TABI
Research type
Research Study
Full title
TABI: Thrombin Generation Assay to predict the efficacy of Bypassing agents in Haemophilia Patients with Inhibitors
IRAS ID
179515
Contact name
Ruth Pink
Contact email
Sponsor organisation
Hampshire Hospitals NHS Foundation Trust
Duration of Study in the UK
1 years, 6 months, 1 days
Research summary
Over the past two decades, the introduction of coagulation factor replacement has revolutionised the care of patients with Haemophilia A by preventing and treating bleeding episodes. As a result these patients have near normal life expectancy and improved quality of life.
The main complication of coagulation factor replacement is the development of antibodies (inhibitors) towards coagulation factor FVIII. It can occur in up to 30% of patients with severe haemophilia A. The treatment of haemophilia patients with inhibitors is difficult, as they no longer respond to coagulation factor replacement.
Bypassing agents with activated prothrombin complex concentrate (aPCC) and recombinant Factor VIIa (rFVIIa) have shown to be successful in managing bleeding in haemophilia patients with inhibitors.
However the lack of direct laboratory assay to monitor and predict the response of the bypassing agents can render the clinical management of these patients challenging. In patients without inhibitors, FVIII levels are measured to monitor FVIII replacement therapy to ensure a safe haemostatic level is achieved during a bleeding episode. FVIII monitoring is however not useful in patients with inhibitors on bypassing therapy as the bypassing agents generate clot stability independently of FVIII.
In addition, studies have show that when patients are treated both aPCC and rFVIIa, over one third of patients demonstrate a greater efficacy towards one bypassing agent over another. Therefore it is imperative to individualise bypassing treatment.
Thrombin generation testing is a global haemostatic assay, which can predict the response of bypassing agents. However the test lacks standardisation and thus more research is needed before routine clinical use.
We are proposing a multicentre study to develop a laboratory technique to monitor and predict the efficacy of bypassing agents for each individual haemophilia patient with inhibitor. This laboratory method in turn can be used to develop an individualised approach to bypassing product treatment in haemophilia A with inhibitors.REC name
South Central - Berkshire B Research Ethics Committee
REC reference
15/SC/0277
Date of REC Opinion
29 Apr 2015
REC opinion
Favourable Opinion