Start of UK Confidential Haemophilia A Database: Analysis of 142 Patients by Solid Phase Fluorescent Chemical Cleavage of Mismatch

1999 ◽  
Vol 81 (06) ◽  
pp. 900-905 ◽  
Author(s):  
Naushin Waseem ◽  
Richard Bagnall ◽  
Peter Green ◽  
Francesco Giannelli ◽  
Keyword(s):  
Factor Viii ◽  
Solid Phase ◽  
Haemophilia A ◽  
National Strategy ◽  
Coding Region ◽  
Database Analysis ◽  
Chemical Cleavage ◽  
Signal Region ◽  
The Uk ◽  
Von Willebrand

SummaryA national strategy for optimising genetic services in haemophilia A has been initiated in the UK. Solid phase fluorescent chemical cleavage of mismatch is used to screen the entire coding region of factor VIII in six segments: four amplified from the trace of mRNA in blood lymphocytes and two from genomic DNA for the 3.4 kb exon 14 and flanking intron sequences. These segments are analysed in two threefold multiplexes so that the genes of 18 patients can be screened in a single ABI 377 gel. The promoter and polyadenylation signal region are amplified and sequenced directly. We have analysed 142 unrelated patients and identified 141 factor VIII mutations and one Normandy type von Willebrand homozygote. The former mutations include 89 missense, 10 nonsense, 5 frameshift, one 24 bp deletion and one splice signal defect. These comprise 71 different changes, of which 39 have not been previously observed.

scholarly journals Desmopressin treatment combined with clotting factor VIII concentrates in patients with non-severe haemophilia A: protocol for a multicentre single-armed trial, the DAVID study

BMJ Open ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. e022719 ◽  
Author(s):  
Lisette M Schütte ◽  
Marjon H Cnossen ◽  
Reinier M van Hest ◽  
Mariette H E Driessens ◽  
Karin Fijnvandraat ◽  
...  
Keyword(s):  
Factor Viii ◽  
Combination Treatment ◽  
Bleeding Risk ◽  
Clotting Factor ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Registration Number ◽  
Concentrate Treatment ◽  
Factor Viii Concentrates ◽  
Von Willebrand

IntroductionHaemophilia A is an inherited bleeding disorder characterised by factor VIII (FVIII) deficiency. In patients with non-severe haemophilia A, surgery and bleeding are the main indications for treatment with FVIII concentrate. A recent study reported that standard dosing frequently results in FVIII levels (FVIII:C) below or above FVIII target ranges, leading to respectively a bleeding risk or excessive costs. In addition, FVIII concentrate treatment carries a risk of development of neutralising antibodies. An alternative is desmopressin, which releases endogenous FVIII and von Willebrand factor. In most patients with non-severe haemophilia A, desmopressin alone is not enough to achieve FVIII target levels during surgery or bleeding. We hypothesise that combined pharmacokinetic (PK)-guided administration of desmopressin and FVIII concentrate may improve dosing accuracy and reduces FVIII concentrate consumption.Methods and analysisIn the DAVID study, 50 patients with non-severe haemophilia A (FVIII:C ≥0.01 IU/mL) with a bleeding episode or undergoing surgery will receive desmopressin and FVIII concentrate combination treatment. The necessary dose of FVIII concentrate to reach FVIII target levels after desmopressin administration will be calculated with a population PK model. The primary endpoint is the proportion of patients reaching FVIII target levels during the first 72 hours after start of the combination treatment. This approach was successfully tested in one pilot patient who received perioperative combination treatment.Ethics and disseminationThe DAVID study was approved by the medical ethics committee of the Erasmus MC. Results of the study will be communicated trough publication in international scientific journals and presentation at (inter)national conferences.Trial registration numberNTR5383; Pre-results.

scholarly journals Influence of blood group, von Willebrand factor levels, and age on factor VIII levels in non‐severe haemophilia A

2020 ◽  
Vol 18 (5) ◽  
pp. 1081-1086
Author(s):  
Judit Rejtő ◽  
Oliver Königsbrügge ◽  
Ella Grilz ◽  
Stefanie Hofer ◽  
Lisa‐Marie Mauracher ◽  
...  
Keyword(s):  
Factor Viii ◽  
Blood Group ◽  
Von Willebrand Factor ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Von Willebrand ◽  
Willebrand Factor

Spectrum of causative mutations in patients with haemophilia A in Austria

2010 ◽  
Vol 104 (07) ◽  
pp. 78-85 ◽  
Author(s):  
Sylvia Reitter ◽  
Rümuth Sturn ◽  
Birgit Horvath ◽  
Renate Freitag ◽  
Christoph Male ◽  
...  
Keyword(s):  
Ethnic Diversity ◽  
Risk Estimation ◽  
Low Frequency ◽  
Clinical Information ◽  
Haemophilia A ◽  
Italian Population ◽  
Coding Region ◽  
Double Mutation ◽  
Sequencing Part ◽  
The Uk

SummaryIn patients with haemophilia A knowledge of the pathogenetic mutation is important i) as basis for carrier diagnosis and ii) for risk estimation of inhibitor formation. The pathogenetic mutations were identified by testing inversions in intron 1 and 22 (IVS22 and IVS1) and sequencing part of the promoter, the coding region and the exon/intron boundaries in a cohort of Austrian haemophilia A patients. A total of 239 patients from nine participating centres, who had consented to genetic testing and of whom clinical information was available were included in the study. First, IVS22 and IVS1 were tested; in case of absence of either inversion patients were subjected to sequencing. Mutations within the FVIII gene were identified in 234 patients. Notably, 53 mutations had not previously been described in HAMSTeRS. Of our patient cohort, 72.5 % had either an IVS22 or a missense mutation. Interestingly, in three brothers with severe haemophilia, we found a double mutation in exon 14 (missense + small deletion). The spectrum of mutations in Austrian haemophilia A patients was comparable to that found in the German and Italian population; however, it differed from the spectrum reported in the UK. In conclusion, 53 not previously published mutations were identified in Austrian haemophilia A patients. The occurrence of double mutations in the factor VIII gene could be confirmed and their low frequency was corroborated. We speculate that the differences between mutations in Austria and other European countries are due to ethnic diversity. Detailed investigations of the association of ethnicity and the mutation spectrum are planned.

scholarly journals Clinical assessment of Optivate®, a high-purity concentrate of factor VIII with von Willebrand factor, in the management of patients with haemophilia A

Haemophilia ◽  
2011 ◽  
Vol 17 (3) ◽  
pp. 456-462 ◽  
Author(s):  
A. DMOSZYNSKA ◽  
K. KULICZKOWSKI ◽  
A. HELLMANN ◽  
J. TRELINSKI ◽  
J. KLOCZKO ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Clinical Assessment ◽  
High Purity ◽  
Haemophilia A ◽  
Von Willebrand ◽  
Willebrand Factor
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