Combined administration of FVIII and rFVIIa improves haemostasis in haemophilia A patients with high-responding inhibitors--a thrombin generation-guided pilot study.

Treatment of haemophilia A patients with inhibitors is challenging, and may require individually tailored regimens. Whereas low titre inhibitor patients may respond to high doses of factor VIII (FVIII), high-responding inhibitor patients render replacement therapy ineffective and often require application of bypassing agents. Thrombin generation (TG) assays may be used to monitor haemostasis and/or predict patients' response to bypass agents. In this study we defined by TG, the potential contribution of FVIII to recombinant activated factor VII (rFVIIa)-induced haemostasis in inhibitor plasma. Based upon results, prospectively designed individual regimens of coadministration of rFVIIa and FVIII were applied. Plasma samples from 14 haemophilia patients with inhibitors (including high titre inhibitors) were tested. The response to increasing concentrations of FVIII, rFVIIa or both was assayed by TG. Eight patients, chosen following consent and at physician's discretion, comprised the combined FVIII-rFVIIa therapy clinical study cohort. Combined spiking with FVIII/rFVIIa improved TG induced by rFVIIa alone in all inhibitor plasmas. Combined rFVIIa and FVIII therapy was applied during bleeding or immune tolerance to eight patients, for a total of 393 episodes. Following a single combined dose, 90% haemostasis was documented and neither thrombosis nor any complications evolved. During study period decline of inhibitor levels and bleeding frequency were noted. Pre-analytical studies enabled us to prospectively tailor individual therapy regimens. We confirmed for the first time that the in vitro advantage of combining FVIII and rFVIIa, indeed accounts for improved haemostasis and may safely be applied to inhibitor patients.

An easy sonochemical route for the encapsulation of tetracycline in bovine serum albumin microspheres.

A one-step sonochemical process starting with the native BSA and tetracycline was employed to encapsulate the antibiotic drug in microspheres of BSA. The tetracycline loading studies showed that the maximum tetracycline loading capacity was found to be 65%. The antimicrobial activity of the tetracycline loaded in BSA microspheres was demonstrated on two bacterial strains that are sensitive to tetracycline.

The preparation of magnetic proteinaceous microspheres using the sonochemical method.

Using high-intensity ultrasound, we have developed a method for the synthesis of magnetic microspheres. The microspheres are composed of iron oxide-filled and coated globular bovine serum albumin (BSA). The magnetic microspheres are prepared from BSA and iron pentacarbonyl, or from BSA and iron acetate. Transmission electron microscopy and scanning electron microscopy show spherical particles. The particle size distributions are gaussian, with a mean diameter of a few micrometers. Using chemical analysis, it was found that the total percentage of iron oxide in the microspheres is between 39% and 42%. Mössbauer measurements were also performed.