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We report the case of a man suffering from a monoclonal gammapathy with an acquired von Willebrand disease in a perioperative context. This pathology is rare, but is important to diagnose because of the possible haemorrhagic complications encountered. We describe the main therapeutic options available today to prevent bleeding during major surgery.

Introduction: Willebrand's syndrome is rarely acquired. We report four cases associated with lymphoproliferative syndromes., Case Reports: We observed four patients with lymphoid hemopathies who developed acquired Willebrand's syndrome. Two patients had Waldenström's disease (kappa), one had a monoclonal gammapathy of undetermined signification (kappa immunoglobulin M) and the fourth had chronic lymphoid leukemia with mast cell infiltration of the skin. Anti-vWFRCo antibodies were evidenced in only 1 case. Chemotherapy, used in 3 cases, improved hemostasis in one patient. Intravenous immunoglobulins (1 patient) and desmopressin (2 patients) were ineffective. The pathogenic mechanisms and possible therapeutic approaches to acquired Willebrand's syndrome are discussed., Discussion: Acquired Willebrand's syndrome rarely occurs in association with lymphoproliferative disorders appears to be uncommon but the frequency is probably underestimated because appropriate tests are not always performed. The diagnostic search is important however since the hemostasis disorders due to acquired Willebrand's syndrome could be corrected if appropriate etiological treatment is given.

The frequency of HLA antigens was determined in 28 unrelated patients with Willebrand's disease and in 326 healthy controls. There was no significant difference between the two groups for any of the HLA antigens tested. Segregation analysis processed among the families of 26 of these patients didn't allow us to find any disorder of the HLA antigens distribution in the patient's group: transmission of the disease and transmission of the HLA haplotypes appear to be independant in 25 of 26 families studied. There is no linkage and no association between the Willebrand's disease genes and the HLA system genes.

A radioimmunological method for the estimation of anti-haemophilic factor A was perfected and studied, making it possible to measure factor VII antigen as distinct from procoagulant factor VIII activity. The method uses a rabbit anti-factor VIII antibody, purified and labelled with I125. The technique of estimation is based upon the differential precipitability of specific factor VIII antigen-antibody complexes, which precipitate with 25 per cent saturated ammonium sulphate and of free antibody which does not precipitate under these conditions. The method is reproducible and sensitive, with the possibility of measuring 0.3 per cent of factor VIII antigen, i.e. 0.003 units/ml. Its specificity is confirmed by the absence of factor VIII antigen in a patient suffering from a severe form of von Willebrand's disease. Using this technique, normal subjects were found to have 96 +/- 31 per cent of factor VIII antigen in comparison with a pool of 25 normal plasmas. Haemophiliacs tested had, as would have been expected, antigen levels close to normal.

Factor VIII-related antigen is measured by ELISA as follows: Factor VIII-R: Ag is first "captured" between rabbit antibodies to human factor VII R : Ag adsorbed in polystyrene tubes, and conjugate (peroxydase-labelled rabbit antibodies). A chromogenic enzyme substrate is then added and absorbence measurement allows subsequent assay. This method is sensitive, reproducible and specific. The comparison between the results obtained by this enzyme immuno-assay and the electro-immunodiffusion assay (EIA) is interesting for the study of quantitative and qualitative variations of F VII R : Ag in von Willebrand's disease. Two observations of von Willerbrand variants are described in detail : VIII R : Ag plasma level of the first one is normal using EIA but decreased using ELISA, its electrophoretic mobility is increased; in the second case we found typical anomalies of von Willebrand except the VIII R : Ag level normal by the two methods.

Immuno-affinity chromatography on immunoglobulins from a rabbit immunised with the plasma of a patient devoid of factor VII R : Ag allows the elimination of certain contaminants from preparations already enriched in factor VIII. The biological activity and criteria of purity of the factor VIII R : Ag preparation obtained are presented.