ABSTRACT
Haemophilia A individuals displaying a similar genetic defect have heterogeneous clinical phenotypes. Our objective was to evaluate the underlying effect of exogenous factor (f)VIII on tissue factor (Tf)-initiated blood coagulation in severe haemophilia utilizing both empirical and computational models. We investigated twenty-five clinically severe haemophilia A patients. All individuals were on fVIII prophylaxis and had not received fVIII from 0.25 to 4 days prior to phlebotomy. Coagulation was initiated by the addition of Tf to contact-pathway inhibited whole blood ± an anti-fVIII antibody. Aliquots were quenched over 20 min and analyzed for thrombin generation and fibrin formation. Coagulation factor levels were obtained and used to computationally predict thrombin generation with fVIII set to either zero or its value at the time of the draw. As a result of prophylactic fVIII, at the time of the blood draw, the individuals had fVIII levels that ranged from <1% to 22%. Thrombin generation (maximum level and rate) in both empirical and computational systems increased as the level of fVIII increased. FXIII activation rates also increased as the fVIII level increased. Upon suppression of fVIII, thrombin generation became comparable in both systems. Plasma composition analysis showed a negative correlation between bleeding history and computational thrombin generation in the absence of fVIII. Residual prophylactic fVIII directly causes an increase in thrombin generation and fibrin cross-linking in individuals with clinically severe haemophilia A. The combination of each individual's coagulation factors (outside of fVIII) determine each individual's baseline thrombin potential and may affect bleeding risk.
Subject(s)
Factor VIII/administration & dosage , Hemophilia A/drug therapy , Adolescent , Adult , Blood Coagulation/drug effects , Blotting, Western , Cohort Studies , Computer Simulation , Factor VIII/analysis , Factor VIII/pharmacology , Humans , Regression Analysis , Thrombin/biosynthesis , Young AdultABSTRACT
BACKGROUND: The role of the dietetic support worker (DSW) was developed to provide cost-effective support to dietetic services in the National Health Service (NHS). However, there is little evidence about how the role is perceived or the impact of the introduction of Agenda for Change in 2004 (a guide to pay terms and conditions for NHS staff) on role definition. The present study aimed to gather evidence from DSWs and dietitians on the current role of the DSW to help inform the future development of the role. METHODS: A questionnaire survey was conducted on DSWs and dietitians in 10 trusts in the East of England. Issues included qualifications, experience, training, satisfaction with Agenda for Change, supervision and responsibility. Themes were further explored by semi-structured telephone interviews conducted on a subsample. RESULTS: Eighteen out of 24 DSWs and 62 out of 98 dietitians responded to the questionnaire. The role of the DSW is highly valued by dietitians. Over three-quarters of DSWs and over 90% of dietitians agree that the employment of DSWs improved the working lives of dietitians. Only 50% of DSWs were happy with their Agenda for Change banding, although this did not adversely affect their job satisfaction. Both groups saw the role of the DSW becoming more specialised, despite concerns about access to appropriate training and the lack of a structured career pathway. CONCLUSIONS: This study identified issues relating to the future development of the role of the DSW from the viewpoint of DSWs and dietetic assistants.