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- Antonarakis, S. E., et al.
(författare)
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Factor VIII gene inversions in severe hemophilia A : Results of an international consortium study
- 1995
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 86:6, s. 2206-2212
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Tidskriftsartikel (refereegranskat)abstract
- Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells ware observed among 225 cases (≃ 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).
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3. |
- Clausen, Niels, et al.
(författare)
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Similar bleeding phenotype in young children with haemophilia A or B : A cohort study
- 2014
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 20:6, s. 747-755
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Tidskriftsartikel (refereegranskat)abstract
- The bleeding phenotype has been suggested to differ between haemophilia A and B. More knowledge on the bleeding phenotype at initiation of treatment is important to optimize patient care. The aim of this study was to investigate the severity of the bleeding phenotype and the variation in bleeding in children with severe or moderate haemophilia A and B. Consecutive, previously untreated patients with severe or moderate haemophilia A and B (factor VIII or IX activity <0.01 or 0.01-0.05 IU mL-1 respectively) born between January 1st 2000 and January 1st 2010 were included. Primary outcome was severity of bleeding tendency. Secondary outcome was variation in bleeding pattern. A total of 582 patients with severe haemophilia A and 76 with severe haemophilia B did not differ in age at first exposure to clotting factor (0.81 vs. 0.88 years, P = 0.20), age at first bleed (0.82 vs. 0.88 years, P = 0.36), and age at first joint bleed (1.18 vs. 1.20 years, P = 0.59). Patients with moderate haemophilia were older compared to patients with severe haemophilia. In patients with moderate haemophilia there were no clear differences between haemophilia A and B. Severity and variation in bleeding phenotype are similar during the early stage of treatment in patients with severe and moderate haemophilia A and B respectively. The findings imply that children with haemophilia B should be observed and treated as vigilantly as those with haemophilia A.
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- Astermark, J., et al.
(författare)
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Symposium in memory of Professor Inga Marie Nilsson
- 2001
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 7:4, s. 401-410
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Konferensbidrag (refereegranskat)abstract
- Professor Inga Marie Nilsson (1923-99) was a pioneer in the field of bleeding and thrombo-embolic disorders and made several major scientific contributions during her career. To honour her memory, colleagues from all over the world were invited to cover several aspects of haemostasis by giving state-of-the-art lectures at an international symposium in Malmö on September 22-23, 2000, chaired by Professors Lou Aledort and Erik Berntorp. Colleagues of Professor Nilsson in Malmö gave a short introduction to each topic. A short review of the meeting will be presented.
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6. |
- Hoots, W. K., et al.
(författare)
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Secondary prophylaxis with recombinant activated factor VII improves health-related quality of life of haemophilia patients with inhibitors
- 2008
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 14:3, s. 466-466
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Tidskriftsartikel (refereegranskat)abstract
- Haemophilia patients with inhibitors characteristically have impaired joint function and reduced health-related quality of life (HRQoL). This analysis examined whether secondary prophylaxis with recombinant activated factor VII (rFVIIa) improves HRQoL vs. conventional on-demand therapy in patients with haemophilia with inhibitors and frequent bleeds. After a 3-month preprophylaxis period, 22 patients received daily rFVIIa prophylaxis (90 or 270 mu g kg(-1)) for 3 months, followed by 3 months' postprophylaxis. Days of hospitalization, absence from school/work and mobility aids requirements were recorded. HRQoL was assessed by EuroQoL (EQ-5D) questionnaire, visual analogue scale (VAS), derived Time to Trade-Off (TTO) scores and Quality Adjusted Life Years (QALYs). rFVIIa prophylaxis significantly (P < 0.0001) reduced bleeding frequency vs. prior on-demand therapy. Hospitalization (5.9% vs. 13.5%; P = 0.0026) and absenteeism from school/work (16.7% vs. 38.7%; P = 0.0127) decreased during prophylaxis; these effects tended to be maintained during postprophylaxis. HRQoL (evaluated by EQ-5D) tended to improve during and after rFVIIa prophylaxis. Notably, pain decreased and mobility increased in 40.9% and 27.3% of patients, respectively, at the end of the postprophylaxis period vs. preprophylaxis. Median VAS score increased from 66 to 73 (P = 0.048), and TTO scores suggested better HRQoL (0.62 vs. 0.76; P = 0.054) during postprophylaxis than preprophylaxis. Small to moderate changes in effect sizes were reported for VAS and TTO scores. Median QALYs were 0.68 (VAS) and 0.73 (TTO). Reductions in bleeding frequency with secondary rFVIIa prophylaxis were associated with improved HRQoL vs. on-demand therapy.
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8. |
- Halldén, Christer, 1957-, et al.
(författare)
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Investigation of disease-associated factors in haemophilia A patients without detectable mutations
- 2012
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Ingår i: Haemophilia. - : Blackwell. - 1351-8216 .- 1365-2516. ; 18:3, s. e132-e137
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Tidskriftsartikel (refereegranskat)abstract
- To investigate disease causing mechanism in haemophilia A patients without detectable mutation. Screening for F8 mutations in 307 haemophilia A patients using: re-sequencing and inversion PCR, reverse transcription (RT-PCR) of mRNA, MLPA analysis, haplotyping using SNP and microsatellite markers. No F8 mutations were detected in 9 of the 307 patients (2.9%) using re-sequencing and inversion PCR. MLPA analysis detected duplication in exon 6 in one patient and RT-PCR showed no products for different regions of mRNA in four other patients, indicating failed transcription. No obvious associations were observed between the phenotypes of the nine patients, their F8 haplotypes and the putative mutations detected. The mutation-positive patients carrying the same haplotypes as the mutation-negative patients show a multitude of different mutations, emphasizing the lack of associations at the haplotype level. VWF mutation screening and factor V measurements ruled out type 2N VWD and combined factor V and VIII deficiency respectively. To further investigate a possible role for FVIII interacting factors the haplotypes/diplotypes of F2, F9, F10 and VWF were compared. The nine patients had no specific haplotype/diplotype combination in common that can explain disease. Duplications and faulty transcription contribute to the mutational spectrum of haemophilia A patients where conventional mutation screening fail to identify mutations.
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9. |
- Lee, C A, et al.
(författare)
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Prophylactic treatment in Sweden - Overtreatment or optimal model?
- 1998
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 4:4, s. 409-412
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Tidskriftsartikel (refereegranskat)abstract
- At the haemophilia centre in Malmo, Sweden, regular prophylactic treatment is begun at 1-1 1/4 years of age, before the onset of joint bleeds. The dose and dose interval are optimised by means of pharmacokinetic studies to determine the individual patient's FVIII or IX metabolism, the goal of maintaining a level > 1% of normal being taken as a guideline which experience has shown to yield satisfactory control of bleeding diathesis. An optimal model for prophylactic treatment needs to be applicable to haemophiliacs and acceptable to health authorities in a majority of the countries in the world. To fulfill these criteria, the Swedish model, which has been shown to yield most satisfactory outcome, can hopefully be further refined in the future. Were continuous infusion, using a recombinate concentrate with a prolonged half-life, technically feasible and socially acceptable to the child, we would probably have attained the optimal model of prophylactic treatment.
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10. |
- Graham, J B, et al.
(författare)
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Carrier detection in hemophilia A : a cooperative international study. I. The carrier phenotype
- 1986
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Ingår i: Blood. - 0006-4971. ; 67:6, s. 9-1554
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Tidskriftsartikel (refereegranskat)abstract
- Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non-O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.
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