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- Castaman, G., et al.
(författare)
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Validation of a rapid test (VWF-LIA) for the quantitative determination of von Willebrand factor antigen in type 1 von Willebrand disease diagnosis within the European multicenter study MCMDM-1VWD
- 2010
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Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 126:3, s. 227-231
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accurate measurement of von Willebrand factor (VWF) is a critical requirement for the diagnosis of von Willebrand disease (VWD). Aim of the study: To evaluate the diagnostic efficiency of a rapid quantitative test for the measurement of VWF antigen (VWF:Ag) in type 1 VWD. Patients and methods: VWF: Ag was measured with an ELISA in a robotic instrument, as a reference method, and with a fully automated latex-immunoassay (LIA) on an ACL 9000 analyser in 1,716 subjects enrolled within the Molecular and Clinical Markers for Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD) Study. Among these subjects, 1,049 were healthy controls, 281 healthy family members and 386 affected members from 127 European families with type 1 VWD. Results: The assay linearity range was 10-125 IU/dL for LIA (R-2 = 0.99) and 5-133 IU/dL for ELISA (R-2 = 0.99). The inter-assay CV for low VWF levels (similar to 30 IU/dL) was 2% for the LIA test and 8.7 % for ELISA. The sensitivity for detection of type 1 VWD affected members was 86% and the specificity 91% for LIA, 87% and 90% for ELISA. A receiver-operator (ROC) analysis disclosed only a marginal difference between the two tests, LIA having a slightly greater area under the curve (0.94 vs. 0.93, p = 0.03). Conclusion: VWF: Ag LIA compared well to standard ELISA in this large population of patients and controls, showing better CV. However the lower detection limit for the VWF: Ag LIA compared to the VWF: Ag ELISA means that the LIA assay is less good at discriminating between type 3 VWD and moderate type 1 VWD. (C) 2010 Elsevier Ltd. All rights reserved.
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- Tiede, A, et al.
(författare)
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Safety and pharmacokinetics of subcutaneously administered recombinant activated factor VII (rFVIIa).
- 2011
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 9, s. 1191-1199
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recombinant factor VIIa (rFVIIa) is used to treat bleeds in hemophilia patients with inhibitors. A subcutaneous formulation could potentially improve its half-life and make it suitable for prophylactic treatment. Objectives: A study was conducted to determine the safety of subcutaneously administered rFVIIa in patients with hemophilia and the pharmacokinetic profile (including bioavailability). Patients/Methods: This was a multi-center, open-label, cross-over comparison of single doses of intravenous rFVIIa 90 μg/kg and a new formulation of rFVIIa for subcutaneous injection at dose levels of 45, 90, 180, 270 and 360 μg/kg. Sixty subjects (12 per dose cohort) with hemophilia A or B were enrolled. Results: Subcutaneously administered rFVIIa showed lower mean peak plasma concentrations and prolonged FVII activity (C(max) :0.44-5.16 IU/mL [across doses], t(1/2) :12.4 hours, t(max) :5.6 hours) compared with intravenously administered rFVIIa (C(max) :51.7 IU/mL, t(1/2) :2.7 hours, t(max) :<10 minutes). The absolute bioavailability of subcutaneous rFVIIa ranged from 21.1%-30.1% across dose levels. Dose proportionality was observed within a 2-fold dose increase but not across the full dose range. No thromboembolic events, drug-related serious adverse events, severe injection-site reactions or neutralizing antibodies were reported (primary endpoint). Mild and moderate injection-site reactions were more frequent with subcutaneous than with intravenous injections. Conclusion: This phase I clinical trial did not identify safety concerns of prolonged exposure to rFVIIa administered subcutaneously in single doses to hemophilia patients.
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