| 1. |
- Astermark, Jan, et al.
(författare)
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Antibodies to factor VIIa in patients with haemophilia and high-responding inhibitors.
- 2002
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 119:2, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- The haemostatic effect of by-passing agents such as activated prothrombin complex concentrates (aPCC) and recombinant factor VIIa is inadequate in some patients with severe haemophilia and high-responding inhibitors. Theoretically, this could be due to antibody reactivity to procoagulant proteins other than the deficient factor. To evaluate this hypothesis, immunoglobulin (Ig) fractions from six multi-transfused patients (three haemophilia A and three haemophilia B) were purified on protein A sepharose and then subjected to immunoaffinity chromatography on factor IX sepharose and factor VIIa sepharose. All three Ig fractions from the haemophilia B patients, but not commercially available Ig, contained antibodies that bound to both gels. None of the haemophilia A patients had antibodies to factor IX but all three had antibodies towards factor VIIa. The immunoaffinity purified antifactor IX and VIIa antibodies from the haemophilia B patients inhibited thrombin formation in vitro using Feiba(R) as active enzyme, but had no significant effect in the presence of NovoSeven(R). In contrast, no inhibitory effect was observed with the antifactor VIIa antibodies from the haemophilia A patients. Cross-reactivity to factor IX was seen for the antifactor VIIa antibodies from the patients with haemophilia B. Our findings show that antibody reactivity to other procoagulant factors such as factor VIIa exists in patients with high-responding inhibitors and that these antibodies may have an inhibitory potential that correlates to the amount of active enzyme present. The characterization of the antibody profile may facilitate an optimal treatment with by-passing agents in severe bleeding events.
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| 2. |
- Astermark, Jan, et al.
(författare)
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No effect of a new second-generation B-domain-deleted recombinant product on lymphocyte transformation in vitro: a study of plasma-derived and recombinant products
- 1997
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 99:2, s. 289-294
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Tidskriftsartikel (refereegranskat)abstract
- Immunomodulatory effects of various factor VIII and factor IX clotting factor concentrates (CFCs) and of albumin were evaluated by a sensitive assay measuring the incorporation of 3H-thymidine in phytohaemagglutinin-stimulated lymphocytes in the presence of monodansylthiacadaverine. In contrast to previous findings by others, we found lymphocyte transformation to be inhibited by all plasma-derived factor VIII concentrates at concentrations of 0.02, 0.2 and 2.0 IU/ml, including those purified by monoclonal antibodies (P < 0.05). Kryobulin TIM3 had the most pronounced effect. In addition, three plasma-derived human albumin preparations exerted a similar inhibitory effect as the factor VIII concentrates, whereas the corresponding plasma-derived factor IX concentrates only manifested minor immunomodulatory effects. Of the recombinant preparations, only Recombinate exerted an inhibitory effect at 0.02 and 0.2 IU/ml, whereas both Kogenate and Recombinate decreased 3H-thymidine incorporation at 2.0 IU/ml (P = 0.01). No immunomodulatory effect at all was observed with r-VIII SQ, a new B-domain-deleted recombinant factor VIII preparation free from added albumin. The significance of this finding regarding immunological side-effects including inhibitor development remains to be evaluated, but this second-generation recombinant product opens up new and interesting perspectives yet to be explored.
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| 3. |
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| 4. |
- Ekman, Stefan, 1972-, et al.
(författare)
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Literatura Niewidocznego : Wizje i rewizje urban fantasy
- 2018
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Ingår i: Creatio Fantastica. - : Facta Ficta Research Centre. - 2300-2514. ; 58:1, s. 177-188
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A discussion Literature of the Unseen—Visions and (Re)visions of Urban Fantasy collects theoretical reflections upon the subgenres of urban fantasy and paranormal romance, along with a brief commentary on the body of text representative for both conventions. Participants include „Creatio Fantastica” editors—Sylwia Borowska-Szerszun, Krzysztof M. Maj, and Barbara Szymczak-Maciejczyk—as well as renowned experts in the field of fantasy studies: Stefan Ekman, author of the first monograph of fantasy map-making, Here Be Dragons. Exploring Fantasy Maps & Settings (2013), and Audrey Taylor, author of Patricia A. McKillip and the Art of Fantasy World-building (2017).
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| 5. |
- Freiburghaus, Christian, et al.
(författare)
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Immunoadsorption for removal of inhibitors: update on treatments in Malmo-Lund between 1980 and 1995
- 1998
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 4:1, s. 16-20
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of severe bleeding and the performance of surgery in haemophilia patients with inhibitors creates severe problems. It is generally agreed that treatment is most effective if circulating levels of factor VIII/IX can be achieved long enough for control of haemostasis. Immunoadsorption with protein A for the removal of inhibitor has improved treatment for patients with initial inhibitor titres too high to neutralize by infusion alone. This is a summary of our experience in Malmo regarding immunoadsorption and haemostasis. A total of 19 applications with immunoadsorption in 10 patients were performed. On all occasions it was possible to eliminate totally the inhibitor or reduce it to low levels that could easily be neutralized with factor concentrate. Haemostatic levels of coagulation factors could be maintained for 5-9 days in all but one patient. This period was sufficient to stop ongoing haemorrhage or prevent excessive bleeding at surgical interventions.
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| 6. |
- Freiburghaus, Christian, et al.
(författare)
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Tolerance induction using the Malmo treatment model 1982-1995
- 1999
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 5:1, s. 32-39
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Tidskriftsartikel (refereegranskat)abstract
- The ultimate goal in the treatment of haemophilia patients with inhibitors is to eradicate permanently the inhibitor and induce tolerance. Here we summarize our experience at the Malmo centre regarding tolerance induction according to the Malmo Treatment Model. The protocol includes immunoadsorption if needed, neutralization of inhibitor and replacement with factor concentrates, cyclophosphamide intravenously for 2 days (12-15 mg kg-1 bw) and then orally (2-3 mg kg-1 bw) for an additional 8-10 days and intravenous gammaglobulin daily at dosages of 0.4 g kg-1 bw for 5 days. This protocol has been applied in 23 haemophilia patients with inhibitors, 16 haemophilia A patients and seven haemophilia B patients. Altogether 36 attempts have been made to induce tolerance. Ten of the 16 haemophilia A (62.5%) and 6/7 patients with haemophilia B (86%) became tolerant after the treatment. The chances of success or failure are roughly equal, if the series is considered in a historical perspective. The data showed that the chances of success in tolerance induction with the Malmo protocol were best in those patients with low inhibitor titres, with relatively low historical inhibitory peak and with a long interval since the previous replacement therapy. This was especially true where no inflammatory state was present at the start or during tolerance induction. The advantage with this method compared to the high-dose regimen is that in the successful cases tolerance can be achieved within 3-4 weeks.
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| 7. |
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| 8. |
- Salvagno, G. L., et al.
(författare)
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Impact of different inhibitor reactivities with commercial factor VIII concentrates on thrombin generation
- 2007
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 13:1, s. 51-56
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Tidskriftsartikel (refereegranskat)abstract
- In order to describe the haemostatic role of a variation in inhibitor reactivity with different factor VIII (FVIII) concentrates, we have compared inhibitor titres against a panel of FVIII concentrates and correlated titre with the capacity to inhibit thrombin generation. Three plasma-derived concentrates were tested in vitro in mixing experiments with inhibitor plasmas from 11 patients with severe haemophilia A: Fanhdi, which contains von Willebrand factor (VWF) with a final ratio of approximately 1:1 (VWF IU per IU FVIII:Q; Haemate-P with a ratio of 2.5:1 and Hemofil-M containing only trace amounts of VWF. In addition, the recombinant FVIII concentrate Kogenate Bayer containing no VWF was included. Inhibitor titres and the capacity to generate thrombin were measured. A statistically significant difference in measured titres was found with the highest titres recorded against Hemofil-M. The inhibitor titres needed to inhibit 50% maximum thrombin generation were the lowest for Kogenate Bayer and the highest and similar for Fanhdi and Haemate-P with intermediate titres needed for inhibition of Hemofil-M. In this study, the thrombin generation assay provides additional indications for the role of VWF in the treatment of patients with inhibitors. The VWF-containing concentrates Fanhdi and Haemate-P, added to FVIII-deficient plasma with the presence of inhibitor, generate more thrombin than do the purified concentrates Hemofil-M and Kogenate Bayer.
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| 9. |
- Salvagno, G. L., et al.
(författare)
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Thrombin generation assay: a useful routine check-up tool in the management of patients with haemophilia?
- 2009
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 15:1, s. 290-296
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Tidskriftsartikel (refereegranskat)abstract
- Severity assessment of patients with haemophilia A (HA) is traditionally based on FVIII activity (FVIII:C). Clinical phenotype of HA patients often differs between individuals with the same FVIII:C determined with clotting and chromogenic assays. The aim of this study was to assess the influence of the FVIII:C on thrombin generation (TG) assay parameters both in vitro and ex-vivo postinfusion plasma. For in-vitro approach, influence of FVIII:C was evaluated on TG parameters in several dilutions of a normal plasma pool with commercial FVIII-depleted-plasma (FVIIIDP) and in others experiments, adding increasing amounts of different commercial FVIII concentrates (Fanhdi, Haemate-P, Hemofil-M and Kogenate Bayer) to FVIIIDP. In a series of 50 postinfusion samples, from HA patients of different severity, we assayed TG and FVIII:C (chromogenic and clotting). In vitro experiments, the 50% of maximum TG peak (TGMP) was achieved using only 5% FVIII:C and the TGMP was obtained with 40% of normal VIII:C. Impaired response compared with normal plasma was found in FVIIIDP using addition of increasing amounts of different commercial FVIII concentrates. An overall good correlation between the two FVIII assays was observed (y = 0.9115x - 0.273, r = 0.975, P < 0.001); TGMP and the Lag-Phase-Time (LPT) provided some discrepant results when compared with the total range of FVIII:C measurements. In contrast, correlations for TGMP, LPT and endogenous thrombin potential were improved in samples restricted to FVIII:C < 5%. We conclude that TG parameters tentatively could be a tool to tailor the global haemostatic capacity in haemophilic patients.
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