Haemophilic Arthropathy and the role of Extracellular Histones-V1
Research type
Research Study
Full title
Haemophilic Arthropathy and the role of Extracellular Histones\nAn early translational approach towards preventing haemophilic arthropathy\n
IRAS ID
138051
Contact name
Cheng-Hock Toh
Contact email
Sponsor organisation
University of Liverpool
Research summary
Haemophilia A is a hereditary genetic disorder characterized by deficiency of a clotting factor called factor eight (VIII) which normally controls blood clotting by forming a temporary clot (scab) to stop bleeding when a blood vessel is broken. However, due to the deficiency of factor VIII in haemophilia, clot formation is delayed which results in prolonged bleeding. In severe cases (very low levels of factor VIII), there is an increased tendency for bleeding into joints “haemarthrosis”, which is often associated with severe pain, swelling, disfigurement and gradual destruction of the joint components and development of a debilitating condition known as “haemophilic arthropathy - HA”. HA is considered the leading cause of morbidity in severe haemophiliacs. Although the main trigger for joint changes in HA is the joint bleeds, the exact sequence of events that lead to joint destruction are not well known. \n“Histones”, a group of proteins which reside within the nucleus of cells, are known to be released outside the cells upon cellular damage “extracellular histones”. Recent studies have provided compelling evidence that extracellular histones are highly toxic to various mammalian cells and have been implicated as contributors to the development of several conditions including inflammation, trauma and cancer. This study aims to illustrate the potential contribution of extracellular histones to the development and progression of HA following joint bleeds which could lead to new therapeutic interventions for this debilitating condition. \nIn this project, we aim to obtain blood and joint tissue samples from patients with haemophilia who are undergoing a surgical procedure (either arthroscopic procedures such as a synovectomy or an open procedure such as a joint replacement) for joint arthropathy. Blood and joint tissue samples will also be obtained from aged-match patients with no haemophilia undergoing similar orthopaedic operations as controls.
REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
14/EE/0049
Date of REC Opinion
23 Jan 2014
REC opinion
Favourable Opinion