| 1. |
- Auerswald, Guenter, et al.
(författare)
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Beyond patient benefit: clinical development in hemophilia
- 2012
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Ingår i: Hematology. - 1607-8454. ; 17:1, s. 1-8
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Forskningsöversikt (refereegranskat)abstract
- Historically in hemophilia, outcome measures have not been collected systematically. Hence, there are insufficient clearly defined, evidence-based measures that can be applied consistently across hemophilia trials. This review focuses on some key challenges to evaluating patient outcomes and performing trials identified by experts at the Fourth and Fifth Zurich Haemophilia Forums. As procedures appear inconsistent across Europe, guidelines require modification to be more appropriate and/or realistically achievable. The outcome measures utilized, and the timing of their collection, should also be standardized, and more objective measures used where feasible. Implementation of outcome measures could be refined through greater understanding of patient heterogeneity, and tailored to differentiate between hemophilia- and aging-related disease effects. Furthermore, robust outcome measures that can also inform health-economic decisions are increasingly needed. Lastly, as patient recruitment poses a challenge, the panel proposed a call for action to motivate physicians and patients to participate in clinical trials.
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| 2. |
- Benson, Gary, et al.
(författare)
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Immune tolerance induction in patients with severe hemophilia with inhibitors: expert panel views and recommendations for clinical practice.
- 2012
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Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 88:5, s. 371-379
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Tidskriftsartikel (refereegranskat)abstract
- For hemophilia patients with inhibitors, immune tolerance induction (ITI) may help to restore clinical response to Factor (F) VIII or FIX concentrates. Several ITI regimens and protocols exist; however, despite 30 yr of progressive investigation, the ITI evidence base relies mainly on observational data. Expert opinion, experience, and interpretation of the available evidence are therefore valuable to support clinical decision-making. At the Sixth Zürich Haemophilia Forum an expert panel considered recent data and consensus to distill key practice points relating to ITI. The panel supported current recommendations that, where feasible, ITI should be offered early to children and adults (ideally ≤5 yr of inhibitor detection) when inhibitor titers are <10 Bethesda Units, and should be stopped when successful tolerance is achieved. For hemophilia A inhibitor patients, ITI can be founded on recombinant FVIII at high doses. The panel considered that patients with a high bleeding frequency should be offered additional prophylaxis with a bypassing agent. For hemophilia B patients, there may be a benefit to genetic testing to indicate the risk for inhibitors. ITI is often less effective and associated with a greater risk of side effects in these patients. For high-titer inhibitor (≥5 Bethesda Units) hemophilia B patients, the panel advised that bypassing agents could be offered on demand in addition to ITI. Within future ITI regimens there may be a role for additional immunosuppressant therapies. Participants agreed that research is needed to find alternatives to ITI therapy that offer durable and sustained effects and reduced rates of complications. © 2012 John Wiley & Sons A/S.
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| 3. |
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| 4. |
- Ljungkvist, Marcus, et al.
(författare)
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Correlation to FVIII : C in two thrombin generation tests: TGA-CAT and INNOVANCE ETP
- 2017
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Ingår i: Mediterranean Journal of Hematology and Infectious Diseases. - : Institute of Hematology, Catholic University. - 2035-3006. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Several thrombin-generation tests are available, but few have been directly compared. Our primary aim was to investigate the correlation of two thrombin generation tests, thrombin generation assay-calibrated automated thrombogram (TGA-CAT) and INNOVANCE ETP, to factor VIII levels (FVIII:C) in a group of patients with hemophilia A. The secondary aim was to investigate inter-laboratory variation for the TGA-CAT method. Methods: Blood samples were taken from 45 patients with mild, moderate and severe hemophilia A. The TGA-CAT method was performed at both centers while the INNOVANCE ETP was only performed at the Stockholm center. Correlation between parameters was evaluated using Spearman's rank correlation test. For determination of the TGA-CAT inter-laboratory variability, Bland-Altman plots were used. Results: The correlation for the INNOVANCE ETP and TGA-CAT methods with FVIII:C in persons with hemophilia (PWH) was r=0.701 and r=0.734 respectively. The correlation between the two methods was r=0.546. When dividing the study material into disease severity groups (mild, moderate and severe) based on FVIII levels, both methods fail to discriminate between them. The variability of the TGA-CAT results performed at the two centers was reduced after normalization; before normalization, 29% of values showed less than ±10% difference while after normalization the number increased to 41%. Conclusions: Both methods correlate in an equal manner to FVIII:C in PWH but show a poor correlation with each other. The level of agreement for the TGA-CAT method was poor though slightly improved after normalization of data. Further improvement of standardization of these methods is warranted.
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| 5. |
- Suvajdzić-Vuković, Nada, et al.
(författare)
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Rezultati lecenja trombozne trombocitopenijske purpure na 36 bolesnika
- 2004
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Ingår i: Vojnosanitetski Pregled. - 0042-8450. ; 61:6, s. 7-621
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-six patients (pts.) with thrombotic thrombocytopenic purpura (TTP) were treated between May 1990 and May 2003. There were 31 women and 5 men; the average age was 37 years. Twenty-five cases were idiopathic and 11 secondary (3 infection--related, 5 occurred during pregnancy and 3 were drug--associated). The mean lag period between the first symptoms and the diagnosis was 8.5 days (in 14 pts. < or = 5; in 22 > 5). On diagnosis neurological symptoms were present in 31, bleeding in 33, fever in 21 and renal impairment in 27 patients. The mean hemoglobin was 67.5 g/L, the mean platelet count was 10 x 10(9)/L, and the mean reticulocytosis was 17%. The mean serum LDH was 1457 IU. Treatment included plasma exchange (PE) in 24 pts. and only plasma infusions in 12 pts. There were 24 complete responders (20 on PE) and 12 deaths (4 on PE); PE significantly improved survival (p < 0.01). There were 5 treatment-related complications due to the infection and bleeding, 17 exacerbations and 4 relapses. The mean time delay before the onset of symptoms and the treatment initiation lasted for 9 days suggesting the poor disease recognition; the mean time delay from diagnosis to PE institution was 6 days, indicating postponed PE. The mean treatment duration in all patients was 18 days; the mean number of PE cycles needed for the platelet count stabilization was 9. Good prognostic indicators of survival were: the longer prodromal period (> 5 days), the secondary form of TTP and the absence of coma at presentation. The use of PE significantly improved survival. TTP is a severe disorder requiring early recognition and diagnosis in general medical care facilities, which should lead to the timely treatment with PE.
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| 6. |
- Sørensen, Benny, et al.
(författare)
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Rationale for individualizing haemophilia care.
- 2015
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 26:8, s. 849-857
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Forskningsöversikt (refereegranskat)abstract
- Owing to the heterogeneity in the clinical phenotype of haemophilia A and B, it is now recognized that disease severity (based on factor VIII/IX activity) may no longer be the most appropriate guide for treatment and that a 'one-size-fits-all' approach is unlikely to achieve optimal therapy. Based on the present literature and consensus views of a group of experts in the field, this article highlights key gaps in the understanding of the diverse relationships between bleeding phenotype and factors such as joint health, genetic susceptibility, laboratory parameters, quality of life and management of pain. Early prophylaxis is a potential 'gold standard' therapy and issues surrounding inhibitor development, variations in its clinical use and long-term outcomes are discussed. Comprehensive treatment should be individualized for all patients (including those with mild or moderate haemophilia and carriers). Wherever possible all patients should be given prophylaxis. However, adult patients with a milder haemophilia phenotype may be candidates for ceasing prophylaxis and switching to on-demand treatment. Regardless, all treatment (on-demand and prophylaxis) should be tailored towards both the patient's personal needs and their clinical profile. In addition, as the associations between risk factors (psychosocial, condition-related and treatment-related) and clinical features are unique to each patient, an individualized approach is required to enable patients to alter their behaviour in response to them. The practical methodologies needed to reach this goal of individualized haemophilia care, and the health economic implications of this strategy, are ongoing topics for discussion.
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