The use of intermediate and high purity factor VIII products in the treatment of von Willebrand disease.

Since 1985, viral-attenuated blood products have been available for the treatment of patients with hemophilia. Unfortunately, similar viral-attenuated blood products, enriched for von Willebrand factor (vWF), have not been readily available for the treatment of patients with von Willebrand disease (vWD). In the current study, we examined the clinical efficacy and in vivo properties of two viral-attenuated factor VIII products, Koate-HS and Koate-HP, in the treatment of patients with vWD. Twenty-one (21) infusions were evaluated in 17 different vWD patients (4 with type IA; 8 with Type IIA; 1 with Type IID; 4 with type III). Seven (7) patients received Koate-HS and 12 patients received Koate-HP (2 patients received both products; 1 patient was studied three times). Von Willebrand factor antigen, ristocetin cofactor, bleeding time, and the multimeric composition of vWF were determined pre- and post-infusion. Complete or partial correction of prolonged bleeding times was observed in 2 of the 6 patients tested following treatment with Koate-HS and in 7 out of 11 patients tested following treatment with Koate-HP. Surgery was performed on five of these patients, two of whom were treated with Koate-HS and three of whom were treated with Koate-HP. In the surgical patients, clinical hemostasis was achieved regardless of whether the bleeding time was corrected. We conclude that both Koate-HS and Koate-HP can be utilized successfully in the treatment of patients with vWD in spite of the lack of high molecular weight multimers of vWF in these products.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of cytoskeleton in isotonic cell volume control of rabbit proximal tubules.

Stability of mammalian cell volume depends primarily on the sodium pump. When active cation transport of rabbit renal proximal tubules is blocked by ouabain, cells swell, but their size is limited by residual volume control mechanisms. This "ouabain-resistant" volume control is not an active process, as it operates in the presence of cyanide and dinitrophenol and in the absence of exogenous energy. Nevertheless, it remains incompletely explained by known transmembrane oncotic and hydrostatic forces. We tested the hypothesis that the cytoskeleton contributes to isotonic cell volume control. Isolated, collapsed rabbit proximal convoluted tubules (PCT) were crimped at both ends with micropipettes and had their volume assessed optically. PCT in ouabain (1 mM) swelled to 1.40 above control with protein, 1.62 without protein, and 1.89 with the cytoskeleton inhibitors vincristine (5 microM) and cytochalasin B (50 microM) and without protein. Tubulozole-C and cytochalasin D gave similar results. A hydrostatic pressure of 50 cmH2O increased tubule volume to 1.93 before the tubule basement membrane (TBM) prevented further volume increase. We conclude that volume of renal tubule cells in ouabain is limited partly by external protein, but primarily by the cytoskeleton. The TBM prevents massive swelling and tubule disaggregation.