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- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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- Berntorp, E., et al.
(author)
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European retrospective study of real-life haemophilia treatment
- 2017
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In: Haemophilia. - : Wiley. - 1351-8216. ; 23:1, s. 105-114
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Journal article (peer-reviewed)abstract
- Introduction: Haemophilia treatment varies significantly between individuals, countries and regions and details of bleed rates, factor consumption and injection frequency are often not available. Aim: To provide an overview of the FVIII/FIX treatment practice and outcome for patients with haemophilia A (HA) or haemophilia B (HB) across Europe. Methods: Non-interventional, 12-month retrospective study where anonymized data were retrieved from haemophilia centres/registers in Belgium, France, Germany, Italy, Spain, Sweden and the United Kingdom. Male patients (all ages) receiving coagulation factor treatment 24 months prior to the study, with basal FVIII/FIX levels ≤5 IU dL-1, without inhibitors, were included. Data were summarized descriptively. Results: In total, 1346 patients with HA and 312 with HB were included in the analysis; 75% and 57% had severe disease (FVIII/FIX < 1 IU dL-1) respectively. Prophylaxis was most common for severe haemophilia, especially for children, whereas on-demand treatment was more common for moderate haemophilia in most countries. The mean (SD) prescribed prophylactic treatment ranged from 67.9 (30.4) to 108.4 (78.1) (HA) and 32.3 (10.2) to 97.7 (32.1) (HB) IU kg-1 per week, across countries. Most patients on prophylaxis were treated ≥3 times/week (HA) or two times/week (HB). The median annual bleeding rate (ABR) for patients on prophylaxis ranged from 1.0 to 4.0 for severe HA, and from 1.0 to 6.0 for severe HB, while those with moderate haemophilia generally had slightly higher ABRs. Median ABRs for on-demand-treated severe HA ranged from 4.5 to 18.0, and for HB, 1.5 to 14.0. Conclusion: Treatment practice varied greatly between centres and countries and patients treated on-demand and prophylactically both experienced bleeds, emphasizing the need for further optimization of care.
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- Castaman, G., et al.
(author)
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Hemorrhagic symptoms and bleeding risk in obligatory carriers of type 3 von Willebrand disease: an international, multicenter study
- 2006
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In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 4:10, s. 2164-2169
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Journal article (peer-reviewed)abstract
- Objectives: We undertook an international, multicenter study to describe the clinical picture and to estimate the bleeding risk in a group of obligatory carriers of type 3 von Willebrand disease (VWD). Patients and methods: Obligatory carriers (OC) of type 3 VWD were identified by the presence of offspring with type 3 VWD or by being an offspring of a type 3 patient. Normal controls were age- and sex-matched with the obligatory carriers. A physician-administered standardized questionnaire was used to evaluate hemorrhagic symptoms at presentation. A score system ranging from 0 (no symptom) to 3 (hospitalization, replacement therapy, blood transfusion) was used to quantitate bleeding manifestations. Odds ratios were computed for each symptom. Results: Ten centers participated to the study, enrolling a total of 35 type 3 VWD families, with 70 OC. A total of 215 normal controls and 42 OC for type 1 VWD were also included. About 40% of type 3 OC had at least one bleeding symptom compared to 23% of normal controls and 81.8% of type 1 OC (P < 0.0001 by chi-squared test), showing that type 3 OC clearly represent a distinct population from type 1 OC. The clinical situations associated with an increase of bleeding risk in type 3 OC were epistaxis [odds ratio 3.6; 90% confidence intervals (CI) 1.84-21.5], cutaneous bleeding (odds ratio 5.5; 90% CI 2.5-14.1) and postsurgical bleeding (odds ratio 16.3; 90% CI 4.5-59). The severity of bleeding score correlated with the degree of factor (F) VIII reduction in plasma. Conclusions: OC for type 3 VWD represent a distinctive population from type 1 OC. These patients, however, present with more frequent bleeding symptoms in comparison to normal controls, especially in case of significantly low FVIII. Desmopressin and/or tranexamic acid might be useful to prevent or treat bleeding in these cases.
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- Turecek, PL, et al.
(author)
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Factor VIII inhibitor-bypassing agents act by inducing thrombin generation and can be monitored by a thrombin generation assay
- 2003
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In: Pathophysiology of Haemostasis and Thrombosis. - : S. Karger AG. - 1424-8832 .- 1424-8840. ; 33:1, s. 16-22
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Journal article (peer-reviewed)abstract
- Factor VIII (FVIII)-bypassing agents have complex modes of action but all control bleeding in inhibitor patients by triggering the generation of thrombin. No routine test is available for monitoring this therapy in patients with inhibitors against FVIII. We present an assay that records FEIBA- or FVIIa- mediated changes in thrombin generation (TG) in FVIII inhibitor plasma samples. In plasma samples spiked with FEIBA TG was normalized above 0.4 U/ml, while for recombinant FVIIa ( rFVIIa) more than 12.5 mug/ml were required to induce TG in the absence of tissue factor (TF). Addition of TF increased the TG potential of rFVIIa in vitro. This assay seems suitable for monitoring the pharmacokinetics of inhibitor bypassing agents during treatment and possibly for predicting responses to treatment. Copyright (C) 2003 S. Karger AG, Basel.
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- Varadi, K, et al.
(author)
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Monitoring the bioavailability of FEIBA with a thrombin generation assay
- 2003
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In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 1:11, s. 2374-2380
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Journal article (peer-reviewed)abstract
- Background: Hemophilia A patients with inhibitors are generally treated with preparations containing activated coagulation factors to achieve hemostasis by bypassing factor (F)VIII. Objectives: We developed an assay for monitoring the kinetic of thrombin generation in human FVIII inhibitor plasma reconstituted in vitro with activated prothrombin complex concentrate, FEIBA, and in plasma samples from hemophilia A patients taken after FEIBA treatment. Patients and methods: For pharmacokinetic studies three patients with severe hemophilia A and with a high-titer inhibitor received a single dose of FEIBA. Repeated FEIBA treatment was monitored in one patient with acquired hemophilia A. Coagulation was triggered in citrated plasma by adding a low concentration of tissue factor/phospholipid complex and CaCl2 in the presence of a fluorogenic thrombin substrate. The intensity of the fluorescence signal (FU) was continuously monitored, and the rate of increase in the fluorescence signal for every time point, which reflects the actual thrombin concentrations, was calculated. Results: The maximum rate of substrate conversion, which indicates the highest thrombin concentration, was approximately 1900 FU min(-1) in a normal plasma pool. Practically no thrombin generation was observed in the FVIII inhibitor plasma, but when it was spiked with FEIBA, the rate and the peak of thrombin generation increased dose-dependently to close to normal. Plasma samples from FVIII inhibitor patients treated with a single dose of FEIBA had an improved thrombin maximum within an hour after treatment, which gradually returned to baseline values with a half-life of 4-7 h. Changes in the characteristic parameters of thrombin generation coincided with the repeated administration of FEIBA in a patient with acquired hemophilia A. Conclusions: This assay enables the pharmacodynamic and pharmacokinetic properties of bypassing therapies to be monitored, thus helping to optimize treatment.
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