Type IIB von Willebrand's disease is a distinct form of this disorder, in which there are abnormal factor VIII/von Willebrand factor multimers in plasma (but normal multimers in platelets) and heightened interaction between the von Willebrand factor and platelets in the presence of ristocetin. We have found that infusion of desmopressin acetate (1-desamino-8-D-arginine vasopressin [DDAVP]), an agent used in the treatment of von Willebrand's disease, causes platelet aggregation and thrombocytopenia in patients with Type IIB disease. In vitro, platelets in normal plasma and those obtained from patients with Type IIB disease before DDAVP infusion aggregated upon the addition of platelet-poor plasma from Type IIB patients treated with DDAVP. Platelet aggregation was associated with adsorption of multimers of factor VIII/von Willebrand factor onto the platelets and was inhibited by EDTA. We conclude that in Type IIB von Willebrand's disease, DDAVP releases an abnormal factor with platelet-aggregating properties. DDAVP should not be used to treat patients with Type IIB disease, since the presence of platelet aggregates in the circulation may be harmful.

Factor VIII procoagulant activity (VIII:C) and factor VIII procoagulant antigen (VIII:CAg) were studied in seven patients with haemophilia A after administration of three different factor VIII concentrates or plasma. The in vivo recovery of VIII:CAg was less than that of VIII:C and the disappearance rate of VIII:CAg was much higher either when concentrates or plasma were given. The half-life of VIII:C was thus about 12 h but of VIII:CAg only about 3 h or less. Six patients with von Willebrand's disease were studied after administration of AHF-Kabi. In contrast to haemophilia A the discrepancy between VIII:C and VIII:CAg disappearance rates was not present in von Willebrand's disease, since both VIII:C and VIII:CAg showed a typical progressive increase. We conclude that factor VIII:C given to haemophilia patients does not behave like native VIII:C, not even when fresh plasma is used. Patients with von Willebrand's disease are capable of forming a normal VIII:C when appropriately stimulated.

Antihaemophilic‐factor‐A‐antibodies, which had spontaneously arisen in 2 patients, were used to develop an immunoradiometric method for measurement of antihaemophilic factor A antigen (VIII:CAg). 13 patients with severe haemophilia A had VIII:CAg below the limit of detection (0.01 U/ml). Patients with moderate and mild haemophilia A either had VIII:CAg roughly equal to factor VIII clotting activity (VIII:C) or a not detectable VIII:CAg, suggesting 2 different molecular mechanisms in moderate and mild haemophilia A. VIII:CAg could be detected in serum but in lower amounts than in plasma. In 2 patients with von Willebrand's disease VIII:CAg equalled VIII:C. The post‐transfusional retarded increase of VIII:C in 1 patient with von Willebrand's disease was accompanied by a slight increase in VIII:CAg. Fetal plasma contained measurable amounts of VIII:CAg.

Factor VIII related activities were investigated in 3 low purity concentrates (fraction 1‐0 and freeze‐dried cryoprecipitates), 2 intermediate concentrates, and 8 high purity concentrates. The parameters studied were VIII:C by one‐stage assay and chromogenic assay, VIII clotting antigen (VIII:CAg), VIII related antigen (VIIIR:Ag) by electroimmunoassay, immunoradiometric assay (IRMA), crossed immuno‐electrophoresis (CIE) and SDS agarose gel electrophoresis followed by staining with radioactive antibody, ristocetin cofactor activity (R:RCF) and fibrinogen. The VIII:C values from the chromogenic assay method agreed well with those obtained by the one‐stage assay. The specific activity varied considerably between the different concentrates and even between different batches. DDAVP Octonativ and Factorate had the highest specific activity. With the exception of Factorate, all preparations had higher concentrations of VIII:CAg than of VIII:C — probably indicating inactivation of the biological activity of VIII:C during the manufacturing process. Studies of the Factor VIII/von Willebrand factor showed that all the concentrates contain considerable amounts of VIIIR:Ag as measured by electroimmunoassay. The intermediate and the high purity concentrates had much lower concentration of VIIIR:Ag as determined by IRMA than by electroimmunoassay, and the dose response curves were non‐parallel. On CIE they showed an abnormal migration. Multimeric sizing demonstrated that all the intermediate and high purity concentrates were lacking in the high molecular weight multimers. Fraction 1‐0 and the cryoprecipitates, the only preparations capable of correcting the bleeding defect in patients with von Willebrand's disease, showed about the same concentration of VIIIR:Ag as determined by electroimmunoassay and IRMA, normal migration in CIE, and the same multimeric pattern as normal plasma. The VIIIR:RCF values were much lower than those for VIIIR:Ag, as determined by electroimmunoassay. Thus, considerable differences were found of the in vitro properties of Factor VIII related activities between low, intermediate and high purity Factor VIII concentrates. The action of proteases and the techniques used in purification probably have a crucial effect on the properties.

VIII:C (one-stage) and VIII:CAg (solid phase IRMA using both two homologous nonhaemophilic antibodies and a haemophilic antibody against VIII: C, Holmberg et al 1979, Scand. J. Haemat. 23, 17) were studied in 8 patients with severe, and 2 with mild, haemophilia A after administration of 3 different f VIII concentrates (AHF-Kabi, Hemofil, high purity Factorate) or fresh citrated plasma or heparin plasma. The recovery of VIII: C was about the same for all the preparations (70–100 %), but that of VIII: CAg considerably less (30–50 %). When the concentrates were added in vitro to the haemophilia plasma (the patients all multitransfused) the recovery of VIII:C was about 100 % but that of VIII: CAg only 30–50 %. In normal plasma the recovery of VIII: CAg was 100 %. When the concentrates were added to haemophilia plasma depleted from IgG (protein A Sepharose) the recovery of VIII: CAg was about 100 %. This indicates that most haemophiliacs have antibodies reacting with the f VIII coagulant protein with little or no interference with the coagulant activity. The half-life of VIII:C was about 12 h, but that of VIII:CAg only 3 h or less. We also infused fresh citrated plasma into 2 haemophiliacs, but the results were the same. The response to transfusion observed in haemophilia indicates a change in the native properties of f VIII already on collection of blood. This might be due to the decalcification with citrate. Thus, in preliminary experiments using fresh heparin plasma the curves for the disappearance rate of VIII: C and VIII: CAg were parallel.