The genetic defect of type I von Willebrand disease "Vicenza" is linked to the von Willebrand factor gene.

Type I von Willebrand disease (vWD) Vicenza is a rare variant with autosomal dominant transmission, characterized by the presence of supranormal von Willebrand factor (vWF) multimers in plasma, similar to those normally found in endothelial cells and megakaryocytes. The patients have very low levels of plasma vWF contrasting with a mild bleeding tendency. The pathophysiology of this subtype is still unknown. The presence of supranormal multimers in the patients' plasma could be due to a mutation in the vWF molecule which affects post-translational processing, or to a defect in the cells' processing machinery, independent of the vWF molecule. In order to determine if type I vWD Vicenza is linked to the vWF gene, we studied six polymorphic systems identified within the vWF gene in two apparently unrelated families with type I vWD Vicenza. The results of this study indicate a linkage between vWF gene and the type I vWD Vicenza trait. This strongly suggests that type I vWD Vicenza is due to a mutation in one of the vWF alleles, which results in an abnormal vWF molecule that is processed to a lesser extent than normal vWF.

Platelet von Willebrand factor assay: results using two methods for platelet lysis.

Two different methods (using Triton X-100 and glycerol) for lysing platelets to measure platelet vWF concentrations were compared directly. The platelet concentration of von Willebrand factor antigen (vWF:Ag) was similar for both methods, whereas ristocetin cofactor activity (Ricof) was higher with Triton than with glycerol. After storing platelet lysates for two months at -80 degrees C vWF:Ag and Ricof concentrations decreased with both methods of lysis. Larger than normal (supranormal) vWF multimeric forms could be visualized in platelet lysates obtained using both methods, with no change of the multimeric pattern during storage. Triton can be recommended as the agent of choice to lyse platelets for measurement of their vWF concentration, but the samples must be assayed within two weeks to avoid decay of Ricof activity.

Successful pregnancy in a woman with congenital factor XIII deficiency treated with substitutive therapy. Report of a second case.

A syndrome of marked fetal wastage is associated with congenital factor XIII deficiency in adult women. A previously unreported case of a woman with factor XIII deficiency is described, in which substitutive treatment with normal plasma or placental factor XIII concentrate permitted two normal pregnancies. Factor XIII activity was maintained above 1-2% with intermittent infusion of 300 ml to 450 ml of plasma every 14 days or of 500 units of concentrate every 21 days. This case confirms the only other case so far reported in which factor XIII substitutive therapy was able to permit a normal pregnancy in a woman with factor XIII deficiency and seems to suggest factor XIII to be involved in the process of annidation.

Fibrinogen Vicenza and Genova II: two new cases of congenital dysfibrinogenemia with isolated defect of fibrin monomer polymerization and inhibitory activity on normal coagulation.

Two new cases of congenital dysfibrinogenemia are presented in which defective fibrin monomer polymerization and inhibitory activity on normal coagulation were observed. They have been tentatively called fibrinogen Vicenza and Genova II. The first was discovered in a family with mild bleeding diathesis, the second in an asymptomatic family. In almost all reported cases of fibrinogens with defective fibrin monomer polymerization, additional functional or structural defects have been detected. In our cases, on the contrary, detailed investigations failed to show any other abnormality. Fibrinogen Genova II is apparently identical to fibrinogen Baltimore IV, whereas fibrinogen Vicenza is similar to fibrinogen Troyes and Genova I, but also exerts an evident inhibitory activity on normal coagulation and differs from fibrinogen Genova II and Baltimore IV showing a different kinetic pattern of fibrin monomer polymerization.

One year follow-up study of T-cell subsets and incidence of seropositivity for HTLV-I and HTLV-III antibodies in patients treated "on demand" or sporadically with clotting concentrates.

A 1-year follow-up study of the T-cell subset abnormalities was carried out in 16 severe haemophilia A patients, treated "on demand" with an average amount of 500 U/kg/yr of factor VIII concentrate (group A) and in 15 mild haemophiliacs or von Willebrand patients treated only sporadically with less than 3000 U of factor VIII and no longer exposed to any other blood component in the 2 years preceding the beginning of the study (group B). In group A, 50% and 70% of patients showed a reduced or inverted T 4/T 8 ratio, respectively, at the beginning and at the end of follow-up. These values were of 30% and 20% in patients of group B, suggesting a long-lasting effect of concentrate therapy on T-cell subsets. The low T 4/T 8 ratio was mainly due to an increase of suppressor cells. None of the patients was found positive for anti HTLV-I, whereas 3 patients, all belonging to the group A, showed antibodies against HTLV-III. Thus, in these patients, HTLV-III seems not to be the only cause of low T 4/T 8 ratio.