| 1. |
- Abshire, T. C., et al.
(författare)
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Prophylaxis in severe forms of von Willebrand's disease: results from the von Willebrand Disease Prophylaxis Network (VWD PN)
- 2013
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Ingår i: Haemophilia. - Wiley-Blackwell Publishing. - 1351-8216. ; 19:1, s. 76-81
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Tidskriftsartikel (refereegranskat)abstract
- The bleeding patterns of severe von Willebrand's disease (VWD) adversely affect quality of life, and may be life threatening. There is a presumed role for prophylaxis with VWF-containing concentrates, but data are scarce. The von Willebrand Disease Prophylaxis Network (VWD PN) was formed to investigate the role of prophylaxis in clinically severe VWD that is not responsive to other treatment(s). Using a retrospective design, the effect of prophylaxis was studied. Availability of records to document, or reliably assess, the type and frequency of bleeding episodes prior to, and after, the initiation of prophylaxis was required. Annualized bleeding rates were calculated for the period prior to prophylaxis, during prophylaxis and by primary bleeding indication defined as the site accounting for more than half of all bleeding symptoms. The Wilcoxon signed-rank test of differences in the medians was used. Sixty-one subjects from 20 centres in 10 countries were enrolled. Data for 59 were used in the analysis. The median age at onset of prophylaxis was 22.4 years. Type 3 VWD accounted for the largest number (N = 34, 57.6%). Differences in bleeding rates within individuals during compared with before prophylaxis were significant for the total group (P < 0.0001), and for those with primary bleeding indications of epistaxis (P = 0.0005), joint bleeding (P = 0.002) and GI bleeding (P = 0.001). The effect of prophylaxis was similar among those age < 18 years and those >= 18. One person developed an inhibitor during treatment. We conclude that prophylactic treatment of VWD is efficacious.
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| 4. |
- Ahnström, Josefin, et al.
(författare)
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A 6-year follow-up of dosing, coagulation factor levels and bleedings in relation to joint status in the prophylactic treatment of haemophilia
- 2004
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Ingår i: Haemophilia. - Blackwell Publishing. - 1351-8216. ; 10:6, s. 689-697
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Tidskriftsartikel (refereegranskat)abstract
- The primary aim of this study was to investigate the possible relationship between coagulation factor level and bleeding frequency during prophylactic treatment of haemophilia after stratification of the patients according to joint scores. The secondary aim was to obtain a systematic overview of the doses of coagulation factors prescribed for prophylaxis at the Malmo haemophilia treatment centre during a 6-year period. A retrospective survey of medical records for the years 1997-2002 and pharmacokinetic study results from the 1990s was complemented by collection of blood samples for coagulation factor assay when needed. Information on the dosing and plasma levels of factor VIII or factor IX, joint scores and incidence of bleedings (joint bleeds and 'other bleeds') was compiled. The patients were stratified by age (0-6, 7-12, 13-18, 19-36 and >36 years) and joint score (0, 1-6 and >6). Individual pharmacokinetic parameters of plasma coagulation factor activities (FVIII:C and FIX:C) were estimated. Trough levels during the treatment were calculated, as well as the number of hours per week of treatment during which plasma FVIII:C/FIX:C fell below a 1, 2 or 3% target level. Fifty-one patients with haemophilia A (two moderate, 49 severe) and 13 with haemophilia B (all severe) were included, yielding data for 364 patient-years of treatment. There was a wide range of dosing schedules, the most common ones being three times a week or every other day for FVIII and twice a week or every third day for FIX. The overall relationship between FVIII:C/FIX:C levels and incidence of joint bleeding was very weak, even after stratification of the patients according to joint score. There was no relationship between coagulation factor level and incidence of other bleeds. In this cohort of patients on high-dose prophylactic treatment, dosing was based more on clinical outcome in terms of bleeding frequency than on the aim to maintain a 1% target level of FVIII:C/FIX:C. Some patients did not bleed in spite of a trough level of <1% and others did in spite of trough levels >3%. The practical implication of our findings is that dosing in prophylactic treatment of haemophilia should be individualized. Thus, proposed standard regimens should be implemented only after careful clinical consideration, with a high readiness for re-assessment and individual dose tailoring.
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| 5. |
- Al-Shanqeeti, A, et al.
(författare)
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Protein Z and protein Z-dependent protease inhibitor - Determinants of levels and risk of venous thrombosis
- 2005
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Ingår i: Thrombosis and Haemostasis. - Schattauer. - 0340-6245. ; 93:3, s. 411-413
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Tidskriftsartikel (refereegranskat)abstract
- To assess the potential roles of protein Z (PZ) and protein Z-dependent protease inhibitor (ZPI) in venous thrombosis, their plasma levels were measured in 426 individuals with venous thrombosis and 471 control individuals participating in the Leiden Thrombophilia Study. A relationship between the level of PZ or ZPI and venous thrombosis was not detected in the overall case-control study. PZ and ZPI circulate as a complex and their plasma levels are interdependent. Both PZ and ZPI are increased with oral contraceptive use and reduced with oral anticoagulant therapy.
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| 6. |
- Astermark, Jan, et al.
(författare)
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A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor.
- 2007
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Ingår i: Blood. - American Society of Hematology. - 0006-4971. ; 109:Sep 21, s. 546-551
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Tidskriftsartikel (refereegranskat)abstract
- The development of inhibitory antibodies to factor VIII is a serious complication of hemophilia. FEIBA (factor VIII inhibitor-bypassing activity), an activated prothrombin complex concentrate (aPCC), and NovoSeven, recombinant factor Vila (rFVIIa), are used as hemostatic bypassing agents in treating patients with inhibitors. The FENOC study was designed to test equivalence of the products in the treatment of ankle, knee, and elbow joint bleeding. A prospective, open-label, randomized, crossover, equivalency design was used. The parameters of interest were the percentage of patients who reported efficacy in response to FEIBA and the percentage that reported efficacy in response to NovoSeven. A difference in these percentages of no more than 15% was determined to be a clinically acceptable magnitude for equivalence of the 2 products. The primary outcome was evaluation 6 hours after treatment. Data for 96 bleeding episodes contributed by 48 participants were analyzed. The criterion for declaring the 2 products equivalent at 6 hours was not met; however, the confidence interval of the difference in percentages of efficacy reported for each product only slightly exceeded the 15% boundary (-11.4%-15.7%), P=.059. FEIBA and NovoSeven appear to exhibit a similar effect on joint bleeds, although the efficacy between products is rated differently by a substantial proportion of patients. This trial was registered at www.clinicaltrials.gov as #NCT00166309.
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| 7. |
- Astermark, Jan, et al.
(författare)
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Anti- and procoagulant activities in factor VII-deficient subjects
- 2001
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Ingår i: Thrombosis research. - Pergamon-Elsevier Science Ltd. - 0049-3848. ; 101:6, s. 435-440
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Tidskriftsartikel (refereegranskat)abstract
- The clinical feature in patients with congenital factor VII deficiency is in part dependent on the underlying genetic defect, but the mechanisms influencing the genotype-phenotype correlation remain to be fully elucidated. In addition, thromboembolic events have been reported. Compensatory mechanisms involving vitamin K-dependent factors have been suggested. We have measured anticoagulant activities in 25 factor VII-deficient subjects (factor VII activity < or =36%) and 23 age-matched controls and correlated these to the vitamin K-dependent procoagulant activities. Two of the patients had a history of thromboembolism. The factor VII-deficient patients were found to have a significantly lower protein C activity than the controls 0.84 U/ml (95% CI 0.78; 0.89) vs. 0.98 U/ml (95% CI 0.91; 1.05), P=.004. In addition, the protein C activity was correlated to that of factor VII (r=.36; P=.014), factor IX (r=.45; P=.002) and factor X (r=.50; P=.0006), respectively. The level of prothrombin fragment 1+2 was correlated to the protein C (r=.40; P=.012) and to the factor VII activity (r=.42; P=.011). No differences between patients and controls were seen regarding total and free protein S, antithrombin, plasminogen activator inhibitor-1 (PAI-1) and tissue factor pathway inhibitor (TFPI). Seven of the patients were found to have the Factor V Leiden mutation, but none of them had experienced any thromboembolic event. The present data support the notion that compensatory hemostatic mechanisms might exist in that the protein C activity was found to be decreased in the factor VII-deficient subjects. Whether this could influence the clinical feature, including the risk of thromboembolic events in association with replacement therapy, remains to be evaluated.
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| 8. |
- 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: Br J Haematol. - Blackwell Publishing. - 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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| 9. |
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| 10. |
- Astermark, Jan, et al.
(författare)
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Arandomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study.
- 2009
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Ingår i: Gematologiya I Transfuziologiya. - Ministerstvo Zdravookhraneniya. - 0234-5730. ; 54:5, s. 35-
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Tidskriftsartikel (refereegranskat)abstract
- Arandomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study. J. Astermark(1), Sh. M. Donfield(2), D. M. DiMichele(3), A. Gringeri(4), S. A. Gilbert(2), J. Waters(2), E. Berntorp(1), for the FENOC Study Group. Department for Hematology and Coagulation Disorders, Malmo, University Hospital, Malmo, Sweden(1); Department of Biostatistics, Rho, Chapel Hill, NC2; Department of Pediatrics, Weill Medical College, Cornell University, New York, NY3; Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Italy(4). The development of inhibitory antibodies to factor VIII is a serious complication of hemophilia. FEIBA (factor VIII inhibitorbypassing activity), an activated prothrombin complex concentrate (aPCC), and NovoSeven, recombinant factor Vila (rFVIIa), are used as hemostatic bypassing agents in treating patients with inhibitors. The FENOC study was designed to test equivalence of the products in the treatment of ankle, knee, and elbow joint bleeding. A prospective, open-label, randomized, crossover, equivalency design was used. The parameters of interest were the percentage of patients who reported efficacy in response to FEIBA and the percentage that reported efficacy in response to NovoSeven. A difference in these percentages of no more than 15% was determined to be a clinically acceptable magnitude for equivalence of the 2 products. The primary outcome was evaluation 6 hours after treatment. Data for 96 bleeding episodes contributed by 48 participants were analyzed. The criterion for declaring the 2 products equivalent at 6 hours was not met; however, the confidence interval of the difference in percentages of efficacy reported for each product only slightly exceeded the 15% boundary (11.4-15.7%); p = 0.059. FEIBA and NovoSeven appear to exhibit a similar effect on joint bleeds, although the efficacy between products is rated differently by a substantial proportion of patients. This trial was registered at www.clinicaltrials.gov.
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