Biomedical subjects

Niamh M O'Connell

Publications and source records attributed to Niamh M O'Connell.

5 recordsLinked to original sources

PubMed2006

The value of autofluorescence as a diagnostic feature of acute promyelocytic leukemia.

Autofluorescence is an immunophenotypic characteristic of leukemic blasts in acute promyelocytic leukemia (APL). We examined the fluorescent intensity of isotype controls in 25 cases of APML and 25 controls with acute myeloid leukemia. The fluorescence of the FITC- and PE-conjugated controls was consistently higher in APML. Autofluorescence may therefore represent a helpful diagnostic marker in APML.

Blast Crisis↗

PubMed2005

Factor XI deficiency database: an interactive web database of mutations, phenotypes, and structural analysis tools.

Factor XI (FXI) is the zymogen of a serine protease enzyme in the intrinsic pathway of blood coagulation and is an important factor in the creation of a stable fibrin clot. Deficiency of FXI leads to an injury-related bleeding disorder and is remarkable for the lack of correlation between bleeding symptoms and FXI coagulant activity (FXI:C). The FXI protein is composed of five domains: four tandem repeat domains of approximately 80 residues known as Apple (Ap) domains, and the catalytic serine protease (Sp) domain. A total of 65 mutations throughout the FXI gene (F11) have been reported in FXI deficient patients. An interactive web database of these mutations has been created (www.FactorXI.org) that integrates the phenotypic data with genetic data and structural homology models for the five FXI domains. The database provides a central repository for all reported genetic alterations within F11. With the use of recently developed visualization tools, each mutation can be highlighted on the structural models of the FXI domains together with an appropriate survey of patient data, such as FXI:C levels and FXI antigen levels. The database also enables new F11 mutations to be interpreted. The interactive design of this database will lead to a more comprehensive comparative understanding of the genetic factors that influence bleeding risk.

DNA Mutational Analysis↗

PubMed2003

Recombinant FVIIa in the management of uncontrolled hemorrhage.

BACKGROUND: Recombinant FVIIa (rFVIIa/NovoSeven) is a novel hemostatic agent originally developed to treat patients with hemophilia who had developed inhibitors. Several case reports have suggested that rFVIIa may be effective in treating patients without a pre-existing bleeding disorder who have uncontrolled bleeding. STUDY DESIGN AND METHODS: Data on the efficacy and safety of rFVIIa in the treatment of massive hemorrhage were obtained retrospectively from the NovoSeven extended-use data collection system. RESULTS: A total of 40 patients received rFVIIa for uncontrolled bleeding, and in these patients, bleeding stopped or decreased in 32 (80%). Blood product usage was significantly decreased after rFVIIa administration. Thromboembolic events occurred in three patients with additional risk factors for thrombosis. Of 40 patients, 23 (57.5%) died. Bleeding was the direct cause of death in seven cases (all within 24 hr of administration of rFVIIa). The remaining 16 deaths were the result of sepsis, multi-organ failure, or the underlying disease. CONCLUSIONS: In this retrospective study of data voluntarily submitted to a web-based drug surveillance program, we present preliminary results on the use of rFVIIa in nonhemophilia patients with bleeding. Although some efficacy is suggested, there was a high mortality rate from nonhemorrhagic causes. Randomized controlled trials are needed to properly assess the role of rFVIIa in the management of hemorrhage.

Adult↗

PubMed2003

Analysis and results of the recombinant factor VIIa extended-use registry.

This paper describes the analysis of recombinant factor VIIa (rFVIIa; NovoSeven; Novo Nordisk, Bagsvaerd, Denmark) use in 40 patients with intractable bleeding in the UK. All cases were reported on the 'rFVIIa extended use database' (Traumanet) between its launch in February 1999 and 12 March 2002. Twenty-one other cases reporting rFVIIa use in different circumstances were excluded from the analysis. Recombinant FVIIa was effective in stopping or markedly reducing blood loss in 80% of patients; 20% of patients did not respond to treatment. Non-responders tended to have more deranged coagulation and lower platelet counts compared with responders. Despite a wide range of underlying illnesses, including malignancy and sepsis, few patients suffered adverse events. Thrombotic events occurred in three of 40 (7.5%) patients and these patients were considered as already at risk of thrombosis from other causes. The data suggest that rFVIIa is safe and effective therapy in patients with uncontrollable haemorrhage.

Adult↗

PubMed2003

Factor XI deficiency--from molecular genetics to clinical management.

Factor XI (FXI) deficiency is a rare bleeding disorder, but is known to occur more frequently in a number of well-defined populations. FXI deficiency is most notable for its variable clinical phenotype. The FXI gene is located at the distal end of the long arm of chromosome 4 and encodes a 607 amino acid mature protein, which is a zymogen for a serine protease. Although the serine protease domain is similar to that of many other coagulation factors, the heavy chain differs in that it contains four tandem Apple domains. FXI is also unique in that it exists as a homodimer, with this dimerization appearing essential for normal function. A total of 39 different FXI mutations have been identified to date, affecting both the catalytic and Apple domains. This article will review the molecular genetics of FXI deficiency with particular focus on the implications of these findings for the clinical management of this condition. The potential utility of alternatives to plasma-derived FXI concentrate, such as recombinant factor VIIa (rFVIIa, NovoSeven) will also be explored.

Amino Acid Sequence↗