWF. This inhibitor was found in the IgM fraction. Its autoimmune nature is probable although we failed to demonstrate any inhibitory effect of Fab obtained from the patient's purified IgM. Despite the lack of inhibitory effect against VIIIAHF and VIIIAg, the low levels of all three activities of the factor VIII complex could be explained by the short half-life of immune complexes between factor VIII and the inhibitor.

A new ELISA assay for diagnosis of acquired von Willebrand Syndrome

“…This study confirms that the plasma of some patients with AVWS, can react with an epitope of VWF (the active site or anon-functional site) coated on polystyrene plates. Both the IgG and the IgM isotypes could be detected, as in several previous studies [15][16][17][18]. The IgG isotype was detected in eight patients and the IgM isotype in five patients.…”

“…Identification of these antibodies with functional assay is cumbersome [13,14]. Both the IgG and the IgM isotypes could be detected, as in several previous studies [15][16][17][18]. Some authors recommend a pharmacokinetic analysis after infusion of VIII/VWF concentrate in order to demonstrate the acquired origin of the VWF defect [17].…”

Acquired von Willebrand syndrome: Features and management

“…Patients with lymphoproliferative disorders comprise the largest group among the various underlying diseases, including MGUS [3,37,40], multiple myeloma [3,4,19,20,[41][42][43], Waldenstro¨m macroglobulinemia [44,45], malignant lymphoma [3,4,21,44], and chronic lymphocytic leukemia [4,46]. AvWS appears to be more frequent in men than in women of advanced age [37].…”

“…These purified immunoglobulin fractions may inhibit the binding of vWF to platelets by binding to a specific recognition site on the vWF [49]. The second most common immunoglobulin fraction associated with AvWS is IgM [18,44], followed rarely by IgA [46].…”

Acquired von willebrand syndrome due to an inhibitor specific for von willebrand factor antigens

“…In view of the late clinical onset, absence of previous transfusion therapy, and negative family history for a bleeding disorder, her factor VIII abnormalities are most consistent with acquired von Willebrand syndrome. Acquired von Willebrand syndrome has been reported in 36 patients who had a variety of associated diseases including autoimmune disorders [6,11,13,, lymphoproliferative disorders [3,7,10,27,28], gammopathies [6,9,10,14,[28][29][30]421, tumors [6,3 1,321, hematologic malignancies [8,34-361, vascular abnormalities [4,37-391, hypersensitivity reaction [40], and diabetes mellitus 121. In four patients, no underlying disease process was noted [6,23,41].…”